Angiotensin II, angiotensin-converting enzyme inhibitors, and blood vessel structure

Angiotensin-converting enzyme (ACE) inhibitors are effective hypotensive agents in hypertension of different types and degree. Probably, they lower pressure by reducing angiotensin II (AII); the varied timing of their hypotensive effect suggests that AII increases blood pressure in more than one way. Infusion studies show two effects of AII: at moderate dose, a rapid vasoconstrictor action; at lower dose, a slow-developing but ultimately large hypertensive effect. Vascular hypertrophy develops during the slow pressor response; at least part of the hypertrophy results from a nonpressor mechanism. In vitro studies show that AII has mitogenic and trophic actions on vascular smooth muscle cells in culture and that it stimulates synthesis of extracellular matrix proteins. One of these actions may produce the nonpressor component of vascular hypertrophy. ACE inhibitors lower pressure in the spontaneously hypertensive rat (SHR) and when given in young animals produce a hypotensive effect that endures long after the period of treatment. An action of endogenous AII, possibly a paracrine effect within the vessel wall, may cause vascular hypertrophy in young SHR with long-lasting effects on arterial pressure.