RESUMO
OBJECTIVE: To describe and to characterize the relaxing effect of an extract of the bark of Combretum leprosum on isolated arterial rings from different animals. METHODS: Rings (3 to 4mm) from rabbit, rat, or porcine arteries rings were suspended in an organ bath (Krebs, 37°C, 95%O2/5%CO2) to record isometric contractions. After the stabilization period (2 to 3 hours) contractions were induced by the addition of phenylephrine (0.1 to 0.3µM) or U46619 (10 to 100nM), and Combretum leprosum extract was added on the plateau of the contractions. Experiments were performed to determine the potency, duration, reversibility, and to get insights on the potential mechanism involved in extract-induced relaxations. RESULTS: In all rings tested, Combretumleprosum extract (1.5µg/mL) was able to cause relaxations, which were strictly endothelium-dependent. In rabbit or rat thoracic aorta rings, the relaxations were reversed by vitamin B12a or L-NG-nitroarginine. In porcine right coronary arteries and rabbit abdominal aorta, extract caused both L-NG-nitroarginine-sensitive and L-NG-nitroarginine-resistant relaxations. In rabbit thoracic aorta, the extract was relatively potent (EC50=0.20µg/mL) and caused relaxations; intriguingly the endothelium continued to produce relaxing factors for a long period after removing the extract. The magnitude of extract-induced relaxations was significantly reduced in the absence of extracellular Ca2+; in addition, the TRPs channels blocker ruthenium red (10µM) was able to revert extract-induced relaxations. Phytochemical analyses indicated that the extract was rich in polyphenol-like reacting substances. CONCLUSIONS: Combretum leprosum extract contains bioactive compounds capable of promoting Ca2+-dependent stimulation of endothelial cells which results in a prolonged production of relaxing factors.
Assuntos
Combretum/química , Fatores Relaxantes Dependentes do Endotélio/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Óxido Nítrico/farmacologia , Acetilcolina/farmacologia , Animais , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/fisiologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Artéria Carótida Primitiva/efeitos dos fármacos , Artéria Carótida Primitiva/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Feminino , Cobaias , Masculino , Artéria Mesentérica Superior/efeitos dos fármacos , Artéria Mesentérica Superior/fisiologia , Camundongos , Relaxamento Muscular/fisiologia , Casca de Planta/química , Coelhos , Ratos Wistar , Suínos , Fatores de TempoRESUMO
Objective To describe and to characterize the relaxing effect of an extract of the bark of Combretum leprosum on isolated arterial rings from different animals.Methods Rings (3 to 4mm) from rabbit, rat, or porcine arteries rings were suspended in an organ bath (Krebs, 37°C, 95%O2/5%CO2) to record isometric contractions. After the stabilization period (2 to 3 hours) contractions were induced by the addition of phenylephrine (0.1 to 0.3µM) or U46619 (10 to 100nM), and Combretum leprosum extract was added on the plateau of the contractions. Experiments were performed to determine the potency, duration, reversibility, and to get insights on the potential mechanism involved in extract-induced relaxations.Results In all rings tested, Combretumleprosum extract (1.5μg/mL) was able to cause relaxations, which were strictly endothelium-dependent. In rabbit or rat thoracic aorta rings, the relaxations were reversed by vitamin B12a or L-NG-nitroarginine. In porcine right coronary arteries and rabbit abdominal aorta, extract caused both L-NG-nitroarginine-sensitive and L-NG-nitroarginine-resistant relaxations. In rabbit thoracic aorta, the extract was relatively potent (EC50=0.20µg/mL) and caused relaxations; intriguingly the endothelium continued to produce relaxing factors for a long period after removing the extract. The magnitude of extract-induced relaxations was significantly reduced in the absence of extracellular Ca2+; in addition, the TRPs channels blocker ruthenium red (10µM) was able to revert extract-induced relaxations. Phytochemical analyses indicated that the extract was rich in polyphenol-like reacting substances.ConclusionsCombretum leprosum extract contains bioactive compounds capable of promoting Ca2+-dependent stimulation of endothelial cells which results in a prolonged production of relaxing factors.
Objetivo Descrever e caracterizar os relaxamentos induzidos por um extrato das cascas de Combretum leprosum em anéis de artérias de diferentes espécies de animais.Métodos Anéis (3 a 4mm) de artérias de coelho, rato e porco foram montados em cubas para órgão isolado (Krebs, 37°C, 95%O2/5%CO2) para registro das contrações isométricas. Após um período de estabilização (2 a 3 horas), as contrações foram induzidas com fenilefrina (0,1 a 0,3µM) ou U46619 (10 a 100nM); no platô dessas contrações, adicionamos o extrato Combretum leprosum. Diferentes protocolos foram realizados para determinar potência, duração, reversibilidade e mecanismo dos relaxamentos induzidos pelo extrato.Resultados Em todas as preparações testadas, o extrato de Combretum leprosum (1,5µg/mL) provocou relaxamentos dependentes de endotélio. Em aorta torácica de coelho ou rato, os relaxamentos foram revertidos pela vitamina B12a ou L-NG-nitro-arginina. Em anéis de aorta abdominal de coelho e de artérias coronárias de porco, o extrato causou relaxamentos sensíveis e resistentes à L-NG-nitro-arginina. Em aorta torácica de coelho, o extrato foi relativamente muito potente (EC50=0,20μg/mL) e quando causou relaxamentos; intrigantemente o endotélio continuou a produzir fatores relaxantes por um longo período após remoção do extrato. A magnitude dos relaxamentos induzidos pelo extrato foi significativamente reduzida em ausência Ca2+ extracelular; ademais, o vermelho de rutênio (10μM), um bloqueador de canais TRPs, foi capaz de reverter os relaxamentos induzidos pelo extrato. Análises preliminares indicaram que o extrato continha compostos com reatividade química semelhante à polifenóis.Conclusão O extrato de Combretum leprosum contem compostos bioativos capazes de promover estimulação dependente de Ca2+ das células endoteliais a qual resulta numa produção prolongada de fatores relaxantes.
