RESUMO

Abstract The renin-angiotensin-aldosterone system (RAAS) plays a key role in diabetic nephropathy (DN). Angiotensin-II secreted during the RAAS pathway increases nephropathy. It stimulates oxidative stress which can quench nitric oxide. Reduced nitric oxide level aggravates Ang-II-induced vasoconstriction. Ang-II has also emerged as a central mediator of the glomerular hemodynamic changes that are associated with renal injury. Deletion of ACE2 is also noted due to increased Ang-II level which leads to the development of DN. We hypothesize that nephropathy caused by Ang-II in the periphery may be controlled by brain RAAS. ACE inhibitors and ARBs may show the renoprotective effect when administered through ICV without crossing the blood-brain barrier. DN was observed after 8 weeks of diabetes induction through alloxan. Administration of captopril and valsartan once and in combined therapy for 2 weeks, significantly reduced urine output, blood urea nitrogen, total protein in the urine, serum cholesterol, serum creatinine, serum triglycerides, and kidney/body weight ratio as compared to diabetic control rats. Further, combination therapy significantly increased the body weight and serum nitrate level as compared to diabetic control animals. However, increased ACE2 levels in the brain may reduce the sympathetic outflow and might have decreased the peripheral activity of Ang-II which shows beneficial effects in DN.

Assuntos

Animais , Masculino , Feminino , Ratos , Sistema Renina-Angiotensina/imunologia , Angiotensina II/análise , Nefropatias Diabéticas/patologia , Ferimentos e Lesões/classificação , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Peptidil Dipeptidase A/administração & dosagem

RESUMO

BACKGROUND: In healthy pregnancies, components of the Renin-Angiotensin system (RAS) are present in the placental villi and contribute to invasion, migration, and angiogenesis. At the same time, soluble fms-like tyrosine kinase 1 (sFlt-1) production is induced after binding of ANG-II to its receptor (AT-1R) in response to hypoxia. As RAS plays an essential role in the pathogenesis of COVID-19, we hypothesized that angiogenic marker (sFlt-1) and RAS components (ANG-II and ACE-2) may be related to adverse outcomes in pregnant women with COVID-19; Methods: Prospective cohort study. Primary outcome was severe pneumonia. Secondary outcomes were ICU admission, intubation, sepsis, and death. Spearman's Rho test was used to analyze the correlation between sFlt-1 and ANG-II levels. The sFlt-1/ANG-II ratio was determined and the association with each adverse outcome was explored by logistic regression analysis and the prediction was assessed using receiver-operating-curve (ROC); Results: Among 80 pregnant women with COVID-19, the sFlt-1/ANG-II ratio was associated with an increased probability of severe pneumonia (odds ratio [OR]: 1.31; p = 0.003), ICU admission (OR: 1.05; p = 0.007); intubation (OR: 1.09; p = 0.008); sepsis (OR: 1.04; p = 0.008); and death (OR: 1.04; p = 0.018); Conclusion: sFlt-1/ANG-II ratio is a good predictor of adverse events such as pneumonia, ICU admission, intubation, sepsis, and death in pregnant women with COVID-19.

Assuntos

Angiotensina II/metabolismo , COVID-19/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto , Angiotensina II/análise , Angiotensina II/fisiologia , Biomarcadores , COVID-19/complicações , Estudos de Coortes , Estado Terminal , Feminino , Humanos , México/epidemiologia , Placenta/metabolismo , Pré-Eclâmpsia , Gravidez , Gestantes , Estudos Prospectivos , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/análise , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/fisiologia

RESUMO

ABSTRACT Purpose: Pseudoexfoliation syndrome has been linked to impaired function of the heart and blood vessels. We conducted a study to investigate the role of the renin-angiotensin system in the etiopathogenesis of pseudoexfoliation syndrome. Methods: The subjects were 14 patients with pseudoexfoliation syndrome and 14 healthy controls who underwent cataract extraction. Preoperative 5-ml samples of peripheral venous blood and perioperative aqueous humor were collected from the patients in both groups. Plasma and aqueous humor renin levels were analyzed by an immunoradiometric method, and angiotensin II levels were analyzed by radioimmunassay. SPSS version 16.0 was used for statistical analyses. A p-value <0.05 was considered to indicate a statistically significant difference. Results: The mean ages of the patients in pseudoexfoliation and control groups were 71.7 ± 7.1 and 67.4 ± 9.3 years, respectively (p=0.140). The median aqueous humor renin level was 7.73 pg/ml (4.15-21) in the control group and 11.95 pg/ml (3.75-18.54) in pseudoexfoliation group (p=0.022). There were no differences between the two groups in the plasma renin, plasma angiotensin II, or aqueous humor angiotensin II levels. The correlations between plasma and aqueous humor renin levels and between plasma and aqueous humor angiotensin II levels were examined separately for each group; no significant correlations were observed in pseudoexfoliation group (r=-0.440, p=0.115; r=-0.414, p=0.142) or the control group (r=-0.232, p=0.425; r=0.482, p=0.081). Conclusion: Aqueous humor renin levels are higher in pseudoexfoliation syndrome. The results indicate a probable role of renin-angiotensin system in pseudoexfoliation syndrome. Further studies with larger numbers of cases are needed to clarify the precise association of renin-angiotensin system with the etiopathogenesis of pseudoexfoliation syndrome.

