Dose- and time-dependency of the dilator effects of the endothelin antagonist, BQ-123, in the human forearm

Aims Endothelin-1 is a potent endogenous vasoconstrictor that acts on the endothelin A (ETA) receptor. The dose-response and time-course of the dilator effect of the ETA receptor antagonist, BQ-123, was investigated in the forearm of healthy volunteers. Methods Forearm blood flow was measured using mercury-in rubber strain gauge venous occlusion plethysmography. Results Following intra-arterial infusion of BQ-123 (50 nmol min(-1)) for 5 min, forearm blood flow increased by approximately 60% over the next 60 minutes; lower doses were without significant effect. The degree of dilatation was similar to that observed in previous studies using 20-fold larger doses. Conclusions This study confirms that basal endothelin-1 has a role in the physiological regulation of vascular tone. It is possible that at low doses, BQ-123 might be a more sensitive pharmacological tool for the detection of abnormal endothelin-1 mediated constriction.