Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension
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.
|Keywords||Aldosterone/blood, Angiotensin II/*antagonists & inhibitors, Biphenyl Compounds/blood/*pharmacology, Body Weight/drug effects, Catecholamines/blood, Double-Blind Method, Electrolytes/metabolism, Hemodynamic Processes/*drug effects, Hypertension/*physiopathology, Receptors, Angiotensin/*antagonists & inhibitors, Tetrazoles/blood/*pharmacology, adult, female, humans, male, middle aged, renin/blood|
Admiraal, P.J.J., Janssen, J.A.M.J.L., Kroodsma, J.M., de Ronde, W.A., Boomsma, F., Sissmann, J., … van den Meiracker, A.H.. (1995). Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension. Hypertension. Retrieved from http://hdl.handle.net/1765/9126