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RESUMO Objetivo: A síndrome de pseudo-exfoliação tem sido associada ao comprometimento da função do coração e dos vasos sanguíneos. Foi realizado um estudo para investigar o papel do sistema renina-angiotensina na etiopatogenia da síndrome de pseudo-exfoliação. Métodos: Os sujeitos foram 14 pacientes com síndrome de pseudo-exfoliação e 14 controles saudáveis submetidos à extração de catarata. Amostras pré-operatórias de 5 ml de sangue venoso periférico e humor aquoso perioperatório foram coletadas dos pacientes em ambos os grupos. Os níveis de renina no plasma e humor aquoso foram analisados pelo método imunorradiométrico e os níveis de angiotensina II foram analisados por radioimunoensaio. O SPSS versão 16.0 foi utilizado para análises estatísticas. Considerou-se o valor de p<0,05 para indicar uma diferença estatisticamente significativa. Resultados: A média de idade dos pacientes nos grupos pseudo-exfoliação e controle foi de 71,7 ± 7,1 e 67,4 ± 9,3 anos, respectivamente (p=0,140). O nível médio de renina no humor aquoso foi de 7,73 pg / ml (4,15-21) no grupo controle e 11,95 pg/ml (3,75-18,54) no grupo pseudo-exfoliação (p=0,022). Não houve diferenças entre os dois grupos de renina plasmática, angiotensina II plasmática ou nos níveis de angiotensina II em humor aquoso. As correlações entre os níveis de renina no plasma e no humor aquoso e entre os níveis de angiotensina II no plasma e humor foram examinadas separadamente para cada grupo; n]ao foram observadas correlações significativas no grupo pseudo-exfoliação (r=-0,440, p=0,115; r=-0,414, p=0,142) ou no grupo controle (r=-0,232, p=0,425; r=0,482, p=0,081). Conclusão: Os níveis de renina no humor aquoso são mais elevados na síndrome de pseudo-exfoliação. Os resultados indicam um provável papel do sistema renina-angiotensina na síndrome de pseudo-exfoliação. Novos estudos com maior número de casos são necessários para esclarecer a associação precisa do sistema renina-angiotensina com a etiopatogenia da síndrome de pseudo-exfoliação.

Assuntos

Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Sistema Renina-Angiotensina , Angiotensina II/análise , Renina/análise , Síndrome de Exfoliação/etiologia , Humor Aquoso/metabolismo , Catarata/sangue , Extração de Catarata , Estudos Prospectivos , Síndrome de Exfoliação/metabolismo , Síndrome de Exfoliação/sangue , Período Pré-Operatório

RESUMO

Preeclampsia is characterized by an increased sensitivity to angiotensin II (Ang II). We herein assessed whether serum Ang II levels measured by a new developed bioassay are associated with preeclampsia, its severity, and the risk for developing this disease.Using a cross-sectional design, we studied 90 pregnant women (30 healthy pregnant and 60 with preeclampsia [30 with- and 30 without severe features]). We also used a nested case-control study with 30 women who eventually developed preeclampsia and 31 normotensive controls. Serum samples were collected at diagnosis of preeclampsia or at 4-week intervals (from weeks 12th to 36th). Ang II was measured using a bioassay.At diagnosis of preeclampsia, serum Ang II concentrations were significantly lower in preeclampsia without and with severe features (P = .001 and P < .001, respectively) than in healthy pregnancy. In addition, Ang II was different in preeclampsia with severe features than in those without severe features (P = .048). Women who subsequently developed preeclampsia had lower Ang II levels than women with normal pregnancies, and these changes became significant at 24 weeks onward. The risk to developing preeclampsia was higher among women with Ang II concentration values in the lowest quartile of the control distribution from 12 weeks onward (odds ratio ranging from 3.8 [95% CI 1.3-11.1] to 6.5 [95% CI 1.6-26.9]).We concluded that concentrations of Ang II are markedly diminished at diagnosis of preeclampsia and are closely associated with the severity of disease. Changes in circulating levels of Ang II precede the clinical presentation of preeclampsia.

Assuntos

Angiotensina II , Pré-Eclâmpsia , Adulto , Angiotensina II/análise , Angiotensina II/sangue , Bioensaio/métodos , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , México , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Valor Preditivo dos Testes , Gravidez , Reprodutibilidade dos Testes , Medição de Risco/métodos , Índice de Gravidade de Doença , Estatística como Assunto

RESUMO

PURPOSE: Pseudoexfoliation syndrome has been linked to impaired function of the heart and blood vessels. We conducted a study to investigate the role of the renin-angiotensin system in the etiopathogenesis of pseudoexfoliation syndrome. METHODS: The subjects were 14 patients with pseudoexfoliation syndrome and 14 healthy controls who underwent cataract extraction. Preoperative 5-ml samples of peripheral venous blood and perioperative aqueous humor were collected from the patients in both groups. Plasma and aqueous humor renin levels were analyzed by an immunoradiometric method, and angiotensin II levels were analyzed by radioimmunassay. SPSS version 16.0 was used for statistical analyses. A p-value <0.05 was considered to indicate a statistically significant difference. RESULTS: The mean ages of the patients in pseudoexfoliation and control groups were 71.7 ± 7.1 and 67.4 ± 9.3 years, respectively (p=0.140). The median aqueous humor renin level was 7.73 pg/ml (4.15-21) in the control group and 11.95 pg/ml (3.75-18.54) in pseudoexfoliation group (p=0.022). There were no differences between the two groups in the plasma renin, plasma angiotensin II, or aqueous humor angiotensin II levels. The correlations between plasma and aqueous humor renin levels and between plasma and aqueous humor angiotensin II levels were examined separately for each group; no significant correlations were observed in pseudoexfoliation group (r=-0.440, p=0.115; r=-0.414, p=0.142) or the control group (r=-0.232, p=0.425; r=0.482, p=0.081). CONCLUSION: Aqueous humor renin levels are higher in pseudoexfoliation syndrome. The results indicate a probable role of renin-angiotensin system in pseudoexfoliation syndrome. Further studies with larger numbers of cases are needed to clarify the precise association of renin-angiotensin system with the etiopathogenesis of pseudoexfoliation syndrome.

