Mediating the cardiovascular and renal effects of hyperhomocysteinemia in rats: Role of angiotensin П type I receptor

Abstract

Hyperhomocysteinemia is usually associated with cardiovascular and renal disorders. Hyperhomocysteinemia is proved to be a cause of cell cytotoxicity, lipid peroxidation, platelet aggregation, increased activation of the coagulation system and stimulation of vascular smooth muscle cell proliferation. Aim: To identify whether the pathological changes on cardiovascular and renal systems induced by hyperhomocysteinemia could be mediated through the activation of angiotensin II type 1 receptors (AT1R) in rats. Methods: Animals were randomized into 3 groups. Each group contained 5 rats. Hyperhomocysteinemia was induced by methionine delivered in drinking water in a concentration of 1.5 g/kg/day per rat based on average water intake for 12 weeks in group II and group III. Valsartan was administered orally in drinking water at a concentration to deliver 30 mg/kg/day per rat in group III. Withdrawal of blood samples for chemical and spectral assay of antioxidant markers was done .Animals were sacrificed, heart, kidney and blood vessels were processed for histopathology . Results: There was a significant improvement in the serum levels of blood urea nitrogen in methionine-valsartan-treated group (GIII) rather than methionine-induction group (GII). In addition, there was marked improvement in methionine-valsartan treated group (GIII) than in methionine-induction group (GII) regarding interstitial edema, focal degeneration of myocytes and congestion. When comparing vacuolar degeneration of the medial layer, focal endothelial injury and wall thickness, we found marked improvement in methionine-valsartan-treated group (GIII) than in methionine-induction group (GII). Conclusion: Blocking Ang II AT1- receptors by valsartan reduces cardiovascular and renal changes in rats with hyperhomocysteinemia.