ROLE OF ANGIOTENSIN IN PRESSURE OVERLOAD-INDUCED HYPERTROPHY IN RATS - EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS, AN AT(1) RECEPTOR ANTAGONIST, AND SURGICAL REVERSAL

The renin-angiotensin system (RAS) has been proposed to play a major r ole in causing the heart to hypertrophy during pressure overload. We e xamined whether blockade of this system by the angiotensin-converting enzyme (ACE) inhibitors enalapril (0.5 or 20 mg/kg p.o.) or ramipril(1 .0 mg/kg p.o.) or the angiotensin receptor (AT(1)) antagonist losartan (3.0 mg/kg p.o.) could prevent pressure overload-induced hypertrophy. Pressure overload was produced by abdominal aortic constriction in ra ts. Cardiac hypertrophy was assessed by an increase in the ratio of le ft ventricular (LV) weight to body weight and total protein content of the left ventricle. Treatment with enalapril or ramipril, initiated 3 weeks after aortic banding and continued for 3 more weeks, failed to prevent the progression or cause regression of cardiac hypertrophy. Tr eatment for 6 weeks with ramipril initiated immediately after aortic b anding also failed to prevent cardiac hypertrophy. Losartan treatment initiated 3 weeks after aortic banding and continued for 3 more weeks resulted in a slight but significant reduction in the extent of cardia c hypertrophy (45.6% hypertrophy in controls and 35.6% hypertrophy in losartan-treated animals, p < 0.05, n = 11 and 10, respectively). Surg ical removal of bands 3 weeks after placement reduced cardiac hypertro phy to a greater extent than that observed in losartan-treated animals . These results suggest that angiotensin may not play a major role in causing pressure overload-induced hypertrophy or in maintaining such h ypertrophy.