RESUMO
AIMS: A historic of preeclampsia (PE) has been associated with cardiovascular disease (CVD) in women. There are substantial evidences that cardiovascular changes resulting from PE can persist even after pregnancy end. Therefore, the aims was to evaluate the prevalence of myocardial hypertrophy in young women 12 months after PE event as well as try to identify risk factors for these changes. MATERIALS AND METHODS: Single-center observational prospective cross-sectional study that included 118 consecutive patients after 12 months of PE. Clinical and laboratory evaluations, echocardiogram were performed. Myocardial hypertrophy (LVH) was defined as an index myocardial mass ≥ 45 g/m2.7, for women. Classical risk factors for CVD were considered. Analysis included linear or logistic regression and Spearman's correlation coefficient. Significance level of 5 %. KEY FINDINGS: Systemic arterial hypertension (SAH) was identified in 52 patients (44 %), overweight/obesity (OOB) in 82 (69 %), dyslipidemia in 68 (57 %) and metabolic syndrome in 47 patients (40 %). LVH was present in 35 cases (29 %) and associated with OOB (OR = 4.51; CI95%:1.18-17.17, p < 0.001), in a model corrected for age and SAH diagnosis. When only the metabolic syndrome components were analyzed, in the multiple logistic regression model, the abdominal circumference was the only clinical variable associated with LVH (OR = 17.65; CI95%:3.70-84.17; p < 0.001). SIGNIFICANCE: It was observed a high prevalence of ventricular hypertrophy in young women with a history of pre-eclampsia. This condition was associated with the presence of obesity.
Assuntos
Fatores de Risco de Doenças Cardíacas , Pré-Eclâmpsia , Humanos , Feminino , Pré-Eclâmpsia/epidemiologia , Gravidez , Adulto , Estudos Transversais , Estudos Prospectivos , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Cardiomegalia/epidemiologia , Cardiomegalia/etiologia , Prevalência , Obesidade/complicações , Obesidade/epidemiologia , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/etiologia , Adulto Jovem , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Hipertensão/epidemiologia , Hipertensão/complicaçõesRESUMO
Fabry disease (FD) (Anderson-Fabry disease, OMIM 301500) is a genetic disorder caused by a pathogenic variant in the GLA gene on chromosome Xq22 that produces a deficiency in the lysosomal enzyme alpha-galactosidase A. It is transmitted as an X-linked trait, although de novo mutations have been described. The objective of this report is to describe the clinical characteristics of a patient with FD who is a carrier of a mutation not previously studied, in order to provide information on the genotype-phenotype correlation in this pathology. 38-year-old patient who consulted Neurology for positional vertigo. He also reported acroparesthesia, anhidrosis, heat intolerance and episodes of abdominal pain, with postprandial discomfort from 10 years of age. Physical examination showed horizonto-rotatory nystagmus in both looks, the rest of the neurological evaluation did not present abnormalities. The presence of umbilical and thighs angiokeratomas was identified. Determination of Alpha-Galactosidase in blood was requested: 0.34 µmol/l/h (2.10-10.51 µmol/l/h). Genetic analysis detected a deletion of a guanine at position 448, in exon 3 of the GLA gene (c.448delG). This mutation was considered to be pathogenic, confirming the diagnosis of FD, although it is not described in the data bases. Genetic counseling and a family pedifree study were performed without finding relatives with this variant of the GLA gene or a family history of FD, which suggests a de novo mutation.
RESUMO
BACKGROUND AND AIMS: Although many studies have reported the effects of AT1 receptor on dietary salt overload, the role of AT2 receptor in this model is far from completely elucidated. The present study aimed to better understand the role of AT2 receptor in cardiac structure alterations in response to chronic high salt intake in rats. METHODS AND RESULTS: Male Wistar rats were fed a normal or high salt diet from weaning until 18 weeks of age. Both groups were subdivided into two groups. Starting at 7 weeks of age, rats were treated with or without compound 21 (0.3 mg/kg/day, n = 16), an AT2 receptor agonist. Metabolics and structural parameters were measured. BP, transverse cardiomyocyte and intersticial fibrose was higher in animals fed with high salt diet compared with normal salt fed animals. CONCLUSION: Compound 21 prevented the development of cardiac hypertrophy and fibrosis, reduced the increase in blood pressure and prevented the lower weight gain in animals fed a high salt diet.
