ROLE OF THE RENIN-ANGIOTENSIN SYSTEM IN SYSTEMIC AND REGIONAL VASCULAR-RESPONSES TO ORTHOSTATIC STRESS IN HEALTHY-VOLUNTEERS

The effects of a single oral dose (5 mg) of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, on the systemic and regional vascul ar responses to simulated orthostatic stress by the lower body negativ e pressure (LBNP) technique were investigated in eight healthy volunte ers, in a double-blind, placebo-controlled crossover study. Arterial b lood pressure remained unchanged throughout the study. Ramipril increa sed significantly forearm (venous occlusion plethysmography, + 37% +/- 4% from 1.98 ml . min(-1). 100 ml(-1)) and renal (PAH clearance, + 6 +/- 2% from 1.20 1 . min(-1)) blood flows and decreased corresponding vascular resistances, 150 minutes after its administration and before LBNP. It also significantly reduced calculated filtration fraction and inhibited by approximately 86% plasma ACE activity. Lower body negati ve pressure at -10 and -20 mmHg induced a progressive and significant decrease in central venous pressure and significant increases in forea rm, splanchnic (indocyanine green clearance) and total peripheral vasc ular resistances which were of the same magnitude after ramipril and p lacebo administrations. Ramipril blunted the LBNP-induced increase in renal vascular resistance observed at -20 mmHg after placebo but a sim ilar increase in glomerular filtration rate (inulin clearance) was obs erved at LBNP-10 and -20 mmHg after ramipril and placebo. Calculated f iltration fraction increased after placebo (LBNP-10 mmHg) and ramipril (LBNP-20 mmHg). Finally, LBNP-induced changes in biological parameter s were similar after ramipril and placebo at all levels of LBNP. Thus, ramipril does not interfere with the adaptive forearm and splanchnic vascular responses and preserves renal hemodynamics during orthostatic stress simulated by LBNP in healthy volunteers.