Comparison Between Chronic Converting Enzyme Inhibition and AT1 Blockade in mRen2 Transgenic Rats

Abstract

We compared the consequences of chronic angiotensin-converting enzyme (ACE) inhibition with quinapril and of specific AT1 blockade with losartan in a renin-dependent model of hypertension, the (mRen2)27 transgenic rats (TG). Animals were orally treated with 10 mg/kg/24 h of either quinapril (TGQ, n = 13) or losartan (TGL, n = 12) from age 4 to age 9 weeks. Indirect systolic blood pressure (SBP), and sodium and water balances were measured for 3 consecutive weeks. Nine-week-old rats were instrumented to record aortic BP in the conscious state. In addition, they received an infusion of glucose and saline to increase their diuresis and thus allow accurate assessment of their renal excretion during short time periods. These rats were studied for three one-h periods: (a) baseline, (b) after the administration of a bradykinin (BK) antagonist, and (c) after a cross-treatment; i.e., TGQ rats receiving losartan (10 mg/kg intravenously, i.v.) and TGL rats receiving quinapril (10 mg/kg i.v.). TGL rats differed from TGQ rats by an unconsistently lower indirect SBP associated with significantly lower urinary volume and sodium excretion, whereas the sodium balance did not differ between the two groups. In conditions of fixed sodium intake the aortic BP of TGQ rats was still nonsignificantly different from that of TGL rats, and TGQ rats also exhibited two-fold higher natriuresis. The BK antagonist had no effect in either group, whereas losartan decreased the BP of TGQ rats. We conclude that in TG rats ACE inhibition is associated with an increased natriuresis as compared with specific AT1 blockade, an effect that is independent of the sodium intake. Because a BK antagonist had no effect, such a difference might be due to an antinatriuretic effect of AT2 receptors in chronic conditions.