Assuntos
Cardiomegalia/prevenção & controle , Fármacos Cardiovasculares/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Receptor Tipo 2 de Angiotensina/agonistas , Cloreto de Sódio na Dieta , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Modelos Animais de Doenças , Fibrose , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Masculino , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos Wistar , Receptor Tipo 2 de Angiotensina/metabolismo , Transdução de Sinais , Aumento de Peso/efeitos dos fármacosRESUMO
Abstract Bone morphogenetic protein-4 (BMP4) is a member of the bone morphogenetic protein family which plays an important role in bone formation, inflammation and cardiac hypertrophy. The aim of this study was to investigate the underlying molecular mechanism that BMP4-induced cardiomyocyte hypertrophy. H9c2 cells were used to measure cell surface area and protein synthesis. Western blot was used to examine hypertrophic marker brain natriuretic peptide (BNP) protein expression and phosphorylation of ERK1/2. The results exhibited that cell surface area, protein synthesis and BNP protein expression were increased with BMP4 treatment. While PD98059 inhibited these effects of BMP4. In addition, BMP4 treatment increased phosphorylation of ERK1/2 in a time- and dose-dependent manner. PD98059 treatment decreased phosphorylation of ERK1/2 that was increased by BMP4. These results suggest that BMP4 induces cardiomyocyte hypertrophy through the activation of ERK1/2 cell signaling pathway.
Assuntos
Cardiomegalia/induzido quimicamente , Proteína Morfogenética Óssea 4/administração & dosagem , Western Blotting/instrumentação , Proteína Quinase 3 Ativada por Mitógeno , Via de Sinalização WntRESUMO
We aimed to investigate the effect of etanercept, a tumor necrosis factor-α (TNF-α) inhibitor, on rat cardiomyocyte hypertrophy and its underlying mechanism. Primary neonatal rat cardiomyocytes were isolated from Sprague-Dawley rats. The model of rat cardiomyocyte hypertrophy was induced by endothelin, and then treated with different concentrations of etanercept (1, 10, and 50 μM). After treatment, cell counts, viability and cell apoptosis were evaluated. The mRNA levels of myocardial hypertrophy marker genes, including atrial natriuretic factor (ANF), matrix metalloproteinase (MMP)-9 and MMP-13, were detected by qRT-PCR, and the expressions of apoptosis-related proteins (Bcl-2 and Bax) were measured by western blotting. The protein levels of transforming growth factor-β1 (TGF-β1), interleukin (IL)-1β, IL-6, leukemia inhibitory factor (LIF) and cardiotrophin-1 (CT-1) were determined using enzyme linked immunosorbent assay (ELISA) kits. In the present study, TNF-α level in cardiomyocytes with hypertrophy was significantly enhanced (P<0.05). Compared to the model group, cell number and viability were significantly increased and ratio of apoptotic cells was reduced by etanercept (P<0.05, P<0.01, or P<0.001). In addition, etanercept remarkably reduced the mRNA levels of ANF, MMP-9 and MMP-13, inhibited the expression of Bax, and increased the expression of Bcl-2 compared to the model group (P<0.05). ELISA results further showed that etanercept lowered the levels of IL-1β, IL-6, LIF and CT-1 but not TGF-β1 compared to the model group (P<0.05). Etanercept may protect rat cardiomyocytes from hypertrophy by inhibiting inflammatory cytokines secretion and cell apoptosis.
