Angiotensin II induces endothelial dysfunction by downregulating TRPV4 channels

Abstract

Angiotensin II (Ang II) is a potent vasoconstrictor of vascular smooth muscle cells and implicated in hypertension, but it’s role in the regulation of endothelial function is not well known. We and others have previously shown that mechanosensitive ion channel, TRPV4 mediates flow- and/or receptor-dependent vasodilation via nitric oxide (NO) production in endothelial cells. Ang II was demonstrated to crosstalk with TRPV4 via AT1R and beta-arresting signaling in epithelial and immortalized cells, however, the role of this crosstalk in endothelial cell function is unexplored. Here, we demonstrate that pre-treatment with Ang II (200 nM for 48 h) significantly abolished TRPV4 mediated calcium influx in human microvascular endothelial cells, HMEC-1 (human EC). Further, Ang II treatment significantly downregulated TRPV4 protein expression in human EC without altering TRPV4 mRNA levels. Furthermore, Ang II-treatment significantly inhibited TRPV4-induced eNOS phosphorylation in human EC. Taken together, these results suggest that Ang II, in addition to eliciting smooth muscle contraction, contributes to hypertension by reducing TRPV4 protein expression and dependent NO production in human EC. This work is supported by NIH (1RO1HL119705, 1R15CA202847-01 and R01 HL148585), AHA Grant in Aid (14GRNT20380935, AHA- TPA-971237) and start-up funds from University of Toledo (CKT). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.