The Vascular Renin System

In the classical endocrine renin—angiotensin system (RAS), renin secreted from the kidney cleaves hepatic angiotensinogen in the circulation to launch a cascade of angiotensin peptides including angiotensin (A) I, II, and III. AII, the most prominent of these peptide hormones, initiates through specific plasma membrane receptors, a host of physiological actions ranging from vasoconstriction to volume and growth regulation (1-4). Circulating plasma levels of renin and/or AII do not always correlate with their purported functions (5, 6),because of inaccuracies of renin and/or AII measurements, or not considering the sodium status (7). Studies with angiotensin-converting enzyme (ACE) inhibitors, and more recently with specific AII receptor antagonists, have demonstrated that even when the circulating levels are low, AII remains a major regulator of many biological responses, including blood pressure (8).