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Circ Res. 2010 Aug 20;107(4):540-8. doi: 10.1161/CIRCRESAHA.110.218404. Epub 2010 Jun 17.

Nitro-oleic acid inhibits angiotensin II-induced hypertension.

Author information

1
Cardiovascular Center, College of Engineering, University of Michigan, USA.

Abstract

RATIONALE:

Nitro-oleic acid (OA-NO(2)) is a bioactive, nitric-oxide derived fatty acid with physiologically relevant vasculoprotective properties in vivo. OA-NO(2) exerts cell signaling actions as a result of its strong electrophilic nature and mediates pleiotropic cell responses in the vasculature.

OBJECTIVE:

The present study sought to investigate the protective role of OA-NO(2) in angiotensin (Ang) II-induced hypertension.

METHODS AND RESULTS:

We show that systemic administration of OA-NO(2) results in a sustained reduction of Ang II-induced hypertension in mice and exerts a significant blood pressure lowering effect on preexisting hypertension established by Ang II infusion. OA-NO(2) significantly inhibits Ang II contractile response as compared to oleic acid (OA) in mesenteric vessels. The improved vasoconstriction is specific for the Ang II type 1 receptor (AT(1)R)-mediated signaling because vascular contraction by other G-protein-coupled receptors is not altered in response to OA-NO(2) treatment. From the mechanistic viewpoint, OA-NO(2) lowers Ang II-induced hypertension independently of peroxisome proliferation-activated receptor (PPAR)gamma activation. Rather, OA-NO(2), but not OA, specifically binds to the AT(1)R, reduces heterotrimeric G-protein coupling, and inhibits IP(3) (inositol-1,4,5-trisphosphate) and calcium mobilization, without inhibiting Ang II binding to the receptor.

CONCLUSIONS:

These results demonstrate that OA-NO(2) diminishes the pressor response to Ang II and inhibits AT(1)R-dependent vasoconstriction, revealing OA-NO(2) as a novel antagonist of Ang II-induced hypertension.

PMID:
20558825
PMCID:
PMC2937264
DOI:
10.1161/CIRCRESAHA.110.218404
[Indexed for MEDLINE]
Free PMC Article

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