Assuntos

Angiotensina II/análise , Síndrome de Exfoliação/etiologia , Sistema Renina-Angiotensina , Renina/análise , Idoso , Idoso de 80 Anos ou mais , Humor Aquoso/metabolismo , Catarata/sangue , Extração de Catarata , Síndrome de Exfoliação/sangue , Síndrome de Exfoliação/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Prospectivos

RESUMO

OBJECTIVES: The present study aimed to investigate cardiovascular autonomic modulation and angiotensin II (Ang II) activity in diabetic mice that were genetically engineered to harbor two or three copies of the angiotensin-converting enzyme gene. METHODS: Diabetic and non-diabetic mice harboring 2 or 3 copies of the angiotensin-converting enzyme gene were used in the present study. Animals were divided into 4 groups: diabetic groups with two and three copies of the angiotensin-converting enzyme gene (2CD and 3CD) and the respective age-matched non-diabetic groups (2C and 3C). Hemodynamic, cardiovascular, and autonomic parameters as well as renal Ang II expression were evaluated. RESULTS: Heart rate was lower in diabetic animals than in non-diabetic animals. Autonomic modulation analysis indicated that the 3CD group showed increased sympathetic modulation and decreased vagal modulation of heart rate variability, eliciting increased cardiac sympathovagal balance, compared with all the other groups. Concurrent diabetes and either angiotensin-converting enzyme polymorphism resulted in a significant increase in Ang II expression in the renal cortex. CONCLUSION: Data indicates that a small increase in angiotensin-converting enzyme activity in diabetic animals leads to greater impairment of autonomic function, as demonstrated by increased sympathetic modulation and reduced cardiac vagal modulation along with increased renal expression of Ang II.

Assuntos

Angiotensina II/análise , Sistema Nervoso Autônomo/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Dosagem de Genes/fisiologia , Rim/enzimologia , Peptidil Dipeptidase A/genética , Angiotensina II/metabolismo , Animais , Glicemia/análise , Frequência Cardíaca/fisiologia , Imuno-Histoquímica , Masculino , Camundongos , Reação em Cadeia da Polimerase , Distribuição Aleatória , Nervo Vago/fisiopatologia

RESUMO

OBJECTIVES: The present study aimed to investigate cardiovascular autonomic modulation and angiotensin II (Ang II) activity in diabetic mice that were genetically engineered to harbor two or three copies of the angiotensin-converting enzyme gene. METHODS: Diabetic and non-diabetic mice harboring 2 or 3 copies of the angiotensin-converting enzyme gene were used in the present study. Animals were divided into 4 groups: diabetic groups with two and three copies of the angiotensin-converting enzyme gene (2CD and 3CD) and the respective age-matched non-diabetic groups (2C and 3C). Hemodynamic, cardiovascular, and autonomic parameters as well as renal Ang II expression were evaluated. RESULTS: Heart rate was lower in diabetic animals than in non-diabetic animals. Autonomic modulation analysis indicated that the 3CD group showed increased sympathetic modulation and decreased vagal modulation of heart rate variability, eliciting increased cardiac sympathovagal balance, compared with all the other groups. Concurrent diabetes and either angiotensin-converting enzyme polymorphism resulted in a significant increase in Ang II expression in the renal cortex. CONCLUSION: Data indicates that a small increase in angiotensin-converting enzyme activity in diabetic animals leads to greater impairment of autonomic function, as demonstrated by increased sympathetic modulation and reduced cardiac vagal modulation along with increased renal expression of Ang II.

Assuntos

Animais , Masculino , Camundongos , Sistema Nervoso Autônomo/fisiopatologia , Angiotensina II/análise , Sistema Cardiovascular/fisiopatologia , Peptidil Dipeptidase A/genética , Dosagem de Genes/fisiologia , Diabetes Mellitus Experimental/fisiopatologia , Rim/enzimologia , Nervo Vago/fisiopatologia , Glicemia/análise , Angiotensina II/metabolismo , Imuno-Histoquímica , Distribuição Aleatória , Reação em Cadeia da Polimerase , Frequência Cardíaca/fisiologia

RESUMO

Local renin angiotensin (RAS) system has been described in the ovary, which has been implicated invarious reproductive functions. To evaluate the ovarian RAS in, 13 goats were randomly divided into two groups:Enalapril (n = 7) and control (n = 6). Then, they received superovulation protocol. Enalapril further groupreceived subcutaneously (2mg/kg) enalapril maleate (0.4 mg/kg/day). Blood samples were collected on days 3, 6, 9and 11, and follicular fluid samples from pre-ovulatory ovarian follicles after exposure by celiotomy on D11. AngII in serum and follicular fluid were evaluated on days 9 and 12, Ang-(1-7) on day 12 by HPLC and RIA. E2 andP4 concentrations in serum were determined by ELISA. Ang-(1-7) concentrations in plasma was greater on day9 (P < 0.05), important period for the recruitment and follicular selection. This may indicate that these peptidescan an important function in follicular development and oocyte maturation in superovulated goats.

Assuntos

Animais , Angiotensina II/análise , Cabras/embriologia , Cabras/fisiologia , Inibidores da Enzima Conversora de Angiotensina/análise , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Peptídeos , Superovulação

RESUMO

There is increasing evidence the participation of ovarian renin-angiotensin system in importantreproductive processes. This study aimed to investigate the presence and location of Ang II, Ang-(1-7) and ACE2in goat ovaries. Ten ovaries from goats killed in slaughterhouse were collected, washed in buffered PBS,perfused with protease inhibitor solution and processed for histology standard protocol. The search of peptideswas performed using the avidin–biotin–peroxidase method. A strong immunoreactivity for Ang II in theca cellsof antral follicles and corpora lutea was observed. Antral follicles (theca cells), corpora lutea and oocytecytoplasm in early antral follicles exhibited strong immunoreactivity for Ang-(1-7). There was strongimmunoreactivity for ACE2 in the cytoplasm of luteal cells and theca cells of antral follicles. For the first time,the presence and location of Ang II, Ang-(1-7) and ACE2 are reported in goat ovary, can regulate folliculardevelopment, oocyte maturation and corpus luteum development.

