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.
The inhibitory action of perivascular adipose tissue (PVAT) in modulation of arterial contraction has been recently recognized and contrasted with the prohypertensive effect of obesity in humans. In this study we demonstrated that PVAT might have opposing effect on sympatho-adrenergic contractions in different rat conduit arteries. In superior mesenteric artery isolated from normotensive Wistar-Kyoto rats (WKY), PVAT exhibited inhibitory influence on the contractions to exogenous noradrenaline as well as to endogenous noradrenaline released from art
erial sympathetic nerves during transmural electrical stimulation or
after application of tyramine. In contrast, the abdominal aortawith intact PVAT responded with larger contractions to transmural electrical stimulation and tyramine when compared to the aorta after removing PVAT; the
responses to noradrenalinewere similar in both. This indicates that PVAT may contain additional sources of endogenous noradrenaline which could be responsible for the main difference in the modulatory effect of PVAT on adrenergic contractions between abdominal aortas and superior mesenteric arteries. In spontaneously hypertensive rats
(SHR), the anticontractile effect of PVAT in mesenteric arteries was reduced, and the removal of PVAT completely eliminated the difference in the dose-response curves to exogenous noradrenaline between SHR and WKY. These results suggest that in mesenteric artery isolated from SHR, the impairedanticontractile influence of PVAT might significantly contribute to
its increased sensitivity to adrener
gic stimuli.