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 AT(1 )-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 bl ood pressure remained unchanged throughout the study. Three hours afte r its administration and before LBNP, losartan selectively increased r enal blood flow (PAH clearance) by 8.3% (3.5 to 13.1%, 95% CI) from 1. 25 +/- 0.08 1 min(-1) (P < 0.05) and decreased plasma aldosterone leve ls 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 decr ease in central venous pressure and increases in forearm (plethysmogra phy) and splanchnic (indocyanine green clearance) vascular resistances which were similar after losartan and placebo administrations. Losart an blunted the LBNP-induced increase in renal vascular resistance obse rved at -20 mm Hg after placebo but a similar increase in glomerular f iltration rate (inulin clearance) was observed at LBNP -10 and -20 mm Hg after losartan and placebo. Calculated filtration fraction increase d after placebo (LBNP -10 mm Hg) and losartan (LBNP -20 mm Hg). Finall y, LBNP-induced changes in biological parameters were similar after lo sartan and placebo at all levels of LBNP. 4 Thus, losartan does not in terfere with the adaptive forearm and splanchnic vascular responses an d preserves renal haemodynamics during orthostatic stress simulated by LBNP in healthy volunteers.