Assuntos

Feminino , Animais , Angiotensina II/análise , Angiotensina II/análogos & derivados , Angiotensinas/administração & dosagem , Angiotensinas/análise , Ovário/citologia , Ovário/química , Cabras/fisiologia

RESUMO

There is increasing evidence the participation of ovarian renin-angiotensin system in importantreproductive processes. This study aimed to investigate the presence and location of Ang II, Ang-(1-7) and ACE2in goat ovaries. Ten ovaries from goats killed in slaughterhouse were collected, washed in buffered PBS,perfused with protease inhibitor solution and processed for histology standard protocol. The search of peptideswas performed using the avidin–biotin–peroxidase method. A strong immunoreactivity for Ang II in theca cellsof antral follicles and corpora lutea was observed. Antral follicles (theca cells), corpora lutea and oocytecytoplasm in early antral follicles exhibited strong immunoreactivity for Ang-(1-7). There was strongimmunoreactivity for ACE2 in the cytoplasm of luteal cells and theca cells of antral follicles. For the first time,the presence and location of Ang II, Ang-(1-7) and ACE2 are reported in goat ovary, can regulate folliculardevelopment, oocyte maturation and corpus luteum development.(AU)

Assuntos

Animais , Feminino , Angiotensinas/administração & dosagem , Angiotensinas/análise , Angiotensina II/análogos & derivados , Angiotensina II/análise , Ovário/química , Ovário/citologia , Cabras/fisiologia

RESUMO

Local renin angiotensin (RAS) system has been described in the ovary, which has been implicated invarious reproductive functions. To evaluate the ovarian RAS in, 13 goats were randomly divided into two groups:Enalapril (n = 7) and control (n = 6). Then, they received superovulation protocol. Enalapril further groupreceived subcutaneously (2mg/kg) enalapril maleate (0.4 mg/kg/day). Blood samples were collected on days 3, 6, 9and 11, and follicular fluid samples from pre-ovulatory ovarian follicles after exposure by celiotomy on D11. AngII in serum and follicular fluid were evaluated on days 9 and 12, Ang-(1-7) on day 12 by HPLC and RIA. E2 andP4 concentrations in serum were determined by ELISA. Ang-(1-7) concentrations in plasma was greater on day9 (P < 0.05), important period for the recruitment and follicular selection. This may indicate that these peptidescan an important function in follicular development and oocyte maturation in superovulated goats.(AU)

Assuntos

Animais , Cabras/embriologia , Cabras/fisiologia , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/análise , Angiotensina II/análise , Superovulação , Peptídeos

RESUMO

O presente trabalho teve como objetivo avaliar e comparar a reatividade vascular de agentes vasoconstritores presentes nas soluções anestésicas locais (Adrenalina - vasoconstrição e vasodilatação; Felipressina - vasoconstrição), nas doses de 80, 160, 320, 640 e 1280ng (adrenalina) ou 0,25; 0,5; 1; 2 e 4 x10-3UI (felipressina), em leito arterial mesentérico deratos normotensos, diabéticos, hipertensos renais um-rim, um-clip (1R-1C) e hipertensos1R-1C-diabéticos. E correlacionar tal reatividadecom expressão de RNAm dos receptores 1A e 2- adrenérgicos, V1A para vasopressina e AT1A, AT1Be AT2 para angiotensina II visando verificar se a hipertensão arterial e o diabetes mellitus provocam alteração em modelo indutivo e isogênico. Ratos Wistar pesando 110-160g, foram anestesiados com mistura de quetamina e xilazina (50+10mg/ml/kg de peso), tiveram seu abdômen aberto e receberam um clip de prata com abertura 0,25mm na artéria renal esquerda, removendo-se cirurgicamente o rim direito (ratos 1R-1C). Após 14 dias, receberam injeção subcutânea de estreptozotocina (50 e 60mg/kg de peso) para indução do diabetes mellitus sendo a glicemia testada pela veia caudal previamente aos experimentos (diabéticos). Após 30-42 dias da implantação do clip, todos os grupos foram novamente anestesiados e implantou-se cânula de polietileno (PE-50) na artéria carótida esquerda para registro direto da pressão arterial. Após registro da pressão os animais tiveram a artéria principal mesentérica exposta e canulada. O leito arterial mesentérico foi então isolado e colocado em banho com solução nutritiva de Krebs a 37ºC. O cateter foi conectado ao sistema de registro computadorizado (PowerLab®) utilizando software específico (Chart 5Pro ®). Analisaram-se: a pressão máxima (vasoconstrição) e mínima (vasodilatação), o tempo necessário para atingir esse valor, duração total da resposta, integral e integral sobre a linha de base. Os dados foram submetidos à análise de variância de medidas repetidas (ANOVA), seguida do teste de Holm-Sidak (distribuição normal) ou de Mann-Whitney (nãoparamétrico), quando apropriado, nível de significância de 5%. Todas as respostas máximas de vasoconstrição apresentaram comportamento dose-dependente, contudo, para os quatro grupos estudados, a resposta vasoconstritora para adrenalina foi significativamente superior à felipressina (p<0,05). Diabetes e hipertensão reduziram a resposta vasoconstritora da adrenalina e da felipressina, valores de integral sobre a linha de base, respectivamente para grupo controle, diabético, hipertenso e hipertenso-diabético: 2462±465; 1511±236; 2542± 5456 e 3749±819mmHg.s (p<0,05) para adrenalina e 3749 ± 708; 746 ± 103; 1647 ± 422; 1359 ± 591 mmHg.s (p<0,05) para felipressina. Tanto o diabetes quanto a hipertensão, associadas ou não, aumentaram significativamente o tempo para atingir a pressão máxima de vasoconstrição e a duração (p<0,05). As artérias mesentéricas de ratos diabéticos, hipertensos e diabéticos-hipertensos apresentaram expressão significativamente aumentada dos receptores 1Aadrenérgico, AT1B e AT2 para angiotensina II (p<0,05), enquanto receptor AT1A estava com a expressão aumentada apenas nos grupos diabéticos. A expressão do receptor 1A-adrenérgico é discrepante com os achados funcionais, o que pode ser justificado pela fase crônica da doença em que a PCR foi realizada. É possível correlacionar os dados obtidos com a menor atividade vasoconstritora da felipressina observada clinicamente. A maior sensibilidade às moléculas vasoconstritoras pode explicar a maior tendência de pacientes diabéticos desenvolverem hipertensão. A partir dos dados obtidos pode-se concluir que a adrenalina é o vasoconstritor mais potente que a felipressina e ambas as moléculas tem seus efeitos reduzidos em pacientes hipertensos e diabéticos, o que reforça a indicação de se utilizar anestésicos locais associados a vasoconstritores nestas populações.(AU)