Assuntos
Animais , Feminino , Cobaias , Masculino , Camundongos , Coelhos , Combretum/química , Fatores Relaxantes Dependentes do Endotélio/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Óxido Nítrico/farmacologia , Acetilcolina/farmacologia , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/fisiologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Artéria Carótida Primitiva/efeitos dos fármacos , Artéria Carótida Primitiva/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Artéria Mesentérica Superior/efeitos dos fármacos , Artéria Mesentérica Superior/fisiologia , Relaxamento Muscular/fisiologia , Casca de Planta/química , Ratos Wistar , Suínos , Fatores de TempoRESUMO
We examined superior mesenteric artery blood flow velocity in response to feeding in infants randomized to trophic feeds (n = 16) or nil per os (n = 18) during previous treatment for patent ductus arteriosus. Blood flow velocity increased earlier in the fed infants, but was similar in the 2 groups at 30 minutes after feeding.
Assuntos
Velocidade do Fluxo Sanguíneo , Permeabilidade do Canal Arterial/tratamento farmacológico , Artéria Mesentérica Superior/diagnóstico por imagem , Inibidores de Ciclo-Oxigenase/uso terapêutico , Nutrição Enteral , Feminino , Humanos , Ibuprofeno/uso terapêutico , Indometacina/uso terapêutico , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Masculino , Artéria Mesentérica Superior/fisiologia , Ultrassonografia DopplerRESUMO
BACKGROUND: Arterial hypertension is a multifactorial chronic condition caused by either congenital or acquired factors. OBJECTIVE: To evaluate the effects of Resistance Training (RT) on arterial pressure, and on vascular reactivity and morphology, of L-NAME-treated hypertensive rats. METHODS: Male Wistar rats (200 - 250 g) were allocated into Sedentary Normotensive (SN), Sedentary Hypertensive (SH) and Trained Hypertensive (TH) groups. Hypertension was induced by adding L-NAME (40 mg/Kg) to the drinking water for four weeks. Arterial pressure was evaluated before and after RT. RT was performed using 50% of 1RM, 3 sets of 10 repetitions, 3 times per week for four weeks. Vascular reactivity was measured in rat mesenteric artery rings by concentration-response curves to sodium nitroprusside (SNP); phenylephrine (PHE) was also used for histological and stereological analysis. RESULTS: Resistance training inhibited the increase in mean and diastolic arterial pressures. Significant reduction was observed in Rmax (maximal response) and pD2 (potency) of PHE between SH and TH groups. Arteries demonstrated normal intima, media and adventitia layers in all groups. Stereological analysis demonstrated no significant difference in luminal, tunica media, and total areas of arteries in the SH and TH groups when compared to the SN group. Wall-to-lumen ratio of SH arteries was significantly different compared to SN arteries (p<0.05) but there was no difference when compared to TH arteries. CONCLUSIONS: RT was able to prevent an increase in blood pressure under the conditions in this study. This appears to involve a vasoconstrictor regulation mechanism and maintenance of luminal diameter in L-NAME induced hypertensive rats.
Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/metabolismo , Condicionamento Físico Animal/métodos , Treinamento Resistido , Vasoconstrição/fisiologia , Análise de Variância , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Hipertensão/induzido quimicamente , Hipertensão/patologia , Masculino , Artéria Mesentérica Superior/fisiologia , NG-Nitroarginina Metil Éster , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Vasoconstritores/farmacologia , Vasodilatadores/farmacologiaRESUMO
FUNDAMENTO: A hipertensão arterial é uma síndrome multifatorial, crônica, causada tanto por fatores congênitos ou adquiridos. OBJETIVO: Avaliar os efeitos do treinamento físico resistido (TR) sobre pressão arterial, reatividade e morfologia vascular de ratos hipertensos induzidos por L-NAME. MÉTODOS: Ratos Wistar machos (200-250 g) foram divididos em 3 grupos: normotenso sedentário (NS), hipertenso sedentário (HS) e hipertenso treinado (HT). A hipertensão foi induzida pela administração de L-NAME (40 mg/kg) na água de beber por 4 semanas. A pressão arterial foi avaliada antes e após o TR. O TR foi realizado utilizando 50% de 1RM, em 3 séries de 10 repetições, 3 vezes por semana, durante quatro semanas. A reatividade vascular foi mensurada em artéria mesentérica superior por curvas concentração resposta ao nitroprussiato de sódio (NPS) e fenilefrina (FEN). Além disso, foram realizadas análises histológicas e estereológicas. RESULTADOS: O TR inibiu o aumento das pressões arteriais média e diastólica. Foi observada uma redução significativa na resposta máxima e na potência da FEN entre os grupos HS e HT. A análise histológica evidenciou aspecto normal para as túnicas íntima, média e adventícia em todos os grupos. Não houve diferença significativa nas áreas do lúmen, da túnica média e total das artérias dos grupos HS e HT em relação ao NS. A razão parede/lúmen arterial do grupo HS apresentou diferença significativa em relação ao NS (p < 0,05), mas esta não foi diferente do HT. CONCLUSÕES: O TR foi capaz de prevenir a elevação da pressão arterial sob as condições deste estudo. Este controle parece envolver a regulação de mecanismo vasoconstritor e a manutenção do diâmetro luminal de ratos hipertensos induzidos por L-NAME.
