COMPARISON BETWEEN CHRONIC CONVERTING-ENZYME INHIBITION AND AT(1) BLOCKADE IN MREN2 TRANSGENIC RATS

We compared the consequences of chronic angiotensin-converting enzyme (ACE) inhibition with quinapril and of specific AT(1) blockade with lo sartan in a renin-dependent model of hypertension, the (mRen2)27 trans genic rats (TG). Animals were orally treated with 10 mg/kg/24 h of eit her quinapril (TGQ, n = 13) or losartan (TGL, n = 12) from age 4 to ag e 9 weeks. Indirect systolic blood pressure (SEP), and sodium and wate r balances were measured for 3 consecutive weeks. Nine-week-old rats w ere instrumented to record aortic BP in the conscious state. In additi on, they received an infusion of glucose and saline to increase their diuresis and thus allow accurate assessment of their renal excretion d uring short time periods. These rats were studied for three one-h peri ods: (a) baseline, (b) after the administration of a bradykinin (BK) a ntagonist, and (c) after a cross-treatment; i.e., TGQ rats receiving l osartan (10 mg/kg intravenously, i.v.) and TGL rats receiving quinapri l (10 mg/kg i.v.). TGL rats differed from TGQ rats by an un consistent ly lower indirect SEP associated with significantly lower urinary volu me and sodium excretion, whereas the sodium balance did not differ bet ween the two groups. In conditions of fixed sodium intake the aortic B P of TGQ rats was still nonsignificantly different from that of TGL ra ts, and TGQ rats also exhibited twofold higher natriuresis. The BK ant agonist had no effect in either group, whereas losartan decreased the BP of TGQ rats. We conclude that in TG rats ACE inhibition is associat ed with an increased natriuresis as compared with specific AT(1) block ade, an effect that is independent of the sodium intake. Because a BK antagonist had no effect, such a difference might be due to an antinat riuretic effect of AT(2) receptors in chronic conditions.