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The main goal of this study wasto evaluate and compare vasoconstrictor agents present in local anesthetic solutions (Epinephrine - vasoconstriction and vasodilation, Felypressin - vasoconstriction) vascular reactivity on mesenteric artery bed of normotensive, diabetic, renal hypertensive one-kidney-one-clip (1K1C) and hypertensive 1K1C diabetic rats. Dosagesstudied were 80, 160, 320, 640 and 1280ng (epinephrine) or 0,25; 0,5;1; 2 and 4 x 10-3UI (felypressin). Also, we aimed to correlate artery response with RNAm expression of 1A and 2-adrenoceptors, V1A vasopressin receptor and AT1A, AT1B e AT2 angiotensin receptors, in order to verify if arterial hypertension and diabetes can lead to alterations on a inductive and isogenic model. Wistar male rats weighing 110-160g were anaesthetized with a mixture of ketamine and xylazine (50+10mg/ml/kg), had their abdominal cavity opened and a silver clipwith 0.25-mm gap was implanted in the main left kidney artery, the right kidney was surgically removed (1K1C-rats). After 14 days, they received a subcutaneous injection of streptozotocin (50 and 60 mg/ml/kg) for inducing diabetes, whereas the glycemia was tested via the tail vein prior to surgery (diabetic rats). Around 30-42 after the clip was implanted, all the groups were anaesthetized again and a polyethylene (PE-50) cannula was implanted on the left carotid artery for direct arterial pressure register. After registering the pressure, the animals had their main mesenteric artery exposed and cannulated. The mesenteric artery bed was then isolated and transferred to a bath with Krebs nutritive solution at 37ºC. The catheter was connected to the computer register system (PowerLab®) using a specific software (Chart 5Pro ®). The following parameters were analyzed: maximum (vasoconstriction) and minimal pressure (vasodilating), the amount of time necessary to achieve this number, total duration of the reaction, integral and integral over baseline. The data was submitted to analysis of variance of repeated measures (ANOVA), followed by a Holm-Sidak (normal distribution) test or Mann Whitney (parametrics) test when suitable, with a significance level of 5%. All maximum vasoconstriction results presented dosage-dependant behavior, however, for the four groups tested, the vasoconstrictive result for epinephrine was significantly superior to felypressin (p<0,05). Diabetes and hypertension significantly reducedepinephrine and felypressin vasoconstrictor responses, integral above baseline, respectively, for control, diabetic, hypertensive and hypertensive-diabetic groups:2462±465; 1511±236; 2542± 5456 e 3749±819 mmHg.s (p<0.05, epinephrine) and 3749 ± 708; 746 ± 103; 1647 ± 422; 1359 ± 591 mmHg.s (p<0.05, felypressin). Both diabetes and hypertension, associated or not, significantly increased time necessary to achieve maximum vasoconstrictor response and its duration (p<0,05). Diabetic, hypertensive and hypertensive-diabetic mesenteric arteries presented 1A-adrenoceptor, AT1B and AT2 angiotensin II-receptor gene expression significantly increased when compared with control group (p<0,05), while AT1Areceptor presented this pattern only in diabetic groups.1A-adrenoceptor gene expression did not confirm functional data, probably due to chronic disease state in wich PCR was performed. A partir dos dados obtidos pode-se concluir que a adrenalina é o vasoconstritor mais potente que a felipressina e ambas as moléculas tem seus efeitos reduzidos em ratos hipertensos e diabéticos não tratados, o que reforça a indicação de se utilizar anestésicos locais associados a vasoconstritores nestas populações.Its possible to correlate our datawith reducedvasoconstrictor activity of felypressinin clinical use. Increased sensibility and receptor population for vasoconstrictor endogenous molecules could explain diabetic populations tendency to develop arterial hypertension. Our results suggest that epinephrine is more potent than felypressin and both vasoconstrictors presents reduced effects on diabetic and hypertensive patients, what reinforces vasoconstrictor associated with local anesthetic use in this population.(AU)

Assuntos

Animais , Masculino , Ratos , Anestésicos Locais/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Epinefrina/farmacologia , Felipressina/farmacologia , Hipertensão/fisiopatologia , Artérias Mesentéricas/efeitos dos fármacos , Vasoconstritores/farmacologia , Agonistas de Receptores Adrenérgicos beta 2/análise , Angiotensina II/análise , Ratos Wistar , Receptores Adrenérgicos alfa 1/análise , Fatores de Tempo , Vasoconstrição/efeitos dos fármacos , Vasopressinas/análise