BACKGROUND: Arterial hypertension is a multifactorial chronic condition caused by either congenital or acquired factors. OBJECTIVE: To evaluate the effects of Resistance Training (RT) on arterial pressure, and on vascular reactivity and morphology, of L-NAME-treated hypertensive rats. METHODS: Male Wistar rats (200 - 250 g) were allocated into Sedentary Normotensive (SN), Sedentary Hypertensive (SH) and Trained Hypertensive (TH) groups. Hypertension was induced by adding L-NAME (40 mg/Kg) to the drinking water for four weeks. Arterial pressure was evaluated before and after RT. RT was performed using 50% of 1RM, 3 sets of 10 repetitions, 3 times per week for four weeks. Vascular reactivity was measured in rat mesenteric artery rings by concentration-response curves to sodium nitroprusside (SNP); phenylephrine (PHE) was also used for histological and stereological analysis. RESULTS: Resistance training inhibited the increase in mean and diastolic arterial pressures. Significant reduction was observed in Rmax (maximal response) and pD2 (potency) of PHE between SH and TH groups. Arteries demonstrated normal intima, media and adventitia layers in all groups. Stereological analysis demonstrated no significant difference in luminal, tunica media, and total areas of arteries in the SH and TH groups when compared to the SN group. Wall-to-lumen ratio of SH arteries was significantly different compared to SN arteries (p<0.05) but there was no difference when compared to TH arteries. CONCLUSIONS: RT was able to prevent an increase in blood pressure under the conditions in this study. This appears to involve a vasoconstrictor regulation mechanism and maintenance of luminal diameter in L-NAME induced hypertensive rats.
Assuntos
Animais , Masculino , Ratos , Pressão Sanguínea/fisiologia , Hipertensão/metabolismo , Condicionamento Físico Animal/métodos , Treinamento Resistido , Vasoconstrição/fisiologia , Análise de Variância , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Hipertensão/induzido quimicamente , Hipertensão/patologia , Artéria Mesentérica Superior/fisiologia , NG-Nitroarginina Metil Éster , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Distribuição Aleatória , Ratos Wistar , Vasoconstritores/farmacologia , Vasodilatadores/farmacologiaRESUMO
The present study investigated the mechanisms underlying the vasorelaxant effects of the essential oil of Aniba canelilla (EOAC) and its main constituent 1-nitro-2-phenylethane (NP) in isolated superior mesenteric artery from spontaneously hypertensive rats (SHRs). At 0.1-1000 µg/mL, EOAC and NP relaxed SMA preparations pre-contracted with 75 mMKCl with IC(50) (geometric mean [95% confidence interval]) values of 294.19 [158.20-94.64] and 501.27 [378.60-624.00] µg/mL, respectively); or with phenylephrine (PHE) (IC(50)s=11.07 [6.40-15.68] and 7.91 [4.08-11.74) µg/mL, respectively). All these effects were reversible and remained unaltered by vascular endothelium removal. In preparations maintained under Ca(2+)-free conditions, EOAC and NP (both at 600 µg/mL) reduced the PHE-, but not the caffeine-induced contraction. In Ca(2+)-free and high K(+) (75 mM) medium, the contractions produced by CaCl(2) or BaCl(2) were reduced or even abolished by EOAC and NP at 100 and 600 µg/mL, respectively. EOAC and NP (both at 10-1000 µg/mL) also relaxed the contraction evoked by phorbol dibutyrate (IC(50)=52.66 [10.82-94.64] and 39.13 [31.55-46.72] µg/mL, respectively). It is concluded that NP has a myogenic endothelium-independent vasorelaxant effects and appears to be the active principle of the EOAC. Vasorelaxant effect induced by both EOAC and NP is preferential to receptor-activated pathways and it appears to occur intracellularly more than a superficial action restricted to the membrane environment such as a simple blocking activity on a given receptor or ion channel.