Assuntos
Animais , Anti-Inflamatórios não Esteroides/farmacologia , Cardiomegalia/metabolismo , Etanercepte/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Fator Natriurético Atrial/metabolismo , Cardiomegalia/induzido quimicamente , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/efeitos dos fármacos , Modelos Animais de Doenças , Inflamação/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Miócitos Cardíacos/metabolismo , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We investigated whether Ca2+/calmodulin-dependent kinase II (CaMKII) and calcineurin (CaN) are involved in myocardial hypertrophy induced by tumor necrosis factor α (TNF-α). The cardiomyocytes of neonatal Wistar rats (1-2 days old) were cultured and stimulated by TNF-α (100 μg/L), and Ca2+ signal transduction was blocked by several antagonists, including BAPTA (4 µM), KN-93 (0.2 µM) and cyclosporin A (CsA, 0.2 µM). Protein content, protein synthesis, cardiomyocyte volumes, [Ca2+]i transients, CaMKIIδB and CaN were evaluated by the Lowry method, [³H]-leucine incorporation, a computerized image analysis system, a Till imaging system, and Western blot analysis, respectively. TNF-α induced a significant increase in protein content in a dose-dependent manner from 10 µg/L (53.56 µg protein/well) to 100 μg/L (72.18 µg protein/well), and in a time-dependent manner from 12 h (37.42 µg protein/well) to 72 h (42.81 µg protein/well). TNF-α (100 μg/L) significantly increased the amplitude of spontaneous [Ca2+]i transients, the total protein content, cell size, and [³H]-leucine incorporation in cultured cardiomyocytes, which was abolished by 4 µM BAPTA, an intracellular Ca2+ chelator. The increases in protein content, cell size and [³H]-leucine incorporation were abolished by 0.2 µM KN-93 or 0.2 µM CsA. TNF-α increased the expression of CaMKIIδB by 35.21% and that of CaN by 22.22% compared to control. These effects were abolished by 4 µM BAPTA, which itself had no effect. These results suggest that TNF-α induces increases in [Ca2+]i, CaMKIIδB and CaN and promotes cardiac hypertrophy. Therefore, we hypothesize that the Ca2+/CaMKII- and CaN-dependent signaling pathways are involved in myocardial hypertrophy induced by TNF-α.
Assuntos
Animais , Ratos , Calcineurina/metabolismo , /metabolismo , Cardiomegalia/metabolismo , Miócitos Cardíacos/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Animais Recém-Nascidos , Células Cultivadas , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Ratos Wistar , Transdução de SinaisRESUMO
Ventricular hypertrophy is one of the major myocardial responses to pressure overload (PO). Most studies on early myocardial response focus on the days or even weeks after induction of hypertrophic stimuli. Since mechanotransduction pathways are immediately activated in hearts undergoing increased work load, it is reasonable to infer that the myocardial gene program may be regulated in the first few hours. In the present study, we monitored the expression of some genes previously described in the context of myocardial hypertrophic growth by using the Northern blot technique, to estimate the mRNA content of selected genes in rat myocardium for the periods 1, 3, 6, 12 and 48 h after PO stimuli. Results revealed an immediate switch in the expression of genes encoding alpha and beta isoforms of myosin heavy chain, and up-regulation of the cardiac isoform of alpha actin. We also detected transitory gene regulation as the increase in mitochondrial cytochrome c oxidase 1 gene expression, parallel to down-regulation of genes encoding sarco(endo)plasmic reticulum Ca(+2) ATPase and sodium-calcium exchanger. Taken together, these results indicate that initial myocardial responses to increased work load include alterations in the contractile properties of sarcomeres and transitory adjustment of mitochondrial bioenergetics and calcium availability.
RESUMO
Ventricular hypertrophy is one of the major myocardial responses to pressure overload (PO). Most studies on early myocardial response focus on the days or even weeks after induction of hypertrophic stimuli. Since mechanotransduction pathways are immediately activated in hearts undergoing increased work load, it is reasonable to infer that the myocardial gene program may be regulated in the first few hours. In the present study, we monitored the expression of some genes previously described in the context of myocardial hypertrophic growth by using the Northern blot technique, to estimate the mRNA content of selected genes in rat myocardium for the periods 1, 3, 6, 12 and 48 h after PO stimuli. Results revealed an immediate switch in the expression of genes encoding alpha and beta isoforms of myosin heavy chain, and up-regulation of the cardiac isoform of alpha actin. We also detected transitory gene regulation as the increase in mitochondrial cytochrome c oxidase 1 gene expression, parallel to down-regulation of genes encoding sarco(endo)plasmic reticulum Ca+2 ATPase and sodium-calcium exchanger. Taken together, these results indicate that initial myocardial responses to increased work load include alterations in the contractile properties of sarcomeres and transitory adjustment of mitochondrial bioenergetics and calcium availability.
