Hemodynamic and biochemical effects of AT1-receptor antagonist irbesartan in essential hypertension

The effects of the novel AT1-receptor antagonist irbesartan (SR 47436 or BMS 186295) on 24-h ambulatory blood pressure (ABP), renin, angiotensin I and II, aldosterone, norepinephrine and urinary excretion of uric acid were studied in 86 sodium-unrestricted hypertensive patients. According to a double-blind parallel group trial patients were randomized for one week to a once-daily oral dose of irbesartan (1, 25 or 100 mg) or placebo after a placebo run-in period of 3 weeks. Compared to placebo 24-h ABP did nor change with the 1 mg dose, whereas it fell (systolic/diastolic, mean and 95% Cl) by 7.0 (4.2–9.8)/6.1 (3.9–8.1) with the 25 mg and by 12.1 (8.1–14.1)/7.3(5.1–8.2) mmHg with the 100 mg dose. Heart rate did not change with either dose. With the 25 mg dose the antihypertensive effect was attenuated during the second half of the recording, whereas with the 100 mg dose it was maintained for 24 h. Baseline renin and the antihypertensive response to the 25 and 100 mg dose were correlated (r=0.68, p>0.01). Renin did not change with the 1 mg dose, whereas it rose 3 to 4-fold with the 25 mg and 4 to 5-fold with the 100 mg dose. With the 100 mg dose renin was still 2-fold elevated, 24 h after administration. The AT1-receptor antagonist-induced changes in renin were associated with parallel increments in angiotensin I and II. Aldosterone, despite AT1-receptor blockade did not fall. Compared to baseline, plasma norepinephrine moderately increased with the 100 mg dose. Serum uric acid and its 24-h urinary excretion did not change. In conclusion, in essential hypertension, irbesartan effectively lowers blood pressure. This effect is maintained for 24 h with 100 mmHg dose. Unlike losartan, irbesartan exerts no uricosuric effect, suggesting that this is an effect unrelated to AT1-receptor blockade