Contribution of endothelin and its receptors to the regulation of vascular tone during exercise is different in the systemic, coronary and pulmonary circulation.

Abstract

Exercise-induced vasodilation is thought to be mediated through various vasodilator substances, but blunting the influence of vasoconstrictors such as ET may also play a role. However, the role of ET and its receptors in the regulation of systemic, pulmonary and coronary vascular resistance is incompletely understood. The aim of this study was to identify the contribution of ET-1 through the ET(A) and ET(B) receptors to the regulation of tone in the systemic, coronary and pulmonary beds at rest and during exercise. Ten chronically instrumented swine were studied while running on a treadmill before and after ET(A) blockade (EMD122946) or ET(AB) blockade (tezosentan). At rest, EMD122946 resulted in vasodilation in the coronary and systemic circulation, evidenced by a decrease in coronary and systemic vascular resistance and an increase in coronary and mixed venous O(2)-saturation. These effects waned during exercise. The effect of tezosentan on the systemic vasculature was similar to that of EMD122946, whereas it was smaller in the coronary circulation. EMD122946 had no effect on the pulmonary vasculature, whereas tezosentan decreased pulmonary resistance but only during exercise. ET exerts a constrictor influence on the coronary and systemic circulation through the ET(A)-receptor, which decreases during exercise thereby contributing to metabolic vasodilation. ET exerts a tonic vasodilator influence on coronary resistance vessels through the ET(B)-receptor. Finally, ET exerts an ET(B)-mediated constrictor influence in the pulmonary vasculature during exercise.