The Renin–Angiotensin– Aldosterone System and Other Vasoactive Substances

The renin–angiotensin system is important for the regulation of vascular smooth muscle tone, fluid and electrolyte balance, and the growth of cardiac and vascular smooth muscle. A normally functioning renin– angiotensin system contributes to the routine control of arterial blood pressure. A variety of basic and clinical investigations have resulted in a broader understanding of the role of the renin–angiotensin system in the cardiovascular pathophysiology of hypertension, congestive heart failure, and more recently, atherosclerosis. Whether or not abnormal activity of the renin– angiotensin system contributes to the primary etiology of these diseases, pharmacological inhibition of the renin–angiotensin system has proved to be a valuable therapeutic strategy in the treatment of hypertension and congestive heart failure. The classical renin–angiotensin system comprises a series of biochemical steps (Fig. 18.1) leading to the production of a family of structurally related peptides (e.g., angiotensin II, angiotensin III, and other smaller peptides with bioactivity). Sites for pharmacological intervention in this system include the enzymatic steps catalyzed by renin, angiotensin-converting enzyme (ACE), and angiotensin receptors that mediate a particular physiological response.