RESUMO

O Sistema renina-angiotensina (SRA) tem sido relatado como um importante modulador de processos inflamatórios e imunológicos, incluindo a doença periodontal (DP). Estudos sugerem neste sistema um eixo alternativo (ECA-2 /ANG(1-7) /MAS) que atuaria como um contra-regulador de efeitos mediados pelo clássico eixo (ECA /ANGII /AT1). Sabe-se que bactérias periodontopatogênicas, como a Porphyromonas gingivalis (Pg), possuem componentes bioativos de membrana (ex. lipopolissacarídeos-LPS) capazes de induzir uma forte resposta imune no hospedeiro devido à liberação de citocinas nas células, entre elas Interleucina (IL)- 1ß. Neste contexto, fibroblastos são as células mais abundantes nos tecidos periodontais e possuem em sua superfície celular receptores necessários para o reconhecimento da invasão bacteriana, ativando cascatas intracelulares, que levam à produção de citocinas. O objetivo deste estudo foi verificar se os eixos ECA/ ANGII/ AT1 e ECA-2/ ANG(1-7)/ MAS contribuem para a produção e/ ou regulação de citocinas inflamatórias (CI) por fibroblastos de gengiva humana (HGF) e ligamento periodontal humano (HPLF) estimulados por IL-1ß. Após o pré-tratamento com Losartan e Ang (1-7) ou silenciamento mediado por RNA de interferência (RNAi) de AT1, HGF e HPLF foram estimulados por IL-1ß por 3 horas (RNAm) ou 24 horas (proteína). Expressão de RNAm para AT1, MAS, ECA, ECA-2, IL-1ß, TNF-α, IL-6, IL-8, IL-10, TGF-ß, CXCL12, RANK-L e OPG foram avaliados por RT-qPCR e das proteínas IL-6, IL-8, ECA e ECA-2 por ELISA. Foi realizado também Western Blot para detecção de AT1 e ECA nos extratos celulares e dosagem de nitrito no sobrenadante das culturas. Ambos os subtipos de fibroblastos mostraram aumento da expressão de RNAm para AT1, IL-1ß, IL-6, IL-8, TNF-α e OPG, quando estimulados por IL-1ß. No entanto, apenas em HPLF foi observado aumento para MAS, ECA e TGF-ß. Losartan e Ang (1-7) não modularam o transcrito, a secreção de CI e nem a produção de nitrito no sobrenadante das culturas, tanto em HGF como em HPLF. O silenciamento do receptor AT1 reduziu a secreção de IL-6 e IL-8 induzida por IL-1ß em cultura de HGF e HPLF e aumentou a expressão gênica de OPG somente em HGF. Estes resultados sugerem que o silenciamento de AT1, mas não o bloqueio farmacológico deste receptor pelo antagonista Losartan, em HGF e HPLF, pode controlar a produção de IL-6 e IL-8, que por sua vez contribuem para a patogênese periodontal.(AU)

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The renin-angiotensin system (RAS) has been reported as an important modulator of inflammatory and immune responses, including periodontal disease (PD). Studies suggest an alternative axis as part of this system (ACE-2 / ANG (1-7) / MAS) that would act as counter-regulatory to the classical axis (ECA / ANGII / AT1). It is known that periodontal bacteria such as Porphyromonas gingivalis (Pg) have bioactive components in their membrane (such as lipopolysaccharide-LPS) capable of inducing a strong immune response in the host due to the release of cytokines in cells, including interleukin (IL) - 1ß. In this regard, fibroblasts are the most abundant cells in periodontal tissues and receptors needed for the recognition of bacterial invasion by activating intracellular cascades that lead to cytokine production. The aim of this study was to determine whether the axes ACE / ANGII / AT1 and ACE-2 / ANG (1-7) / MAS contribute to the production and / or regulation of inflammatory cytokines (IC) by fibroblasts of human gingiva (HGF) and human periodontal ligament (HPLF) stimulated IL-1ß. After pre-treatment with Losartan, Ang (1-7) or silencing mediated by RNA interference (RNAi) of AT1, HGF and HPLF were stimulated by IL-1ß for 3 hours (RNAm) or 24 hours (protein). Expression mRNA for AT1, MAS, ACE, ACE-2, IL-1ß, TNF-α, IL-6, IL-8, IL-10, TGF-ß, CXCL12, RANK-L and OPG was assessed by RT- qPCR and proteins IL-6, IL-8, ACE and ACE-2 by ELISA. Western Blot for the detection of AT1 and ECA and dosage of nitrite was also performed. Experiments stimulated by IL-1ß showed a positive control for gene expression AT1, IL-1ß, IL-6, IL-8, TNF-α and OPG in HGF and HPLF and MAS, ACE and TGF-ß only HPLF. Losartan and Ang (1-7) did not modulate the transcription and secretion of IC and no nitrite production in the culture supernatant of HGF and HPLF. The silencing AT1 reduced IL-6 secretion and IL-8 induced by IL- ß in cultured HGF and HPLF and increased OPG gene expression only HGF. These results suggest that silencing AT1, but not pharmacological blockade of this receptor by Losartan in HPLF and HGF, can control the production of IL-6 and IL-8, which in turn contribute to the pathogenesis of periodontal disease.(AU)

Assuntos

Humanos , Quimiocinas/metabolismo , Citocinas/metabolismo , Fibroblastos/fisiologia , Interleucina-1beta/fisiologia , Sistema Renina-Angiotensina/fisiologia , Análise de Variância , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Angiotensina II/análise , Angiotensina II/fisiologia , Angiotensina I/análise , Angiotensina I/fisiologia , Western Blotting , Células Cultivadas , Quimiocinas/análise , Citocinas/análise , Gengiva/citologia , Losartan/farmacologia , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/fisiologia , Peptidil Dipeptidase A/análise , Peptidil Dipeptidase A/fisiologia , Ligamento Periodontal/citologia , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/fisiologia , Receptor Tipo 1 de Angiotensina/análise , Receptor Tipo 1 de Angiotensina/fisiologia

RESUMO

The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression were found between healthy and diseased gingiva. However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts. When compared to healthy tissue, ACE activity was increased in human gingiva from volunteers with gingivitis. Human-gingiva homogenates generated Ang II, Ang 1-9 and Ang 1-7 when incubated with precursors. In gingiva homogenates, Ang II formation from Ang I was nearly abolished only when captopril and chymostatin were combined. Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin. In rat gingiva, RAS components were also found; their expression was not different between healthy and experimentally induced periodontitis (EP) groups. However, renin inhibition (aliskiren) and an AT1R antagonist (losartan) significantly blocked EP-alveolar-bone loss in rats. Collectively, these data are consistent with the hypothesis that a local RAS system is not only present but is also functional in both human and rat periodontal tissue. Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

Assuntos

Periodontite/imunologia , Periodontite/patologia , Periodonto/imunologia , Periodonto/patologia , Sistema Renina-Angiotensina , Adulto , Sequência de Aminoácidos , Angiotensina I/análise , Angiotensina I/imunologia , Angiotensina II/análise , Angiotensina II/imunologia , Animais , Células Cultivadas , Feminino , Gengiva/citologia , Gengiva/imunologia , Gengiva/patologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/imunologia , Ratos Wistar , Receptores de Angiotensina/análise , Receptores de Angiotensina/imunologia , Renina/imunologia , Adulto Jovem

RESUMO

We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT2R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT2R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca2+-free medium or the subsequent tonic constrictions induced by the addition of Ca2+ in the absence of agonists. Thus, the contractions induced by Ca2+ release from intracellular stores and Ca2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca2+. Neither levels of angiotensins nor of AT2R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca2+ entry.

