Year: 2010
Type: article
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.
Source: Circulation Research
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Redox-Derived Pulmonary Anti-Inflammatory Mediators, G1250753618, Mechanisms of ultrasound mediated intracellular drug and gene delivery, Nitroalkenes and Blood Pressure Regulation, Redox Transduction of Nitric Oxide Signaling, Nitric Oxide Regulation of Vascular Oxidant Injury, CRP Biology and Vascular Disease, Nitro-Fatty Acids and Nrf2 in Vascular Remodeling, PPAR-gamma and Vascular Disease, Metabolic Stress-Induced Fatty Acid Nitration and Cardiovascular Function, Advanced Ultrasound Ablation Therapy for Atrial Fibrillation, PPAR-delta in obesity-related vascular remodeling
OpenAlex ID: W2097005377