RESUMO
Fundamento: Ao migrarem para as Américas, os japoneses submeteram-se a processo de ocidentalização, com estilo de vida, especialmente dieta, muito diferente, podendo explicar o aumento de diabete melito (DM), síndrome metabólica (SM) e doenças cardiovasculares. Objetivo: Analisar a presença de necrose miocárdica e hipertrofia ventricular esquerda (HVE) pelo ECG e sua relação com DM e SM em população de nipo-brasileiros. Métodos: Estudo transversal que avaliou 1.042 nipo-brasileiros acima de 30 anos, 202 nascidos no Japão (isseis) e 840 nascidos no Brasil (nisseis), provenientes da segunda fase do estudo Japanese-Brazilian Diabetes Study Group iniciado em 2000. A SM foi definida pelos critérios da NCEP-ATP III modificados para os japoneses. A presença de DM e SM se associou ao encontro de necrose miocárdica pelo critério de Minnesota e de HVE pelo critério de Perugia no ECG. Utilizou-se o método estatístico do qui-quadrado para rejeição da hipótese de nulidade. Resultados: Dos 1.042 participantes 35,3% tinham DM (38,6% entre os isseis e 34,5% nos nisseis); 51,8% tinham SM (59,4% nos isseis e 50,0% nos nisseis). A presença de zona inativa nos isseis diabéticos não foi estatisticamente significante quando comparada com os não-diabéticos, porém entre os nisseis diabéticos a zona inativa estava presente em 7,5%. Houve correlação estatisticamente significante entre a SM e HVE nos isseis e nisseis. Conclusão: Distúrbios metabólicos tiveram alta prevalência em nipo-brasileiros com correlações significantes com necrose e hipertrofia pelo ECG.
Background: When the Japanese immigrated to the Americas, they were subjected to Westernization, with a great change in lifestyle, specially in dietary habits, and this may explain the increase in the incidence of diabetes mellitus (DM), metabolic syndrome (MS) and cardiovascular disease among them. Objective: To study the presence of myocardial necrosis and left ventricular hypertrophy (LVH) in a population of Japanese-Brazilians, using the ECG and its relationship with DM and MS. Methods: This was a cross-sectional study which evaluated 1,042 Japanese-Brazilians aged 30 or over, 202 of them born in Japan (Issei) and 840 of them born in Brazil (Nissei), from the second phase of the Japanese-Brazilian Diabetes Study Group initiated in 2000. MS was defined according to the NCEP-ATP III criteria modified for the Japanese. DM and MS were associated with the presence of myocardial necrosis (according to the Minnesota criteria) and LVH (according the Perugia score on the ECG). The statistic chi square method was used to reject the null hypothesis. Results: Of the 1,042 participants, 35.3% had DM (38.6% of the Issei and 34.5% of the Nissei); 51.8% had MS (59.4% of the Issei and 50.0% of the Nissei). The presence of an inactive zone in the diabetic Issei group was not statistically significant when compared to the non-diabetic group, but among the diabetic Nissei group an inactive zone was present in 7.5% of them. There was a statistically significant correlation between MS and LVH in the Issei and Nissei groups. Conclusion: Metabolic disorders presented a high prevalence in Japanese-Brazilians with significant correlations with necrosis and hypertrophy on the ECG.