Assuntos
Derivados de Benzeno/farmacologia , Lauraceae , Artéria Mesentérica Superior/efeitos dos fármacos , Óleos Voláteis/farmacologia , Vasodilatadores/farmacologia , Animais , Cafeína/farmacologia , Cálcio/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Técnicas In Vitro , Masculino , Artéria Mesentérica Superior/fisiologia , Fenilefrina/farmacologia , Casca de Planta , Ratos , Ratos Endogâmicos SHR , Vasoconstritores/farmacologiaRESUMO
BACKGROUND: Blood flow volume in the superior mesenteric artery (SMA) measured by pulsed Doppler has been used in adults to evaluate Crohn disease but has not been utilized in children and adolescents. OBJECTIVE: To establish a cutoff point for normal SMA blood flow using pulsed Doppler US measurement in healthy children and adolescents. MATERIALS AND METHODS: The study included healthy volunteers from an urban community, divided into two age groups, children (5-9 years) and adolescents (10-17 years). Anthropometric measurements included waist circumference and body surface area classified according to the z-score of body mass index. Heart rate, blood pressure, oxygen saturation and temperature were measured immediately before US evaluation. RESULTS: The average age of the 60 participants was 12.2 years. Of these, 21 (35%) were ages 5-9 years and 39 (65%) were ages 10-17 years; 21 (35%) were boys. Findings of the two examiners coincided for 58 of the 60 (96.7%) participants. SMA blood flow was significantly lower in the children (mean ± SD = 556 ± 122 ml/min) than in adolescents (mean ± SD 775 ± 311 ml/min) (P < 0.001). SMA blood flow showed statistically significant positive associations with body surface area. CONCLUSION: We found that superior mesenteric artery blood flow is significantly lower in children than in adolescents and is associated with body surface area.
Assuntos
Determinação do Volume Sanguíneo/métodos , Artéria Mesentérica Superior/diagnóstico por imagem , Artéria Mesentérica Superior/fisiologia , Ultrassonografia Doppler Dupla/métodos , Adolescente , Velocidade do Fluxo Sanguíneo/fisiologia , Volume Sanguíneo/fisiologia , Criança , Feminino , Humanos , Masculino , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
To study whether treatment with L-arginine (ARG), a substrate of nitric oxide biosynthesis, attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), rabbits treated with ARG (100 mgxkg(-1), intravenously) or saline solution (SS) prior to I (60 minutes) by occlusion of superior mesenteric artery and/or during R (120 minutes). After I or I/R, 2-cm jejunal segments were isolated and mounted in an organ bath to study of neurogenic contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained (hematoxylin and eosin) for analysis by optical microscopy. Compared to the sham group, jejunal contractions were similar in I + ARG, but reduced in I + SS, I/R + SS, and I/R + ARG groups. The jejunal enteric nerves were damaged in I + SS, I/R + SS, and I/R + ARG, but not in I + ARG group, suggesting that ARG can attenuate intestinal dysfunctions due to I, but not to R.
Assuntos
Arginina/farmacologia , Intestinos/irrigação sanguínea , Óxido Nítrico/biossíntese , Traumatismo por Reperfusão/prevenção & controle , Animais , Arginina/uso terapêutico , Circulação Sanguínea , Veia Femoral/fisiologia , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Isquemia/fisiopatologia , Jejuno/irrigação sanguínea , Jejuno/efeitos dos fármacos , Jejuno/patologia , Artéria Mesentérica Superior/fisiologia , Coelhos , Reperfusão/efeitos adversos , Traumatismo por Reperfusão/fisiopatologiaRESUMO
To study whether treatment with the beta-blocker atenolol (AT) attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), rabbits were treated with AT (1 mg.kg(-1), introvenously) or saline solution (SS) prior to I (60 minutes), which was produced by occlusion of the superior mesenteric artery, and/or R (120 minutes). After I or I/R, 2-cm jejunal segments were mounted in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained hematoxylin and eosin for analysis by optical microscopy. Compared to the sham group, the jejunal contractions were similar in the I + AT and the I/R + AT groups, but reduced in the I + SS and the I/R + SS groups. The jejunal enteric nerves were damaged in the I + SS and the I/R + SS groups, but not in the I + AT and the I/R + AT. These results suggest that AT may attenuate intestinal dysfunction caused by I and I/R.
Assuntos
Atenolol/uso terapêutico , Enteropatias/tratamento farmacológico , Intestinos/irrigação sanguínea , Jejuno/fisiologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Circulação Sanguínea , Estimulação Elétrica , Enteropatias/etiologia , Jejuno/irrigação sanguínea , Jejuno/efeitos dos fármacos , Masculino , Artéria Mesentérica Superior/fisiologia , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Cloreto de Potássio/farmacologia , CoelhosRESUMO
To study if the treatment with adenosine (ADO), an agonist of adenosine receptors, attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), we treated rabbits with ADO (15 mg x kg(-1), intravenously) or saline solution (SS) to I (60 minutes) before occlusion of superior mesenteric artery and/or R (120 min). After I or I/R, isolated jejunal segments (2 cm) were mounted in an organ bath to study nerve-mediated contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained (hematoxylin and eosin) for analysis by optical microscopy. Compared to the sham group, the jejunal contractions were similar in I + ADO, but reduced in I + SS, I/R + SS, and I/R + ADO groups. We concluded that the jejunal enteric nerves were damaged in I + SS, I/R + SS, and I/R + ADO, but not in I + ADO group. These results suggested that ADO attenuated intestinal dysfunction due to I, but not to R.
