Effects of Enalapril on the Vascular Wall in an Experimental Model of Syndrome X

Evidence links the insulin resistance syndrome with endo-thelial dysfunction. Previously, we have described a de-creased endothelial nitric oxide synthase (eNOS) activity in both aortic endothelium and cardiac tissue, and an increased proliferation of aortic primary cultured vascular smooth muscle cells (pC-VSMCs), obtained from fruc-tose-fed rats (FFR), an experimental model of syndrome X. Because the participation of the renin-angiotensin sys-tem (RAS) in this model is still unclear, the present study examined the effect of chronic administration of an angio-tensin converting enzyme (ACE) inhibitor enalapril (E) on pC-VSMCs proliferation and eNOS activity in a conduit artery (aorta) and in resistance vessels (mesenteric vascu-lar bed) from fructose-fed rats. Male Wistar rats were used: Control, FFR, Control E, and FFR E (n 8 in each group). After 8 weeks, tissue samples were obtained and 10 % fetal calf serum (FCS) proliferative effect was examined in pC-SMCs of aortic and mesenteric arteries by [3H]thymidine incorporation. The eNOS activity was es-timated in endothelial lining from both origins by conver-sion of [3H]arginine into [3H]citrulline. The FFR aortic and mesenteric pC-VSMCs showed a significantly in-creased 10 % FCS-induced [3H]thymidine incorporation compared to controls. The FFR aortic and mesenteric endothelium eNOS activity was significantly decreased. Chronic treatment with E abolished the increased prolif-eration and restored eNOS activity. These data confirm that changes in VSMCs proliferation and endothelial dys-function at different levels of the vascular system are involved in syndrome X, and that the inhibition of angio-tensin II production can revert those changes, suggesting an important role for RAS and possibly kinins, in the physiopathologic mechanism of this model of syndrom