The endothelium contributes to the maintenance of vasodilator
tone by releasing endothelium-derived relaxing factors, including
nitric oxide (NO). In hypertension, endothelial nitric oxide
synthase (eNOS) produces less NO and could be one of the
contributing factors to the increased peripheral vascular
resistance. Agonist-induced Ca2+ entry is essential for the
activation of eNOS. The transient receptor potential vanilloid
type 4 (TRPV4) channel, a Ca2+-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,
4α-phorbol-12,13-didecanoate (4αPDD) was assessed in
mesenteric arteries obtained from Wistar-Kyoto (WKY) and
spontaneously hypertensive rats (SHRs). Compared to WKY, SHR
demonstrated a significantly attenuated 4αPDD-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 4αPDD-induced endothelium-dependent
NO-mediated vasorelaxation is reduced in SHR and downergulation of TRPV4 could be one of the contributing mechanisms.