Endothelial Cell TRPV4 Channels Turn to the Dark Side During Hypertension

In this issue of Hypertension, Zhang et al 1 investigated the regulation of intracellular calcium (Ca 2+ ) signaling in endothelial cells and vascular reactivity in flat-mounted (en face) arteries of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) control rat arteries.They found that the expression of Transient Receptor Potential Vanilloid 4 (TRPV4) channels was higher in mesenteric artery endothelial cells of SHR than WKY rats.They also showed that endothelial cell TRPV4 channels stimulated vasodilation in arteries during normotension, but differentially modulated arterial contractility during genetic hypertension.1 This functional switch occurred because endothelial cell TRPV4 channels shifted from producing oscillatory Ca 2+ signals during normotension to generating sustained Ca 2+ signals at high channel activity during hypertension.This study provides important new information regarding the regulation of arterial contractility by endothelial cell TRPV4 channels and illustrates the mechanisms by which vasodilatory signaling can become contractile during hypertension.