Is angiotensin II a growth factor masquerading as a vasopressor?

The actions of angiotensin II can be described in terms of the three paradigms listed in Table 1. According to the first paradigm (organ physiology), angiotensin II is a pressor, while the second (cell biochemistry) views it as an extracellular messenger that, by promoting Ca2+ release within cells, causes vasoconstriction and a weak positive inotropic response by the heart. However, neither of these paradigms fully explains the remarkable ability of angiotensin converting enzyme inhibitors to improve the prognosis for patients with heart failure. To account for these clinical effects of angiotensin converting enzyme inhibitors, we will probably need to invoke the third paradigm (gene expression), which views angiotensin II as a growth factor that promotes and modifies protein synthesis. Angiotensin II, therefore, should probably not be viewed simply as a vasoconstrictor with a side effect to promote hypertrophy, but instead as a growth factor that, because it utilizes Ca2+ to mediate its effects on gene expression, also increases smooth muscle tone and myocardial contractility. This view of angiotensin II as a growth factor helps us to understand the clinical benefit of angiotensin converting enzyme inhibitors as arising from inhibition of maladaptive changes in the failing heart (gene expression) as well as from the reduced afterload (organ physiology) that results from decreased smooth muscle tone (cell biochemistry).