ACE-INHIBITORS AND ATHEROSCLEROSIS

The involvement of the circulating and local renin-angiotensin system in atherosclerotic process has been hypothesized on the basis of experimental data showing presence and specific actions of the components of this system in the vascular wall. In particular, angiotensin II may participate in well known events in atherogenesis as the control of smooth muscle cell growth and proliferation. Recent studies have shown an effect of angiotensin converting enzyme (ACE) inhibition on the development of atherosclerosis in animal models. Captopril and cilazapril prevent myointimal proliferation after vascular injury in rat. Captopril reduces aortic cholesterol content and percentage intimal aortic surface covered by lesions in Watanabe heritable hyperlipidemic rabbits. Captopril also significantly reduces the progression of carotid and coronary lesions in monkeys fed a high cholesterol diet. In addition, a role for converting enzyme inhibitors in reducing aortic and microvascular growth either in hypertensive of normotensive rats has been demonstrated. It is possible that ACE-inhibitors prevent angiotensin II-induced vascular proliferation and thereby suppress the development of atherosclerosis in animals. It is also conceivable that the blood pressure effects of ACE-inhibitors could play a role in the antiatherosclerotic effect shown by these drugs, even though this explanation cannot be addressed by studies dealing with normotensive animals. Then, other mechanisms could be involved, including hypothesized effects of blockade of the renin-angiotensin system on sympathetic nervous system activity, regulation of vascular growth factors and insulin sensitivity. The clinical significance of these experimental findings is unknown. Molecular mechanisms by which the renin-angiotensin system can act on atherosclerosis pathogenesis and the influence of ACE-inhibitors on the course of arterial diseases in humans ought to be important subjects of future investigations.