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

Author:

Wynne Brandi M.12,Labazi Hicham13,Lima Victor V.14,Carneiro Fernando S.15,Webb R. Clinton1,Tostes Rita C.15,Giachini Fernanda R.14

Affiliation:

1. Department of Physiology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA.

2. Department of Medicine, Nephrology, Emory University, Atlanta, GA 30322, USA.

3. Center for Cardiovascular Research, The Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA.

4. Institute of Biological Sciences and Health, Federal University of Mato Grosso – Barra do Garças – MT – Brazil; 78600-000.

5. Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; 14049-900.

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 Nω-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-κB, 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.

Publisher

Canadian Science Publishing

Subject

Physiology (medical),Pharmacology,General Medicine,Physiology

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