Nitro-oleic acid inhibits angiotensin II-induced hypertension.

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.

• Authors: Jifeng Zhang, Luis Villacorta, Lin Chang, Zhenzhen Fan, Milton Hamblin, Tianqing Zhu, Chen S Chen, Marsha P Cole, Francisco J Schopfer, Cheri X Deng, Minerva T Garcia-Barrio, Ying-Hong Feng, Bruce A Freeman, Y Eugene Chen
• Journal: Circulation research (Circ Res) Vol. 107 Issue 4 Pg. 540-8 (Aug 20 2010) ISSN: 1524-4571 [Electronic] United States
• PMID: 20558825 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 10-nitro-9,12-octadecadienoic acid
• 10-nitro-oleic acid
• Linoleic Acids
• Nitro Compounds
• Oleic Acids
• Angiotensin II
• Oleic Acid

Topics

• Angiotensin II (antagonists & inhibitors, physiology, toxicity)
• Animals
• Blood Pressure (drug effects, physiology)
• Hypertension (chemically induced, physiopathology, prevention & control)
• Linoleic Acids (therapeutic use)
• Mice
• Mice, Inbred C57BL
• Nitro Compounds (therapeutic use)
• Oleic Acid (therapeutic use)
• Oleic Acids (therapeutic use)
• Rats
• Rats, Sprague-Dawley