Cardiac Hypertrophy and the Blockade of Angiotensin II Receptors by Losartan in Salt-Loaded Dahl Salt-Sensitive Rats.

Abstract

We studied the effects of direct blockade of angiotensin II by a non-peptide angiotensin II receptor (AT1) antagonist, losartan, on development of cardiovascular hypertrophy in salt-loaded Dahl salt-sensitive (DS) rats. Six-week-old male DS rats were fed a 4% NaCl diet and were simultaneously treated with one of two doses of oral losartan for 7 weeks. Vehicle-treated rats were given tap water alone. Blood pressure and body weight were monitored. The low-dose of losartan (30 mg/kg/day; n=12) blunted the rise in tail-cuff systolic blood pressure only transiently and did not reduce the left ventricular mass (ratio of left ventricular weight/body weight), when compared to the vehicle control (n=12). The high dose of losartan (100mg/kg/day; n=6) blunted the rise in blood pressure; however, left ventricular mass was not significantly lower in rats given the high dose of losartan than in those given vehicle (n= 12). The pressor response to intravenous angiotensin II was greatly suppressed in salt-loaded DS rats treated with 30mg/kg/day of losartan. These results suggest that losartan has minor hypotensive effects without reducing cardiovascular hypertrophy in DS rats fed a 4 % NaCl diet. We conclude that angiotensin II blockade has only minor effects on hypertension and cardiovascular hypertrophy in salt- loaded DS rats, and that the renin-angiotensin system may play no major role in the development of cardiovascular hypertrophy in DS rats on a moderately high-salt diet. (Hypertens Res 1994; 17: 199-203)