THE ROLE OF THE EXTRARENAL RENIN-ANGIOTENSIN SYSTEM

A recently recognized role for angiotensin II is that of promoting growth in muscle cells of cardiovascular and renal lineage. This includes vascular smooth muscle cells, mesangial cells, and possibly cardiomyocytes. Pathologic growth of these cells leads to the intimal hyperplasia of atherosclerosis and postangioplasty restenosis, glomerulosclerosis, and left ventricular hypertrophy, respectively. Use of angiotensin-converting enzyme inhibitors has helped to uncover the role of angiotensin II in growth, because these antihypertensive agents have been effective in slowing the development of atherosclerosis and angioplasty restenosis in animal models, the development and progression of glomerulosclerosis in diabetic nephropathy, and the development of left ventricular hypertrophy in pressure overload models in animals and in humans. Understanding specific mechanisms of angiotensin II on the growth process will ultimately 1) elucidate the role of the circulating and tissue renin-angiotensin systems in cardiovascular and renal growth, 2) establish the interaction among vasoconstrictors, growth factors, protooncogenes, and other factors in development of hypertrophy and proliferation, and 3) define a potential therapeutic and preventative approach to cardiovascular and renal diseases in which smooth muscle cell growth plays a critical pathophysiologic role.