Assuntos
Adenosina/farmacologia , Intestinos/irrigação sanguínea , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Circulação Sanguínea , Estimulação Elétrica , Veia Femoral/efeitos dos fármacos , Veia Femoral/fisiologia , Jejuno/irrigação sanguínea , Jejuno/efeitos dos fármacos , Jejuno/fisiologia , Masculino , Artéria Mesentérica Superior/fisiologia , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Cloreto de Potássio/farmacologia , Agonistas do Receptor Purinérgico P1 , Coelhos , Cloreto de Sódio/farmacologiaRESUMO
This study was performed to investigate the mechanisms involved in the vasorelaxation induced by mesoionic 2-(4-chlorophenyl)-3-methyl-4-(4-methoxyphenyl)-1;3-thiazolium-5-thyolate (CMMTT), a newly synthesized mesoionic compound, in rat superior mesenteric arteries. In phenylephrine (10 microM)-pre-contracted mesenteric rings, CMMTT (10(-14) - 10(-6) M) induced a concentration-dependent relaxation [pD(2) = 10.26 +/- 0.05, E(max) = 80.8 +/- 5.8%], and this effect was almost abolished after either removal of the vascular endothelium [E(max) = 17.7 +/- 4.2%, P<0.001], removal of the vascular endothelium plus100 microM N(omega)-nitro-L-arginine methyl esther (L-NAME) [E(max) = 21.0 +/- 2.0 %, P<0.001], or after pre-treatment of the rings with 100 microM L-NAME [E(max) = 13.3 +/- 2.4%, P<0.001] or 10 microM 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) [E(max) = 13.6 +/- 4.8%, P<0.001]. However, endothelium-dependent relaxation induced by CMMTT was not significantly modified after 1 microM indomethacin plus 1 nM atropine [pD(2) = 11.12 +/- 0.08, E(max) = 73.8 +/- 5.15%] or 100 nM charybdotoxin (ChTX) plus 100 nM apamin [pD(2) = 10.89 +/- 0.08, E(max) = 58.91 +/- 9.8%]. In mesenteric rings, CMMTT (10(-6) M) was able to increase nitric oxide (NO)(x) levels, and this effect was abolished after removal of the vascular endothelium. In conclusion, the present study, using combined functional and biochemical approaches, demonstrated that CMMTT induced a significant vasorelaxant effect, almost completely mediated by the endothelium, likely via NO release and activation of the NO-cGMP pathway.
Assuntos
Endotélio Vascular/fisiologia , Óxido Nítrico/fisiologia , Tiazóis/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia , Vasodilatadores/farmacologia , Animais , Fatores Biológicos/fisiologia , Interpretação Estatística de Dados , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/farmacologia , Masculino , Artéria Mesentérica Superior/efeitos dos fármacos , Artéria Mesentérica Superior/metabolismo , Artéria Mesentérica Superior/fisiologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I/metabolismo , Oxidiazóis/farmacologia , Fenilefrina/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Vasoconstritores/farmacologiaRESUMO
Proanthocyanidins are condensed tannins present in fruits, vegetables, and flowers, consumed in the human diet. These compounds are believed to decrease coronary heart disease. The present study was designed to investigate the relaxing effects of a proanthocyanidin-rich fraction (PRF) obtained from Croton celtidifolius BAILL (Euphorbiaceae) barks in rat mesenteric arterial bed (MAB) and isolated mesenteric artery (MA). In the MAB pre-contracted with phenylephrine (Phe), PRF (0.1 - 100 microg) induced a concentration-dependent relaxation of 73% (compared to the control). This effect was significantly reduced by the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine (L-NOARG) or high K(+) solution and completely abolished in vessels perfused with KCl plus L-NOARG. However, the vasorelaxant effect was not altered by indomethacin, atropine, yohimbine, pyrilamine, or K(+)-channel blockers: BaCl(2), glibenclamide, ouabain, and 4-aminopyridine. In isolated MA pre-contracted with Phe, PRF also induced a concentration-dependent relaxation (0.1 - 30 microg/mL), which was in turn inhibited by endothelial removal, guanylyl cyclase inhibitor 1H[1,2,3]oxadiazolo[4,3-alpha]quinoxalin, charybdotoxin (ChTx), and ChTx plus apamin. Moreover, the relaxant effect was not altered by HOE140 and apamin given alone. The present study demonstrates that the vasorelaxing effect of PRF is dependent upon the NO-cGMP pathway in combination with hyperpolarization due to activation of Ca(2+)-dependent K(+) channels.
