Nitro-Oleic Acid Inhibits Angiotensin II-Induced Hypertension

Nitro-Oleic Acid Inhibits Angiotensin II-Induced Hypertension

J Zhang, L Villacorta, L Chang, Z Fan, M Hamblin, T Zhu, C. S Chen, M. P Cole, F. J Schopfer, C. X Deng, M. T Garcia Barrio, Y. H Feng, B. A Freeman and Y. E. Chen

Circulation Research, 2010, 107(4), 540-548. DOI: 10.1161/CIRCRESAHA.110.218404



Nitro-oleic acid (OA-NO2) is a bioactive, nitric-oxide derived fatty acid with physiologically relevant vasculoprotective properties in vivo. OA-NO2 exerts cell signaling actions as a result of its strong electrophilic nature and mediates pleiotropic cell responses in the vasculature.


The present study sought to investigate the protective role of OA-NO2 in angiotensin (Ang) II–induced hypertension.

Methods and Results:

We show that systemic administration of OA-NO2 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-NO2 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 (AT1R)-mediated signaling because vascular contraction by other G-protein–coupled receptors is not altered in response to OA-NO2 treatment. From the mechanistic viewpoint, OA-NO2 lowers Ang II–induced hypertension independently of peroxisome proliferation-activated receptor (PPAR) activation. Rather, OA-NO2, but not OA, specifically binds to the AT1R, reduces heterotrimeric G-protein coupling, and inhibits IP3 (inositol-1,4,5-trisphosphate) and calcium mobilization, without inhibiting Ang II binding to the receptor.


These results demonstrate that OA-NO2 diminishes the pressor response to Ang II and inhibits AT1R-dependent vasoconstriction, revealing OA-NO2 as a novel antagonist of Ang II–induced hypertension.

ASCI-ID: 1434-318