D. Research Implications
At the cellular level the renin-induced increased aldoster-one levels promote myocardial fibrosis and collagen deposition that lead to a stiff ventricle and progressive decrease in normal left ventricular function. Treatment with ACE inhibitors appears to prevent nonmyocyte cellular proliferation and collagen deposition improving myocyte contractile function. Direct aldosterone antago¬nists are being investigated and research is needed in this important area. Direct rennin inhibitors and analogs require further research. Candidate molecules for ther¬apeutic use have thus far been elusive.
ACE inhibitor therapy appears to have a favorable effect on atherosclerosis, which is the major cause of obstruction to the flow of blood through arteries resulting in infarcts that may occur in the heart or the brain (stroke). It appears that angiotensin II causes vasoconstriction and promotes the growth and migration of vascular smooth muscle cells into the media. An increase in smooth muscle cell enzyme causes an increase in free radical production, which promotes the oxidation of low-density lipoprotein (LDL) cholesterol and the progression of the atherosclerotic process. Other favorable effects include an improvement in endogenous fibrinolytic function and vasodilatation produced by bradykinins, prostaglandins, and the power¬ful vasodilator NO (see the chapter Atherosclerosis/ Atheroma).

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