ANGIOTENSIN-II MAINTAINS, BUT DOES NOT MEDIATE, ISOPROTERENOL-INDUCEDCARDIAC-HYPERTROPHY IN RATS

The role of angiotensin II (ANG II) in the development of isoprotereno l (Iso)-induced cardiac hypertrophy was examined in rats. Iso increase d cardiac mass, left ventricular RNA-to-DNA ratio, and the cardiac con tent of both myosin heavy chain and hydroxyproline in a dose-dependent manner, indicating that Iso-induced cardiac hypertrophy involves grow th of both muscle and connective tissue. Cardiac hypertrophy reverted within 11-14 days after cessation of Iso. Propranolol prevented develo pment of Iso-induced cardiac hypertrophy but did not affect the rate o f its reversal. The ANG IT receptor blocker losartan (Los) did not sig nificantly decrease the hypertrophic response to Iso. Los injected aft er cessation of Iso dramatically enhanced the reversal of cardiac hype rtrophy, even in rats that received Los with Iso during the induction of Iso-induced cardiac hypertrophy. ANG II, injected continuously at a subpressor dose that did not affect heart weight when given alone, in hibited reversal of cardiac hypertrophy when given after cessation of Iso. Los did not significantly affect the induction of the protooncoge ne c-fos by Iso. We conclude that endogenous ANG II has a major functi on in maintaining Iso-induced cardiac hypertrophy but does not mediate its induction. This suggests that different interactive stimuli may b e required for development of cardiac hypertrophy, i.e., for initiatio n and for maintenance.