Fundamento: Al migrar hacia las Américas, los japoneses se sometieron a un proceso de occidentalización, con estilo de vida, y especialmente dieta, muy diferente, lo que puede explicar el aumento de diabetes mellitus (DM), síndrome metabólico (SM) y enfermedades cardiovasculares. Objetivo: Analizar la presencia de necrosis miocárdica e hipertrofia ventricular izquierda (HVI), indicada en ECG, y su relación con DM y SM en población de nipobrasileños. Métodos: Estudio transversal que evaluó a 1.042 nipobrasileños con edad superior a 30 años: 202 nacidos en Japão (iseis) y 840 nacidos en Brasil (niseis), provenientes de la segunda fase del estudio Japanese-Brazilian Diabetes Study Group iniciado en 2000. Se definió el SM desde los criterios de la NCEP-ATP III, modificados para los japoneses. La presencia de DM y SM se asoció a la formación de necrosis miocárdica, según el de Minnesota, y de HVI según el criterio de Perugia, ambas reveladas en el ECG. Se utilizó el método estadístico del Chi-cuadrado para rechazo de la hipótesis de nulidad.Resultados: De los 1.042 participantes, el 35,3% presentaba DM (el 38,6% entre los iseis y el 34,5% en niseis); el 51,8% tenían SM (el 59,4% entre iseis y el 50,0% en niseis). La presencia de zona inactiva en los iseis diabéticos no se mostró estadísticamente significante, si se la compara a los no diabéticos; sin embargo, entre los niseis diabéticos la zona inactiva se presentaba en el 7,5%. Hubo correlación estadísticamente significante entre el SM y la HVE entre iseis y niseis. Conclusión: Disturbios metabólicos tuvieron alta prevalencia en nipobrasileños con correlaciones significantes con necrosis e hipertrofia reveladas por el ECG.
Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Povo Asiático/estatística & dados numéricos , Diabetes Mellitus , Emigrantes e Imigrantes/estatística & dados numéricos , Hipertrofia Ventricular Esquerda/diagnóstico , Síndrome Metabólica , Miocárdio/patologia , Brasil , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etnologia , Eletrocardiografia , Métodos Epidemiológicos , Hipertrofia Ventricular Esquerda/etnologia , Japão/etnologia , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/etnologia , NecroseRESUMO
Early and excessive catecholamine stimulation of the heart increases the overcharge blood pressure and volume on ventricles. Thus worsening myocardial ischemia by causing the death of myocytes. With connective tissue deposition and progressive reduction of heart output. Carvedilol, a b and alpha1-blocker non heart-selective, has been associated to improvement on myocardial function on left ventricle hypertrophy regression. The aim of this study was to evaluate the action of carvedilol in rats undergone to an experimental model of hypertrophic cardiomyopathy by pressure overcharge, through subdiaphragmatic aortic coarctation. Wistar rats (65 animals) divided into four groups: non- coarcted/ treated with placebo, coarcted / treated with placebo, coarcted / treated with 0.1mg kg-1 of carvedilol and coarcted / treated with 1mg/kg of carvedilol. After surgery and 20 days of treatment, the animals were euthanized and samples were collected, fixed in formol 10% and processed using picrossirius staining to quantify connective tissue on left and right ventricles. On those coarcted animals / treated with placebo, there was a rise on the percentage of connective tissue on left and right ventricles; on coarcted animals / treated with 0.1mg kg-1 of carvedilol there was a partial reduction on the amount of collagen tissue of left and right ventricles; and on those coarcted animals / treated with 1mg kg-1 of carvedilol there was a significant reduction on the amount of collagen tissue of left ventricle.