Assuntos
Croton/química , Artéria Mesentérica Superior/efeitos dos fármacos , Proantocianidinas/farmacologia , Vasodilatadores/farmacologia , Animais , GMP Cíclico/fisiologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Técnicas In Vitro , Masculino , Artéria Mesentérica Superior/fisiologia , Óxido Nítrico/fisiologia , Casca de Planta/química , Canais de Potássio Cálcio-Ativados/fisiologia , Ratos , Ratos WistarRESUMO
The aim of this study was to investigate the vasorelaxant effect induced by diosgenin in superior mesenteric rings. In rings pre-contracted with phenylephrine (10 microM), diosgenin caused concentration-dependent relaxations [EC(50) = (3.3 +/- 1.2) x 10(- 4)M, E(max) = 94.2 +/- 2.6 %]. Vascular relaxation induced by diosgenin was significantly inhibited after removal of the endothelium (E(max) = 46 +/- 8.8%, p < 0.001) or after pre-treatment of the rings with N-nitro-L-arginine methyl esther (l-NAME) 100 or 300 microM (E(max) = 35.3 +/- 4%; 28.1 +/- 3.3%, respectively, p < 0.001), atropine 1 microM (E(max) = 24.6 +/- 3.4%, p < 0.001), hydroxocobalamin 30 microM (E(max) = 54.0 +/- 9.6%, p < 0.001), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) 10 microM (E(max) = 46.0 +/- 8.0%, p < 0.001) or indomethacin 1 microM (E(max) = 22.6 +/- 11.8%, p < 0.001). Vasorelaxation evoked by diosgenin was significantly inhibited after pre-treatment of preparations with both selective and non-selective inhibitors of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels, iberiotoxin 100 nM or tetraethylammonium (TEA) 1mM, respectively (E(max) = 62.5 +/- 9.1%; 65.7 +/- 1.1%, p < 0.001). Conversely, in endothelium-denuded vessels, none of BK(Ca) channel blockers modified the relaxant effect induced by diosgenin. In mesenteric endothelial cells loaded with FURA-2 diosgenin was able to increase intracellular calcium concentrations, which were significantly decreased by atropine 1 microM. In addition, in isolated mesenteric rings, diosgenin induced marked increase in nitric oxide (NO) levels, which was completely abolished after functional endothelium removal. The results obtained here demonstrated that diosgenin-induced relaxation appears to involve endothelial muscarinic receptor activation with increase in intracellular calcium concentrations and consequent release of endothelium-derived relaxing factors (EDRFs), mainly NO and cyclooxygenase derivatives, which activate BK(Ca) channels. Nevertheless, further studies are necessary to clearly elucidate residual endothelium-independent relaxation induced by diosgenin.
Assuntos
Diosgenina/farmacologia , Artéria Mesentérica Superior/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Fatores Relaxantes Dependentes do Endotélio/fisiologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/fisiologia , Masculino , Artéria Mesentérica Superior/fisiologia , Óxido Nítrico/fisiologia , Fenilefrina/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Prostaglandina-Endoperóxido Sintases/fisiologia , Ratos , Ratos WistarRESUMO
Caesalpinia ferrea is a plant very used in the folk medicine for treatment of several diseases, such as diabetes. This study investigated the cardiovascular effects of the aqueous extract from stem bark of C. ferrea (AECF). In non-anesthetized rats, AECF (10, 20, 40, 60 and 80 mg/kg; i.v.) induced hypotension (-9+/-1;-12+/-1;-14+/-1; -20+/-3 and -51+/-6%; respectively) and tachycardia (6+/-1; 8+/-1; 12+/-2; 14+/-2 and 26+/-3%; respectively). Hypotension was not affected after atropine or L-NAME. Furthermore, AECF (40 mg/kg) induced atrioventricular block and extrasystoles, which was not affected after atropine. In intact rings of the rat mesenteric artery, AECF (0.001-30 mg/ml, n=6) induced relaxations of phenylephrine tonus (Emax=110+/-4%), which was not changed after the removal of endothelium (Emax=113+/-9%). In rings without endothelium pre-contracted with KCl 80 mM, phenylephrine plus KCl 20 mM or phenylephrine plus glibenclamide, the curve to AECF was significantly attenuated (Emax=24+/-4%, 70+/-5% and 62+/-7%, respectively, n=6), but was not affected in the presence of tetraethylammonium or 4-aminopyridine (Emax=125+/-15% and 114+/-7%, respectively, n=6). These results demonstrate that AECF induces hypotension associated to tachycardia; however, in dose of 40 mg/kg, AECF induces transient bradyarrhythmias. Furthermore, AECF induces vasodilatation in rat mesenteric artery which appears to be mediated by ATP-sensitive K+ channel openings.
Assuntos
Trifosfato de Adenosina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Caesalpinia , Frequência Cardíaca/efeitos dos fármacos , Extratos Vegetais/farmacologia , Canais de Potássio/efeitos dos fármacos , Animais , Atropina/farmacologia , Eletrocardiografia/efeitos dos fármacos , Técnicas In Vitro , Masculino , Artéria Mesentérica Superior/efeitos dos fármacos , Artéria Mesentérica Superior/fisiologia , NG-Nitroarginina Metil Éster/farmacologia , Canais de Potássio/fisiologia , RatosRESUMO
The vasorelaxantion of the aqueous fraction of the hydroalcoholic extract of the Sida cordifolia leaves (AFSC) was evaluated in this work. In rat superior mesenteric artery, AFSC (3-1000 microg/mL) induced relaxation of phenylephrine-induced contractions. This effect was significantly attenuated after removal of the endothelium, after atropine (1 microM), L-NAME (100 microM), indomethacin (10 microM), high K+ (20 mM), tetraethylammonium (1 microM), a K(Ca) blocker, apamin (1 microM), a SK(Ca) blocker and ChTX (0.1 microM), a BK(Ca) blocker, however, it was not affected after glibenclamide (10 microM), an KATP blocker, and 4-aminopyridine (1 microM), a Kv blocker. ChTX (0.1 microM) was able to induce an additional inhibition of the vasorelaxation induced by AFSC in the presence of L-NAME plus indomethacin. The vasorelaxation induced by AFSC in the presence of L-NAME plus indomethacin plus ChTX was not different from that induced by AFSC in rings without endothelium. In conclusion, the results show that endothelium-derived factors (mainly NO, PGI2) and K+ channels (BK(Ca) and SK(Ca)) play a crucial role in the vasorelaxation induced by AFSC in the rat superior mesenteric artery.