Assuntos

Animais , Masculino , Aorta Torácica/fisiopatologia , Coartação Aórtica/fisiopatologia , Cálcio/metabolismo , Endotélio Vascular/fisiologia , Músculo Liso Vascular/fisiopatologia , Proteína Quinase C/antagonistas & inibidores , Vasoconstrição/fisiologia , Angiotensina I/análise , Angiotensina II/análise , Aorta Torácica/lesões , Aorta Torácica/cirurgia , Western Blotting , Pressão Sanguínea/fisiologia , Cromatografia Líquida de Alta Pressão , Endotélio Vascular/lesões , Músculo Liso Vascular/metabolismo , Fármacos Neuromusculares Despolarizantes/farmacologia , Fenilefrina/farmacologia , Potássio/farmacologia , Proteína Quinase C/metabolismo , Radioimunoensaio , Ratos Wistar , /metabolismo , Vasoconstrição/efeitos dos fármacos

RESUMO

We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT2R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT2R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca2+-free medium or the subsequent tonic constrictions induced by the addition of Ca2+ in the absence of agonists. Thus, the contractions induced by Ca2+ release from intracellular stores and Ca2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca2+. Neither levels of angiotensins nor of AT2R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca2+ entry.

Assuntos

Aorta Torácica/fisiopatologia , Coartação Aórtica/fisiopatologia , Cálcio/metabolismo , Endotélio Vascular/fisiologia , Músculo Liso Vascular/fisiopatologia , Proteína Quinase C/antagonistas & inibidores , Vasoconstrição/fisiologia , Angiotensina I/análise , Angiotensina II/análise , Animais , Aorta Torácica/lesões , Aorta Torácica/cirurgia , Pressão Sanguínea/fisiologia , Western Blotting , Cromatografia Líquida de Alta Pressão , Endotélio Vascular/lesões , Masculino , Músculo Liso Vascular/metabolismo , Fármacos Neuromusculares Despolarizantes/farmacologia , Fenilefrina/farmacologia , Potássio/farmacologia , Proteína Quinase C/metabolismo , Radioimunoensaio , Ratos Wistar , Receptor Tipo 2 de Angiotensina/metabolismo , Vasoconstrição/efeitos dos fármacos

RESUMO

PURPOSE: Evaluation of colonic healing in spontaneously hypertensive rats. METHODS: Fifty male, young and inbred rats were used. Twenty-five Wistar Kyoto rats (WKY) as control and twenty-five spontaneously hypertensive rats (SHR) as an experimental group. Colotomy and bowel suture at 2.5 cm from the peritoneal reflection were performed. All animals were allocated randomly into sub-groups for review at the third, seventh and fourteenth days after surgery. We evaluated the concentration of angiotensin II, the burst pressure, epithelialization, the organization of the tunics of the bowel wall, inflammatory response and collagen deposition. RESULTS: The burst pressure, epithelialization, organization of the tunics and collagen deposition was not significant between groups. The inflammatory reaction was more intense in the control group on the third postoperative day (p=0.023) as the experimental group on the remaining time. CONCLUSION: Systemic arterial hypertension in rats did not influence significantly the healing process of colonic anastomoses.

Assuntos

Colo/cirurgia , Hipertensão/fisiopatologia , Cicatrização/fisiologia , Anastomose Cirúrgica , Angiotensina II/análise , Animais , Pressão Sanguínea/fisiologia , Colágeno/metabolismo , Colo/patologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Masculino , Período Pós-Operatório , Distribuição Aleatória , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Deiscência da Ferida Operatória/fisiopatologia , Fatores de Tempo

RESUMO

PURPOSE: Evaluation of colonic healing in spontaneously hypertensive rats. METHODS: Fifty male, young and inbred rats were used. Twenty-five Wistar Kyoto rats (WKY) as control and twenty-five spontaneously hypertensive rats (SHR) as an experimental group. Colotomy and bowel suture at 2.5 cm from the peritoneal reflection were performed. All animals were allocated randomly into sub-groups for review at the third, seventh and fourteenth days after surgery. We evaluated the concentration of angiotensin II, the burst pressure, epithelialization, the organization of the tunics of the bowel wall, inflammatory response and collagen deposition. RESULTS: The burst pressure, epithelialization, organization of the tunics and collagen deposition was not significant between groups. The inflammatory reaction was more intense in the control group on the third postoperative day (p=0.023) as the experimental group on the remaining time. CONCLUSION: Systemic arterial hypertension in rats did not influence significantly the healing process of colonic anastomoses.

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OBJETIVO: Avaliar a cicatrização colônica em ratos espontaneamente hipertensos. MÉTODOS: Cinquenta ratos machos, jovens e isogênicos. Vinte e cinco ratos da linhagem Wistar Kyoto (WKY) como controle e vinte e cinco ratos espontaneamente hipertensos (SHR) como grupo experimento. Realizou-se colotomia e colorrafia a 2,5 cm da reflexão peritoneal. Alocaram-se os animais aleatoriamente em sub-grupos para avaliação no terceiro, sétimo e décimo quarto dias de pós-operatório. Foram avaliados a concentração de angiotensina II, a resistência da anastomose à insuflação, a epitelização, a organização das túnicas da parede intestinal, a reação inflamatória e a deposição de colágeno. RESULTADOS: A avaliação da resistência da anastomose, epitelização, organização das túnicas e deposição de colágeno não foi significativa entre os grupos. A reação inflamatória foi mais intensa no grupo controle na avaliação do terceiro dia de pós-operatório (p=0,023) igualando-se ao grupo experimento nos demais tempos. CONCLUSÃO: A hipertensão arterial sistêmica, em ratos, não influenciou de forma significante no processo cicatricial de anastomoses do cólon.

