Effects of the angiotensin type I receptor antagonist, losartan, on systemic and regional vascular responses to lower body negative pressure in healthy volunteers.
1. The effects of a single oral dose (50 mg) of the angiotensin II AT1-receptor antagonist, losartan, on the systemic and regional vascular responses to simulated orthostatic stress by the lower body negative pressure (LBNP) technique were investigated in nine healthy volunteers, in a double-blind, placebo-controlled crossover study. 2. Arterial blood pressure remained unchanged throughout the study. Three hours after its administration and before LBNP, losartan selectively increased renal blood flow (PAH clearance) by 8.3% (3.5 to 13.1%, 95% CI) from 1.25 +/- 0.08 l min-1 (P < 0.05) and decreased plasma aldosterone levels by 58% (29 to 87%, 95% CI) from 22 +/- 3 ng 100 ml-1 (P < 0.05). 3. LBNP at -10 and -20 mm Hg induced a progressive and significant decrease in central venous pressure and increases in forearm (plethysmography) and splanchnic (indocyanine green clearance) vascular resistances which were similar after losartan and placebo administrations. Losartan blunted the LBNP-induced increase in renal vascular resistance observed at -20 mm Hg after placebo but a similar increase in glomerular filtration rate (inulin clearance) was observed at LBNP -10 and -20 mm Hg after losartan and placebo. Calculated filtration fraction increased after placebo (LBNP -10 mm Hg) and losartan (LBNP -20 mm Hg). Finally, LBNP-induced changes in biological parameters were similar after losartan and placebo at all levels of LBNP. 4. Thus, losartan does not interfere with the adaptive forearm and splanchnic vascular responses and preserves renal haemodynamics during orthostatic stress simulated by LBNP in healthy volunteers.
Duranteau
J
J
Services d'Anesthésiologie, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.
Pussard
E
E
Berdeaux
A
A
Giudicelli
J F
JF
D000328:Adult; D057911:Angiotensin Receptor Antagonists; D017704:Baroreflex / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004311:Double-Blind Method; D005542:Forearm / Q000098:blood supply*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008150:Lower Body Negative Pressure; D008297:Male; D012079:Renal Circulation / Q000187:drug effects*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D019808:Losartan