Chronic administration of losartan reverses cardiovascular changes in hypertensive fructose-fed rats.

The cluster of risk factors including hyperinsulinemia, insulin resistance, hypertriglyceridemia and hypertension has been called syndrome X. Several evidences link the insulin resistance syndrome with endothelial dysfunction. Since the participation of the renin-angiotensin system (RAS) in this pathology is still unclear, the present study examined the effect of chronic administration of an angiotensin AT1 receptor antagonist, losartan (L), on endothelial nitric oxide synthase (eNOS) activity in aortic endothelium and cardiac tissue, and on the proliferation of primary cultured aortic smooth muscle cells (SMC), obtained from fructose-fed rats (FFR), an experimental model of syndrome X Male Wistar rats were used: Control, FFR and FFR+L (n = 8 in each group). After 8 weeks, tissue samples were obtained and 10% fetal calf serum (FCS) proliferative effect was examined in SMC by 3H-thymidine incorporation and cell counting. The eNOS activity was estimated in aortic endothelial lining and cardiac homogenates by conversion of 3H-arginine into 3H-citrulline. FFR aortic SMC showed a significantly increased 10% FCS-induced 3H-thymidine incorporation and cell number compared to controls. FFR aortic and cardiac eNOS activities were significantly decreased. Chronic treatment with L decreased systolic blood pressure,reverted cardiac hypertrophy, abolished the increased SMC proliferation and restoredeNOS activity. These data confirm that changes in SMC proliferation and endothelial dysfunction at different levels of the cardiovascular system are involved in syndrome "X", and that AT1 receptor blocking can revert those changes, suggesting an important role of the RAS, possibly mediated by AT2 receptors and kinins, in the physiopathological mechanisms of this model.

Síndrome X / X Syndrome

A Síndrome X foi primeiramente descrita por Kemp, em 1973, sendo caracterizada por um grupo de pacientes que apresentavam dor precordial típica e estudo angiográfico das artérias coronárias normal. Cerca de 20 por cento dos pacientes que säo submetidos ao cateterismo cardíaco para investigaçäo de angina pectoris apresentam artérias normais. Várias teorias têm sido descritas com o objetivo de determinar o mecanismo fisiopatológico desencadeante da dor, incluindo espasmo coronariano, anormalidades metabólicas, diminuída reserva de fluxo coronariano, percepçäo alterada da dor, disfunçäo endotelial e até mesmo fatores psicossomáticos. Os últimos estudos realizados utilizando o ultrassom intra-coronariano desmistificaram a idéia de artérias normais já que eles evidenciam a presença de espessamento das paredes e placas ateromatosas näo perceptíveis pelos estudos angiográficos habituais