AT(1) RECEPTOR ANTAGONIST, TCV-116, DOES NOT PREVENT CARDIAC-HYPERTROPHY IN SALT-LOADED DAHL SALT-SENSITIVE RATS

1. We investigated the effects of direct blockade of angiotensin II (A ngII) by a potent, non-peptide angiotensin II type 1 (AT(1)) receptor antagonist, TCV 116, on the development of cardiac hypertrophy in salt -loaded Dahl salt-sensitive rats. 2. Six week old male Dahl salt-sensi tive rats (n = 44) were fed a 4% salt diet and were simultaneously giv en various doses of TCV 116 orally for 7 weeks. Each control group rec eived vehicle alone. 3. Dietary high salt intake elevated blood pressu re continuously and caused left ventricular hypertrophy in rats treate d with vehicle. TCV 116 had a minor effect on the rise in blood pressu re. Left ventricular mass (left ventricular weight/body-weight) decrea sed slightly but not significantly, in rats treated with 3 mg/kg per d ay of TCV 116 (n = 8), Higher doses of TCV 116 (6 and 10 mg/kg per day ; n = 8 each) did not show a decrease in left ventricular mass compare d with the vehicle control. 4. These results suggest that AngII blocka de has only minor effects on hypertension and on cardiac hypertrophy i n salt-loaded Dahl salt-sensitive rats and that the renin-angiotensin system may not contribute to the development of cardiac hypertrophy in Dahl salt-sensitive rats on a moderately high-salt diet.