Assuntos

Animais , Masculino , Ratos , Colo/cirurgia , Hipertensão/fisiopatologia , Cicatrização/fisiologia , Anastomose Cirúrgica , Angiotensina II/análise , Pressão Sanguínea/fisiologia , Colágeno/metabolismo , Colo/patologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Período Pós-Operatório , Distribuição Aleatória , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Deiscência da Ferida Operatória/fisiopatologia , Fatores de Tempo

RESUMO

High salt intake is a known cardiovascular risk factor and is associated with cardiac alterations. To better understand this effect, male Wistar rats were fed a normal (NSD: 1.3% NaCl), high 4 (HSD4: 4%), or high 8 (HSD8: 8%) salt diet from weaning until 18 wk of age. The HSD8 group was subdivided into HSD8, HSD8+HZ (15 mg . kg(-1) . d(-1) hydralazine in the drinking water), and HSD8+LOS (20 mg . kg(-1) . d(-1) losartan in the drinking water) groups. The cardiomyocyte diameter was greater in the HSD4 and HSD8 groups than in the HSD8+LOS and NSD groups. Interstitial fibrosis was greater in the HSD4 and HSD8 groups than in the HSD8+HZ and NSD groups. Hydralazine prevented high blood pressure (BP) and fibrosis, but not cardiomyocyte hypertrophy. Losartan prevented high BP and cardiomyocyte hypertrophy, but not fibrosis. Angiotensin II type 1 receptor (AT(1)) protein expression in both ventricles was greater in the HSD8 group than in the NSD group. Losartan, but not hydralazine, prevented this effect. Compared with the NSD group, the binding of an AT(1) conformation-specific antibody that recognizes the activated form of the receptor was lower in both ventricles in all other groups. Losartan further lowered the binding of the anti-AT(1) antibody in both ventricles compared with all other experimental groups. Angiotensin II was greater in both ventricles in all groups compared with the NSD group. Myocardial structural alterations in response to HSD are independent of the effect on BP. Salt-induced cardiomyocyte hypertrophy and interstitial fibrosis possibly are due to different mechanisms. Evidence from the present study suggests that salt-induced AT(1) receptor internalization is probably due to angiotensin II binding.

Assuntos

Pressão Sanguínea/fisiologia , Cardiomegalia/induzido quimicamente , Cardiomegalia/fisiopatologia , Miocárdio/patologia , Cloreto de Sódio na Dieta/administração & dosagem , Aldosterona/sangue , Angiotensina II/análise , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Animais , Anti-Hipertensivos/administração & dosagem , Cardiomegalia/patologia , Colágeno Tipo I/análise , Colágeno Tipo III/análise , Modelos Animais de Doenças , Ingestão de Líquidos , Ingestão de Alimentos , Ecocardiografia , Fibrose , Expressão Gênica , Ventrículos do Coração/química , Ventrículos do Coração/patologia , Hidralazina/administração & dosagem , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Losartan/administração & dosagem , Masculino , Potássio/sangue , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/análise , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/fisiologia , Receptor Tipo 2 de Angiotensina/análise , Renina/sangue , Sistema Renina-Angiotensina/genética , Sistema Renina-Angiotensina/fisiologia , Sódio/sangue , Sódio/urina , Fator de Crescimento Transformador beta/análise , Urina

RESUMO

Background: Oocytes are arrested in the first meiotic prophase during follicular development until near ovulation. In vitro, oocytes resume meiosis spontaneously, germinal vesicle breakdown (GVBD) occurs and oocytes progress to the MII stage when they are removed from their follicles and cultured under suitable conditions. On the other hand, meiotic maturation of bovine oocytes occurs within the follicle, raising the question regarding possible involvement of positive signal(s) to induce meiotic resumption in vivo. Meiotic resumption is dependent on the preovulatory surge of LH, but the bovine cumulus­oocyte complexes (COCs) do not have LH receptors, so the signal must occur through theca and mural granulosa cells. The LH surge stimulated the ovarian renin-angiotensin system (RAS), including an increase in the renin activity and angiotensin II (AngII) concentration in bovine follicular fluid. Also, the interactions among LH, AngII increased follicular production of prostaglandins (PGs) and modulated steroidogenesis in the bovine preovulatory follicle. AngII has also been associated with follicular growth and ovulation in cows. Furthermore, AngII stimulated the resumption of meiosis in co-culture systems of cumulus enclosed bovine oocytes and follicular cells. Review: The presence of prorenin, renin, angiotensinogen, angiotensin-converting enzyme, angiotensin II (Ang II) and Ang II receptors in the ovary is suggestive of a functional ovarian RAS. In the last few years, our research group has focused on studying the contribution of RAS in antral follicle development, ovulation and oocyte maturation. A new concept of mechanism and factors involved in oocyte meiotic resumption has been established using cattle as a model. Transvaginal ultrasound has been used for intrafollicular injection to investigate factors that play a part in the resumption of meiosis. With this in vivo and an in vitro model, culturing oocytes in the presence of theca and granulosa cells, we have demonstrated that AngII via the AT2 receptor subtype plays a pivotal role in the antral follicle development, early mechanism of ovulation and oocyte meiotic resumption in cattle. When bovine cumulus-oocyte complexes (COCs) are cultured with follicular hemisections, oocyte maturation is inhibited; however, follicular cells or conditioned medium were unable to inhibit nuclear maturation in the presence of AngII. In vivo, intrafollicular injection of saralasin (a competitive AngII antagonist) completely inhibited the oocyte meiotic resumption in follicles (larger than 12 mm) challenged with an GnRH agonist. Moreover, oocytes co-cultured with follicular hemisections progressed nuclear maturation when prostaglandin E2 (PGE2), PGF2a, progesterone, oxitocin or AngII was present in the coculture system and indomethacin inhibited AngII-induced meiotic resumption. Conclusion: our results provide strong evidence that AngII mediates the oocyte meiotic resumption induced by an LH surge in cattle and that this event is dependent on progesterone, oxytocin and prostaglandin.

Assuntos

Animais , Bovinos , Progesterona/análise , Angiotensina II/análise , Ocitocina/análise , Prostaglandinas/análise , Meiose/fisiologia , Oócitos