A estimulação catecolaminérgica precoce e excessiva do coração, que ocorre na insuficiência cardíaca congestiva, acentua a sobrecarga de pressão e o volume nos ventrículos, agravando, conseqüentemente, a isquemia miocárdica, causando morte de miócitos com deposição de tecido conjuntivo e progressiva redução do débito cardíaco. O carvedilol, um b e alfa1-bloqueador não cardio-seletivo, vem sendo associado a melhorias na função miocárdica e à regressão da hipertrofia ventricular esquerda. O objetivo do presente trabalho foi avaliar a ação do carvedilol em ratos submetidos a um modelo experimental de hipertrofia miocárdica por sobrecarga de pressão, por meio da coartação da aorta subdiafragmática. Ratos Wistar (65 animais) foram divididos em quatro grupos: não coartados/tratados com placebo, coartados/tratados com placebo, coartados/tratados com 0,1mg kg-1 de carvedilol e coartados/tratados com 1mg kg-1 de carvedilol. Após o procedimento cirúrgico e 20 dias de tratamento, os animais foram submetidos à eutanásia e coletados fragmentos que, depois de fixados em formol a 10% e processados pela técnica histológica convencional utilizando coloração picrossirius, permitiram contagem de tecido conjuntivo nos ventrículos esquerdo e direito. Resultados: nos animais coartados/tratados com placebo, houve aumento na porcentagem de tecido conjuntivo nos ventrículos esquerdo e direito; nos coartados/tratados com 0,1mg kg-1 de carvedilol, houve uma redução parcial da quantidade de tecido colágeno do ventrículo esquerdo e direito, e, nos coartados/tratados com 1mg kg-1 de carvedilol, houve uma redução significativa na quantidade de tecido colágeno do ventrículo esquerdo.
RESUMO
Early and excessive catecholamine stimulation of the heart increases the overcharge blood pressure and volume on ventricles. Thus worsening myocardial ischemia by causing the death of myocytes. With connective tissue deposition and progressive reduction of heart output. Carvedilol, a b and alpha1-blocker non heart-selective, has been associated to improvement on myocardial function on left ventricle hypertrophy regression. The aim of this study was to evaluate the action of carvedilol in rats undergone to an experimental model of hypertrophic cardiomyopathy by pressure overcharge, through subdiaphragmatic aortic coarctation. Wistar rats (65 animals) divided into four groups: non- coarcted/ treated with placebo, coarcted / treated with placebo, coarcted / treated with 0.1mg kg-1 of carvedilol and coarcted / treated with 1mg/kg of carvedilol. After surgery and 20 days of treatment, the animals were euthanized and samples were collected, fixed in formol 10% and processed using picrossirius staining to quantify connective tissue on left and right ventricles. On those coarcted animals / treated with placebo, there was a rise on the percentage of connective tissue on left and right ventricles; on coarcted animals / treated with 0.1mg kg-1 of carvedilol there was a partial reduction on the amount of collagen tissue of left and right ventricles; and on those coarcted animals / treated with 1mg kg-1 of carvedilol there was a significant reduction on the amount of collagen tissue of left ventricle.
A estimulação catecolaminérgica precoce e excessiva do coração, que ocorre na insuficiência cardíaca congestiva, acentua a sobrecarga de pressão e o volume nos ventrículos, agravando, conseqüentemente, a isquemia miocárdica, causando morte de miócitos com deposição de tecido conjuntivo e progressiva redução do débito cardíaco. O carvedilol, um b e alfa1-bloqueador não cardio-seletivo, vem sendo associado a melhorias na função miocárdica e à regressão da hipertrofia ventricular esquerda. O objetivo do presente trabalho foi avaliar a ação do carvedilol em ratos submetidos a um modelo experimental de hipertrofia miocárdica por sobrecarga de pressão, por meio da coartação da aorta subdiafragmática. Ratos Wistar (65 animais) foram divididos em quatro grupos: não coartados/tratados com placebo, coartados/tratados com placebo, coartados/tratados com 0,1mg kg-1 de carvedilol e coartados/tratados com 1mg kg-1 de carvedilol. Após o procedimento cirúrgico e 20 dias de tratamento, os animais foram submetidos à eutanásia e coletados fragmentos que, depois de fixados em formol a 10% e processados pela técnica histológica convencional utilizando coloração picrossirius, permitiram contagem de tecido conjuntivo nos ventrículos esquerdo e direito. Resultados: nos animais coartados/tratados com placebo, houve aumento na porcentagem de tecido conjuntivo nos ventrículos esquerdo e direito; nos coartados/tratados com 0,1mg kg-1 de carvedilol, houve uma redução parcial da quantidade de tecido colágeno do ventrículo esquerdo e direito, e, nos coartados/tratados com 1mg kg-1 de carvedilol, houve uma redução significativa na quantidade de tecido colágeno do ventrículo esquerdo.
