TRPV4 (Transient Receptor Potential Vanilloid 4) Mediates Endothelium-Dependent Contractions in the Aortas of Hypertensive MiceNovelty and Significance [Vessels]

The role of TRPV4 (transient receptor potential vanilloid 4) in regulating vascular contraction in hypertensive mice is poorly established. We tested the hypothesis that TRPV4 regulates endothelium-dependent contractions in aortas from hypertensive mice through the activation of cytosolic cPLA2 (phospholipase A2) and COX2 (cyclooxygenase 2) and identified the possible endothelium-derived contracting factor generated by COX2. Using myography, we demonstrated that GSK1016790A (a TRPV4 agonist) and acetylcholine (ACh) trigger endothelium-dependent contractions in aortas from hypertensive mice, and the contractions were abolished with TRPV4 deletion. PLA2 assay and Western blotting showed that cPLA2 activity was higher in salt-induced hypertension and HC067047 or a Ca2+ chelator inhibited cPLA2 activity. Contractions induced by TRPV4 and ACh were inhibited by the cPLA2 inhibitor or removal of extracellular Ca2+. COX2 expression was enhanced in the endothelium from hypertensive mice and contractions induced by TRPV4 or ACh were inhibited by the COX2 inhibitor. Enzyme immunoassay showed that the release of prostaglandin F2α (PGF2α) was increased in hypertensive mice. GSK1016790A or ACh triggered the release of PGF2α and this was inhibited by HC067047, the cPLA2 inhibitor, and COX2 inhibitor. GSK1016790A, ACh, and PGF2α induced contractions were significantly reduced by S18886 in salt-induced hypertensive mice. The present study demonstrates that PGF2α generated by COX2 in the ...
Source: Hypertension - Category: Cardiology Authors: Tags: Basic Science Research, Ion Channels/Membrane Transport, Mechanisms, Vascular Biology, Hypertension Original Articles Source Type: research