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.
Miatello
R
R
Dept. of Pathology, School of Medicine, National University of Cuyo, Av. Libertador 80, Centro Universitario 5500, Mendoza, Argentina. rmiatell@fcm.uncu.edu.ar
Risler
N
N
Castro
C
C
Cruzado
M
M
González
S
S
Zumino
A Ponce
AP
D000804:Angiotensin II / Q000378:metabolism; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004727:Endothelium / Q000378:metabolism; D005632:Fructose / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D017566:Microvascular Angina / Q000188:drug therapy* / Q000209:etiology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects; D051381:Rats; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects
D057912:Angiotensin II Type 2 Receptor Blockers; D000959:Antihypertensive Agents; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D005632:Fructose; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019808:Losartan