Short-term and sustained renal effects of angiotensin II receptor blockade in healthy subjects.
We investigated the short-term and sustained hormonal and renal effects of angiotensin II (Ang II) receptor blockade in normotensive healthy volunteers. Twenty-four subjects maintained on a fixed sodium diet were randomized to receive for 8 days a placebo or 10 or 50 mg doses of the Ang II antagonist irbesartan (SR 47436, BMS 186295) according to a double-blind, parallel group design. Plasma renin activity, plasma immunoreactive Ang II and aldosterone levels, blood pressure, renal hemodynamics, and urinary electrolyte excretion were measured for 8 hours after the first and eighth administration of each dose of irbesartan or placebo. Ang II receptor blockade with irbesartan induced a dose-dependent compensatory increase in plasma renin activity and plasma angiotensin levels and a significant decrease in plasma aldosterone levels. The compensatory rise in plasma renin activity and Ang II levels was more pronounced on day 8, reflecting a long duration of the blocking effect of irbesartan. Irbesartan induced small changes in blood pressure and did not significantly modify renal blood flow and glomerular filtration rate. However, a significant decrease in filtration fraction was observed during receptor blockade on days 1 and 8. The tubular effects of irbesartan were characterized by a dose-dependent increase in sodium and chloride excretions. Interestingly, the cumulative natriuretic response to Ang II receptor blockade was similar on days 1 and 8, suggesting that in these subjects, renal Ang II receptors are not blocked over 24 hours during repeated administration even though this antagonist has a long duration of action (t1/2 of 15 to 17 hours).(ABSTRACT TRUNCATED AT 250 WORDS)
Burnier
M
M
Division of Hypertension, CHUV, Lausanne, Switzerland.
Hagman
M
M
Nussberger
J
J
Biollaz
J
J
Armagnac
C
C
Brouard
R
R
Weber
B
B
Brunner
H R
HR
D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004039:Diet, Sodium-Restricted; D004311:Double-Blind Method; D004573:Electrolytes / Q000652:urine; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007444:Inulin / Q000097:blood / Q000652:urine; D000077405:Irbesartan; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011945:Receptors, Angiotensin / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004573:Electrolytes; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D007444:Inulin; D000077405:Irbesartan