Downregulation of endothelial transient receptor potential vanilloid type 4 channel underlines impaired endothelial nitric oxide-mediated relaxation in the mesenteric arteries of hypertensive rats

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

Creator:

Boudaka, A. , Al-Suleimani, M., Al-Lawati, I., Baomar, H., Al-Siyabi, S. , and Zadjali, F.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:3a672b0b-ef40-4071-9642-1c1bdf116a4e
uuid:3a672b0b-ef40-4071-9642-1c1bdf116a4e
doi:10.33549/physiolres.933952

Subject:

TRPV4, Hypertension, Endothelium, Nitric oxide, and Spontaneously hypertensive rats

Type:

model:article and TEXT

Format:

bez média and svazek

Description:

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.

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Coverage:

219-231

Source:

Physiological research | 2019 Volume:68 | Number:2

Harvested from:

CDK

Metadata only:

false