Mesenteric arteries from stroke-prone spontaneously hypertensive rats exhibit an increase in nitric-oxide-dependent vasorelaxation

Author(s)

Wynne, Brandi M. ^{[1, 2]} ; Labazi, Hicham ^{[1, 3]} ; Lima, Victor V. ^{[4, 1]} ; Carneiro, Fernando S. ^{[1, 5]} ; Webb, R. Clinton ^[1] ; Tostes, Rita C. ^{[1, 5]} ; Giachini, Fernanda R. ^{[4, 1]}

Affiliation

^[1] Augusta Univ, Med Coll Georgia, Dept Physiol, Augusta, GA 30912 - USA

^[2] Emory Univ, Dept Med, Nephrol, Atlanta, GA 30322 - USA

^[3] Nationwide Childrens Hosp, Res Inst, Ctr Cardiovasc Res, Columbus, OH 43205 - USA

^[4] Univ Fed Mato Grosso, Inst Biol Sci & Hlth, BR-78600000 Barra Do Garcas, MT - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Canadian Journal of Physiology and Pharmacology; v. 96, n. 8, p. 719-727, AUG 2018.
• Web of Science Citations: 1

Abstract

The endothelium is crucial for the maintenance of vascular tone by releasing several vasoactive substances, including nitric oxide (NO). Systemic mean arterial pressure is primarily regulated by the resistance vasculature, which has been shown to exhibit increased vascular reactivity, and decreased vasorelaxation during hypertension. Here, we aimed to determine the mechanism for mesenteric artery vasorelaxation of the stroke-prone spontaneously hypertensive rat (SHRSP). We hypothesized that endothelial NO synthase (eNOS) is upregulated in SHRSP vessels, increasing NO production to compensate for the endothelial dysfunction. Concentration-response curves to acetylcholine (ACh) were performed in second-order mesenteric arteries; we observed decreased relaxation responses to ACh (maximum effect elicited by the agonist) as compared with Wistar-Kyoto (WKY) controls. Vessels from SHRSP incubated with N omega-nitro-L-arginine methyl ester and (or) indomethacin exhibited decreased ACh-mediated relaxation, suggesting a primary role for NO-dependent relaxation. Vessels from SHRSP exhibited a significantly decreased relaxation response with inducible NO synthase (iNOS) inhibition, as compared with WKY vessels. Western blot analysis showed increased total phosphorylated NF-kappa B, and phosphorylated and total eNOS in SHRSP vessels. Overall, these data suggest a compensatory role for NO by increased eNOS activation. Moreover, we believe that iNOS, although increasing NO bioavailability to compensate for decreased relaxation, leads to a cycle of further endothelial dysfunction in SHRSP mesenteric arteries. (AU)

• FAPESP's process: 10/52214-6 - Contribution of oxidative stress and NOXes to diabetes-associated vascular and renal injury
• Grantee: Rita de Cassia Aleixo Tostes Passaglia
• Support Opportunities: Regular Research Grants