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Effects of drugs that activate the nitric oxide-GMPc pathway on the vascular alterations associated with renovascular hypertension


Hypertension is a major health problem. The two kidney, one clip model of hypertension elicits significant activation of the renin angiotensin system and promotes vascular remodeling associated with oxidative stress and activation of matrix metalloproteinases (MMPs). These enzymes are regulated by oxidative stress. Statins (cholesterol lowering drugs) and sildenafil (a phosphodiesterase 5 inhibitor used in erectile dysfunction) exert pleiotropic effects including improved endothelial function and reduction of blood pressure, which may result of activation of the NO-cGMP pathway. Since the expression/activity of MMPs may be affected by oxidative stress and both statins and sildenafil have antioxidant effects, it is possible that these drugs prevent the vascular remodeling during 2K-1C hypertension. We will examine biochemical and molecular involved in these possible effects. (AU)

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