Potassium channel openers elicit endothelium‐dependent enhancement of nerve‐mediated vasoconstriction

Abstract

The vascular endothelium modulates arterial diameter via the release of diffusible relaxing and contracting factors and by direct electrical coupling with smooth muscle cells (endothelium‐dependent hyperpolarization; EDH). Hyperpolarization of the endothelial cell membrane potential facilitates Ca2+ influx through non‐selective cation channels and spreads electrotonically to the smooth muscle cells via gap junctions. We hypothesized that pharmacological activators of Ca2+‐activated potassium (KCa) would cause endothelium‐dependent attenuation of nerve‐mediated vasoconstriction in the rat perfused mesenteric bed. The presence of CYPPA, an activator of small conductance KCa channels, nerve‐mediated vasoconstriction was significantly attenuated in the endothelium‐intact perfused mesenteric bed. However, on washout, a rebound effect was observed with nerve‐mediated constriction significantly enhanced. Addition of indomethacin enhanced CYPPA‐induced depression of nerve‐evoked constriction but prevented the rebound increase in vasoconstriction. In endothelium‐denuded preparations, CYPPA caused a smaller depression of vasoconstriction also with no rebound. These data indicate that activators of KCa channels may activate both endothelium‐dependent dilator and contractile pathways. Supported by HSFC.