Assuntos
Endotélio Vascular/fisiologia , Malvaceae/química , Artéria Mesentérica Superior/fisiologia , Músculo Liso Vascular/fisiologia , Canais de Potássio/fisiologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Charibdotoxina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Técnicas In Vitro , Indometacina/farmacologia , Artéria Mesentérica Superior/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Relaxamento Muscular/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Extratos Vegetais/farmacologia , Folhas de Planta/química , Canais de Potássio/efeitos dos fármacos , Cloreto de Potássio/farmacologia , RatosRESUMO
INTRODUCTION: Increased intramucosal-arterial carbon dioxide tension (PCO2) difference (DeltaPCO2) is common in experimental endotoxemia. However, its meaning remains controversial because it has been ascribed to hypoperfusion of intestinal villi or to cytopathic hypoxia. Our hypothesis was that increased blood flow could prevent the increase in DeltaPCO2. METHODS: In 19 anesthetized and mechanically ventilated sheep, we measured cardiac output, superior mesenteric blood flow, lactate, gases, hemoglobin and oxygen saturations in arterial, mixed venous and mesenteric venous blood, and ileal intramucosal PCO2 by saline tonometry. Intestinal oxygen transport and consumption were calculated. After basal measurements, sheep were assigned to the following groups, for 120 min: (1) sham (n = 6), (2) normal blood flow (n = 7) and (3) increased blood flow (n = 6). Escherichia coli lipopolysaccharide (5 microg/kg) was injected in the last two groups. Saline solution was used to maintain blood flood at basal levels in the sham and normal blood flow groups, or to increase it to about 50% of basal in the increased blood flow group. RESULTS: In the normal blood flow group, systemic and intestinal oxygen transport and consumption were preserved, but DeltaPCO2 increased (basal versus 120 min endotoxemia, 7 +/- 4 versus 19 +/- 4 mmHg; P < 0.001) and metabolic acidosis with a high anion gap ensued (arterial pH 7.39 versus 7.35; anion gap 15 +/- 3 versus 18 +/- 2 mmol/l; P < 0.001 for both). Increased blood flow prevented the elevation in DeltaPCO2 (5 +/- 7 versus 9 +/- 6 mmHg; P = not significant). However, anion-gap metabolic acidosis was deeper (7.42 versus 7.25; 16 +/- 3 versus 22 +/- 3 mmol/l; P < 0.001 for both). CONCLUSIONS: In this model of endotoxemia, intramucosal acidosis was corrected by increased blood flow and so might follow tissue hypoperfusion. In contrast, anion-gap metabolic acidosis was left uncorrected and even worsened with aggressive volume expansion. These results point to different mechanisms generating both alterations.
Assuntos
Acidose/prevenção & controle , Endotoxemia/complicações , Infecções por Escherichia coli/complicações , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/metabolismo , Equilíbrio Ácido-Base , Acidose/metabolismo , Animais , Dióxido de Carbono/sangue , Dióxido de Carbono/metabolismo , Interpretação Estatística de Dados , Modelos Animais de Doenças , Endotoxemia/sangue , Escherichia coli , Lipopolissacarídeos/administração & dosagem , Artéria Mesentérica Superior/fisiologia , Mesentério/irrigação sanguínea , Oxigênio/sangue , Oxigênio/metabolismo , Consumo de Oxigênio , OvinosRESUMO
RACIONAL: Os sintomas gastrointestinais são freqüentes no diabetes mellitus e podem estar relacionados com o estresse oxidativo, que é definido pelo desequilíbrio entre os sistemas pró-oxidante e o antioxidante. OBJETIVO: Avaliar algumas das alterações gastrointestinais no modelo de diabetes mellitus, como o estresse oxidativo no estômago e no fígado de animais diabéticos e o fluxo sangüíneo na artéria mesentérica superior em diferentes tempos de estudo. MATERIAL E MÉTODOS: Os parâmetros utilizados para verificar o estresse oxidativo no fígado e no estômago foram a mensuração da lipoperoxidação, através das técnicas das substâncias reativas ao ácido tiobarbitúrico e da quimiluminescência e a avaliação da atividade das enzimas antioxidantes catalase, superóxido dismutase e glutationa transferase. Utilizaram-se ratos machos Wistar, pesando entre 250-350 g, que foram divididos em quatro grupos: grupo I - 7 dias de diabetes, grupo II- 30 dias de diabetes, grupo III - 60 dias de diabetes e grupo IV - 90 dias de diabetes. O diabetes foi induzido por administração de estreptozotocina 70 mg/kg intraperitonialmente. RESULTADOS: Houve aumento significativo na lipoperoxidação no estômago e no fígado de animais diabéticos somente no tempo de 90 dias. No estômago, foi encontrada significativa diminuição na atividade das enzimas antioxidantes catalase e glutationa transferase. No fígado, somente a enzima glutationa transferase apresentou diminuição significativa. Houve aumento no fluxo da artéria mesentérica superior dos animais diabéticos com 90 dias, quando comparados aos animais-controle. CONCLUSÕES: É possível supor que o aumento no estresse oxidativo no estômago e no fígado e a alteração no fluxo sangüíneo da artéria mesentérica superior sejam influenciados pelo tempo de diabetes e pela hiperglicemia encontrada nos animais estudados, o que determinaria as alterações gastrointestinais.
