TY - JOUR
T1 - Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension
AU - Van Den Meiracker, Anton H.
AU - Admiraal, Peter J.J.
AU - Janssen, Joop A.
AU - Kroodsma, Jan Maarten
AU - De Ronde, Wijnand A.M.
AU - Boomsma, Frans
AU - Sissmann, Joëlle
AU - Blankestijn, P. J.
AU - Mulder, Paul G.M.
AU - Man In 't Veld, Arie J.
AU - Schalekamp, Maarten A.D.H.
PY - 1995/1/1
Y1 - 1995/1/1
N2 - 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 meditation 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.
AB - 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 meditation 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.
KW - aldosterone
KW - angiotensin I
KW - angiotensin II
KW - hemodynamics
KW - hypertension, essential
KW - norepinephrine
KW - receptors, angiotensin
KW - renin
KW - uric acid
UR - http://www.scopus.com/inward/record.url?scp=0028963378&partnerID=8YFLogxK
M3 - Article
C2 - 7843749
AN - SCOPUS:0028963378
SN - 0194-911X
VL - 25
SP - 22
EP - 29
JO - Hypertension
JF - Hypertension
IS - 1
ER -