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The transient receptor potential vanilloid type 4 (TRPV4) channel, a Ca(2+)-permeant cation channel, is expressed in the endothelial cells and involved in the regulation of vascular tone. The present study aimed to investigate the role of TRPV4 channel in endothelium-dependent NO-mediated relaxation of the resistance artery in hypertensive rats. Using a wire myograph, relaxation response to the TRPV4 activator, 4alpha-phorbol-12,13-didecanoate (4alphaPDD) was assessed in mesenteric arteries obtained from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). Compared to WKY, SHR demonstrated a significantly attenuated 4alphaPDD-induced endothelium-dependent NO-mediated relaxation. Immunohistochemical analysis revealed positive staining for TRPV4 in the endothelium of mesenteric artery sections in both WKY and SHR. Furthermore, TRPV4 mRNA and protein expressions in SHR were significantly lower than their expression levels in WKY rats. We conclude that 4alphaPDD-induced endothelium-dependent NO-mediated vasorelaxation is reduced in SHR and downregulation of TRPV4 could be one of the contributing mechanisms.<\/jats:p>","DOI":"10.33549\/physiolres.933952","type":"journal-article","created":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T22:09:41Z","timestamp":1556316581000},"page":"219-231","source":"Crossref","is-referenced-by-count":23,"title":["Downregulation of endothelial transient receptor potential vanilloid type 4 channel underlines impaired endothelial nitric oxide-mediated relaxation in the mesenteric arteries of hypertensive rats"],"prefix":"10.33549","author":[{"given":"A.","family":"Boudaka","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khoud, Sultanate of Oman. boudaka@squ.edu.om"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Al-Suleimani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Al-Lawati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Baomar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Al-Siyabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"19169","published-online":{"date-parts":[[2019,4,26]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"ADDISON MP, SINGH TU, PARIDA S, CHOUDHURY S, KASA JK, SUKUMARAN SV, DARZI SA, KANDASAMY K, SINGH V, KUMAR D, MISHRA SK: NO synthase inhibition attenuates EDHF-mediated relaxation induced by TRPV4 channel agonist GSK1016790A in the rat pulmonary artery: Role of TxA2. 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