RESUMO
Este estudio longitudinal, prospectivo se diseñó para evaluar el efecto del ramipril, un inhibidor de la enzima convertidora de angiotensina (IECA) sobre la masa ventricular, la función diastólica del ventrículo izquierdo (VI) y los valores de tensión arterial en pacientes con hipertensión arterial sistémica esencial (HAS) leve a moderada con hiperinsulinemia. La primera alteración del paciente hipertenso es la disfunción diastólica del VI y el dato de mayor peso como factor predictor de morbimortalidad cardiovascular en la HAS es la hipertrofia ventricular. Existen múltiples estudios que demuestran que no existe una correlación directa entre los valores de tensión arterial y el grado de hipertrofia o disfunción diastólica del ventrículo izquierdo, motivo por el cual se asume la participación de otros factores en la génesis de estas alteraciones funcionales. Por otra parte, está descrito que la insulina posee efectos hipertensores por estimulación simpática, por retener sodio y agua a nivel renal y por estimular la expresión de protooncogenes con el subsecuente desarrollo de fibrosis e hipertrofia miocárdica y vascular. A pesar de que existe en el mercado una gran cantidad de fármacos antihipertensivos, algunos de ellos producen efectos metabólicos adversos, mientras que otros como los inhibidores de la enzima convertidora de angiotensina (IECAS), los ARAII y los bloqueadores del calcio además de controlar los niveles de presión arterial tienen un efecto neutro o benéfico sobre dichos parámetros. Considerando el efecto de los IECAS sobre el perfil metabólico, se realizó un estudio con 24 pacientes hipertensos esenciales con hiperinsulinemia, a los cuales se les realizó evaluación clínica cardiológica y general, electrocardiograma y ecocardiograma en condiciones basales y después de 6 meses de tratamiento con ramipril a dosis de 2.5 a 5 mg/día. Los resultados muestran una reducción significativa de la tensión arterial sistólica (12 mmHg) y diastólica (12 mmHg), de los niveles séricos de insulina basal (23.62 pmol/dL vs 10.42 pmol/dL), y del índice de masa ventricular izquierda (143.8 g/m² vs 118.2 g/m²). En las variables que evalúan la función diastólica del VI no hubo diferencias estadísticamente significativas a excepción de la relación onda E/onda A del flujo transmitral en el grupo de mujeres. Ramipril fue bien tolerado y no se reportaron eventos adversos significativos.
This longitudinal prospective study was designed to assess the effects of the angiotensin converting enzyme inhibitor (ACEI) ramipril on ventricular mass, left ventricle (LV) diastolic function and blood pressure in patients with mild to moderate essential hypertension and hyperinsulinemia. LV diastolic dysfunction is the first target organ alteration occurring in hypertensive patients, while ventricular hypertrophy is the most relevant predictive factor for cardiovascular morbility and mortality in systemic hypertension. Because several studies have demonstrated that there is no direct correlation between blood pressure values and the severity of LV hypertrophy or diastolic dysfunction, it is assumed that other factors are involved in the genesis of these functional alterations. Moreover, the hypertensive effect of insulin is caused by sympathetic stimulation, sodium and water renal retention and protooncogene stimulation leading to myocardial and vascular fibrosis and hypertrophy. We studied 24 hypertensive patients with hyperinsulinemia. All patients underwent an overall and cardiologic clinical evaluation, and electrocardiographic and ecocardiographic studies were performed at baseline and 6 months after being treated with 2.5 to 5 mg/day ramipril. Ramipril treatment significantly reduced systolic (12 mmHg) and diastolic (12 mmHg) pressure levels, basal insulin serum levels (23.62 pmol/dL vs 10.42 pmol/dL), and left ventricle mass index values (143.8 g/m² vs 118.2 g/m²). Among the variables assessing LV diastolic function, only the transmitral flow E/ A wave ratio showed significant differences in women. Ramipril was well tolerated and no significant adverse events were reported. (Arch Cardiol Mex 2003; 73:24-30).