Endothelin-1-mediated vasoconstriction at rest and during dynamic exercise in healthy humans

Abstract

It is now generally accepted that α-adrenoreceptor-mediated vasoconstriction is attenuated during exercise, but the efficacy of nonadrenergic vasoconstrictor pathways during exercise remains unclear. Thus, in eight young (23 ± 1 yr), healthy volunteers, we contrasted changes in leg blood flow (ultrasound Doppler) before and during intra-arterial infusion of the α1-adrenoreceptor agonist phenylephrine (PE) with that of the nonadrenergic endothelin A (ETA)/ETBreceptor agonist ET-1. Heart rate, arterial blood pressure, common femoral artery diameter, and mean blood velocity were measured at rest and during knee-extensor exercise at 20%, 40%, and 60% of maximal work rate (WRmax). Drug infusion rates were adjusted for blood flow to maintain comparable doses across all subjects and conditions. At rest, PE infusion (8 ng·ml−1·min−1) provoked a rapid and significant decrease in leg blood flow (−51 ± 3%) within 2.5 min. Resting ET-1 infusion (40 pg·ml−1·min−1) significantly decreased leg blood flow within 5 min, reaching a maximal vasoconstriction (−34 ± 3%) after 25–30 min of continuous infusion. Compared with rest, an exercise intensity-dependent attenuation to PE-mediated vasoconstriction was observed (−18 ± 5%, −7 ± 2%, and −1 ± 3% change in leg blood flow at 20%, 40%, and 60% of WRmax, respectively). Vasoconstriction in response to ET-1 was also blunted in an exercise intensity-dependent manner (−13 ± 3%, −7 ± 4%, and 2 ± 3% change in leg blood flow at 20%, 40%, and 60% of WRmax, respectively). These findings support a significant contribution of ET-1 and α-adrenergic receptors in the regulation of skeletal muscle blood flow in the human leg at rest and suggest a similar, intensity-dependent “lysis” of peripheral ET and α-adrenergic vasoconstriction during dynamic exercise.