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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Internal Medicine I, University Hospital Dijkzigt, Rotterdam, The Netherlands.
A H
AH
van den Meiracker
P J
PJ
Admiraal
J A
JA
Janssen
J M
JM
Kroodsma
W A
WA
de Ronde
F
F
Boomsma
J
J
Sissmann
P J
PJ
Blankestijn
P G
PG
Mulder
A J
AJ
Man In 't Veld
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000097:blood / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004311:Double-Blind Method; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000097:blood / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D002395:Catecholamines; D004573:Electrolytes; D013777:Tetrazoles; D000804:Angiotensin II; D000450:Aldosterone; D012083:Renin; D000077405:Irbesartan