Assuntos
Animais , Masculino , Ratos , Diabetes Mellitus Experimental/metabolismo , Artéria Mesentérica Superior/fisiologia , Estresse Oxidativo , Catalase/metabolismo , Modelos Animais de Doenças , Diabetes Mellitus Experimental/fisiopatologia , Mucosa Gástrica/enzimologia , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos , Fígado/enzimologia , Ratos Wistar , Fluxo Sanguíneo RegionalRESUMO
1. Herein, we report the effects of acute or chronic forced swimming on vascular responsiveness to angiotensin (Ang) II. 2. The possible involvement of locally produced substances, such as nitric oxide (NO) and prostanoids, in these effects were studied in rat thoracic aorta and superior mesenteric arteries. 3. Chronic, but not acute, swimming reduced the efficacy (maximal effect; Emax) of AngII in thoracic aorta and mesenteric arteries, either with intact or denuded endothelium. 4. The efficacy of AngII was reduced in the presence of indomethacin in mesenteric arteries, but not in the aorta, from either control or chronically stressed rats. 5. Treatment with NG-monomethyl-l-arginine reversed the effect of chronic stress on the response to AngII, suggesting that chronic stress may increase non-endothelial NO activity in both the aorta and mesenteric arteries. 6. The effects of acute and chronic stress on vascular reactivity were selective for AngII because no changes were observed on the effects of phenylephrine.
Assuntos
Músculo Liso Vascular/metabolismo , Óxido Nítrico/metabolismo , Condicionamento Físico Animal/métodos , Estresse Fisiológico/metabolismo , Natação/fisiologia , Angiotensina II/antagonistas & inibidores , Angiotensina II/farmacologia , Animais , Aorta Torácica/citologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/lesões , Corticosterona/sangue , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/lesões , Endotélio Vascular/fisiologia , Indometacina/farmacologia , Masculino , Artéria Mesentérica Superior/efeitos dos fármacos , Artéria Mesentérica Superior/fisiologia , Músculo Liso Vascular/química , Músculo Liso Vascular/efeitos dos fármacos , Fenilefrina/farmacologia , Condicionamento Físico Animal/fisiologia , Ratos , Ratos Wistar , ômega-N-Metilarginina/farmacologiaRESUMO
Peripheral treatment with the cholinergic agonist pilocarpine induces intense salivation that is inhibited by central injections of the alpha2-adrenergic/imidazoline receptor agonist moxonidine. Salivary gland blood flow controlled by sympathetic and parasympathetic systems may affect salivation. We investigated the changes in mean arterial pressure (MAP) and in the vascular resistance in the submandibular/sublingual gland (SSG) artery, superior mesenteric (SM) artery and low abdominal aorta (hindlimb) in rats treated with intraperitoneal (i.p.) pilocarpine alone or combined with intracerebroventricular (i.c.v.) moxonidine. Male Holtzman rats with stainless steel cannula implanted into lateral ventricle (LV) and anesthetized with urethane were used. Pilocarpine (4 micromol/kg of body weight) i.p. reduced SSG vascular resistance (-50+/-13% vs. vehicle: 5+/-3%). Pilocarpine i.p. also increased mesenteric vascular resistance (15+/-5% vs. vehicle: 2+/-3%) and MAP (16+/-3 mmHg, vs. vehicle: 2+/-3 mmHg). Moxonidine (20 nmol) i.c.v. increased SSG vascular resistance (88+/-12% vs. vehicle: 7+/-4%). When injected 15 min following i.c.v. moxonidine, pilocarpine i.p. produced no change on SSG vascular resistance. Pilocarpine-induced pressor responses and increase in mesenteric vascular resistance were not modified by i.c.v. moxonidine. The treatments produced no change in heart rate (HR) and hindlimb vascular resistance. The results show that (1) i.p. pilocarpine increases mesenteric vascular resistance and MAP and reduces salivary gland vascular resistance and (2) central moxonidine increases salivary gland vascular resistance and impairs pilocarpine-induced salivary gland vasodilatation. Therefore, the increase in salivary gland vascular resistance may play a role in the anti-salivatory response to central moxonidine.