Background: Endothelin contributes to the maintenance of vascular tonus in both the systemic circulation and in regional vascular beds. The purpose of the study was to measure the effect of the endothelin A antagonist BQ-123 on renal hemodynamics, tubular function, vasoactive hormones, and blood pressure (BP) in healthy men.
Methods: In a randomized, placebo-controlled, double-blind dose-response study of 11 healthy men we measured the effect of BQ-123 on glomerular filtrations rate (GFR), renal plasma flow (RPF), fractional excretion of sodium (FENa), lithium clearance (CLi), BP, and plasma concentrations of renin (PRC), angiotensin II (Ang II), atrial and brain natriuretic peptides (ANP, BNP), and vasopressin (AVP). BQ-123 was infused intravenously at the rate of 0.1, 0.2, and 0.3 mg/kg for 1 h, and the effects were measured before, during, and after infusion.
Results: The GFR and RPF were not significantly changed by BQ-123. The FENa was increased (20%, medium dose), and CLi was unchanged. Systolic BP remained constant, whereas diastolic BP decreased (-6.3%, medium dose), and pulse rate increased (7.1%, medium dose). BQ-123 increased both PRC (62%, medium dose) and Ang II (70%, medium dose). The changes in FENa, diastolic BP, pulse rate, and Ang II gradually increased up to medium dose, and in PRC up to high dose. The ANP, BNP, and AVP were practically unchanged by BQ-123.
Conclusions: Infusion of an endothelin A antagonist resulted in an increase in renal sodium excretion despite a stimulation of the renin-angiotensin system and a decrease in diastolic BP.