(Hypertension. 1995;25:22-29.)
© 1995 American Heart Association, Inc.
Articles |
Hemodynamic and Biochemical Effects of the AT1 Receptor Antagonist Irbesartan in Hypertension
From the Department of Internal Medicine I, University Hopital Dijkzigt, Rotterdam (A.H. van den M., P.J.J.A., J.A.J., F.B., A.J.M.V., M.A.D.H.S.); U-Gene Research BV, Utrecht (J.-M.K., W.A.M. de R.), the Netherlands; Sanofi Recherche, Montpellier, France (J.S.); the Department of Nephrology, University Hospital Utrecht (P.J.B.); and the Department of Epidemiology and Biostatistics, Erasmus University Rotterdam (P.G.M.M.).
Abstract We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and with the 100-mg dose, it was maintained for 24 hours. Baseline values of renin and the antihypertensive response to the 25- and 100-mg doses were well correlated (r=.68, P<.01). Renin did not change with the 1-mg dose, but it rose threefold to fourfold with the 25-mg dose and fourfold to fivefold with the 100-mg dose 4 to 6 hours after administration. With the 100-mg dose, renin was still elevated twofold 24 hours after dosing. The changes in renin induced by the AT1 receptor antagonist were associated with parallel increments in angiotensin I and angiotensin II. Aldosterone, despite AT1 receptor blockade, did not fall. Compared with baseline values, plasma norepinephrine increased moderately with the 100-mg but not with 25- or 1-mg dose. Serum uric acid and its 24-hour urinary excretion did not change. In conclusion, in essential hypertension, once-daily irbesartan effectively lowers blood pressure. This effect is maintained for 24 hours with a 100-mg dose. Unlike the AT1 receptor antagonist losartan, irbesartan exerts no uricosuric effect, suggesting that this is an effect unrelated to AT1 receptor blockade.
Key Words: receptors, angiotensin • hypertension, essential • hemodynamics • renin • angiotensin I • angiotensin II • aldosterone • norepinephrine • uric acid
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