Investigation of antihypertensiv? and renoprotectiv? potential of natural and synthetic compounds in the experimental models of cardiovascular and renal diseases

It is one of the objectives of the proposed studies to examine the effect of some naturally occuring antioxidants on the progression of cardiovascular and renal diseases. First, we propose to examine the effects of an extract of olive leaves, that contains powerful antioxidant, in animal models of essential hypertension and renal failure. Also, we propose to examine the role of advanced glycation end products (AGEs) which by forming collagen cross-links exert adverse cardovascular and renal effects. We propose to examine the effects of alagebrium, a collagen cross-links breaker, on the pathogenesis of spontaneous hypertension in rats and on the development of renal insufficiency. Next, we plan to study the beneficial effects of resveratrol, a powerful antioxidant isolated from grapes. This study will involve rats with spontaneous hypertension as well as rats with experimental malignant hypertension. Finally, we plan to examine the role of interplay between renin-angiotensin system and oxidative stress in mediating acute postischemic renal failure. We will study the progression of renal failure induced by an ischemic episode in hypertensive rats given either placebo, angiotensin II, type 1 and 2, receptor blockers, an antioxidant, or combination of angiotensin II receptor blockers and antioxidant. The results should delineate the roles of the renin-angiotensin system and oxidative stress in the pathogenesis of acute renal failure in hypertensive subjects.