Vascular tone is regulated by endothelium-derived vasodilating and constricting substances, mainly nitric oxide and endothelin (ET)-1. These 2 mediators, which antagonize the actions of each other, are released in response to shear-stress produced by blood flow. The aim of this study was to delineate the contribution of endogenous ET-1 on vascular tone of a large conduit artery during reduced and hyperemic flow. Radial artery diameter was continuously measured with a high-resolution ultrasonic echo-tracking device in 8 healthy subjects. After establishing stable baseline conditions, a wrist cuff was inflated to suprasystolic pressure for 5 minutes. In another 5 subjects, measurements were obtained during intraarterial infusion of saline or an ETA receptor antagonist (BQ-123, 1 nmol/min) in a dosage not affecting basal radial diameter. Wrist occlusion caused a progressive vasoconstriction of the radial artery (P = 0.0001). Vasoconstriction of the radial artery during wrist occlusion was significantly attenuated by ETA receptor antagonism (-2.7% +/- 0.6% versus -6.8% +/- 0.6% during saline, P = 0.007). Flow-mediated vasodilation was not influenced by BQ-123 (7.5% +/- 0.8% versus 7.8% +/- 1.1%, P = NS). This study demonstrates active vasoconstriction of large conduit arteries during conditions of reduced blood flow via ETA receptoractivation. This may play an important role in disease states with reduced systemic or local blood flow and indicates the therapeutic potential of ETA receptor antagonism.