Red wine polyphenols‐induced, endothelium‐dependent NO‐mediated relaxation is due to the redox‐sensitive PI3‐kinase/Akt‐dependent phosphorylation of endothelial NO‐synthase in the isolated porcine coronary artery

Abstract

An enhanced endothelial formation of nitric oxide (NO) by red wine polyphenolic compounds (RWPs) has been involved in the protective effect of chronic intake of red wine on coronary diseases. However, the mechanism underlying the activation of endothelial NO synthase (eNOS) remains unclear. In the presence of indomethacin and charybdotoxin plus apamin to prevent the formation of prostanoids and endothelium-derived hyperpolarizing factor, respectively, RWPs caused pronounced endothelium-dependent relaxations in porcine coronary arteries. Relaxations to RWPs were abolished by N(omega)-nitro-L-arginine (L-NA, a competitive inhibitor of NO synthase) and the membrane permeant analog of superoxide dismutase (SOD), MnTMPyP, and reduced by polyethylene glycol-SOD (PEG-SOD), PEG-catalase and inhibitors of PI3-kinase (wortmannin and LY294002). RWPs caused the L-NA-sensitive formation of NO, as assessed by electron spin resonance spectroscopy and the formation of cyclic guanosine monophosphate in coronary artery endothelial cells; these responses were reduced by MnTMPyP, PEG-catalase, and inhibitors of PI3-kinase. RWPs caused the sustained phosphorylation of Akt and eNOS at Ser1177 in endothelial cells, which were abolished by MnTMPyP and inhibitors of PI3-kinase. These data demonstrate that RWPs induce the redox-sensitive activation of the PI3-kinase/Akt pathway in endothelial cells which, in turn, causes phosphorylation of eNOS, resulting in an increased formation of NO.

Endothelium-independent and endothelium-dependent vasorelaxation by a dichloromethane fraction from <i>Anogeissus leiocarpus</i> (dc) <i>guill</i>. Et <i>Perr. (combretaceae)</i>: possible involvement of cyclic nucleotide phosphodiesterase inhibition

“…The inhibition of EDHF-mediated responses with charybdotoxin plus apamin did not affect relaxations to ALF. In contrast to red wine extract (Ndiaye et al 2005), the relaxation to ALF persisted in the presence of the combination L-NA, charybdotoxin and apamin on pig coronary artery. The persistent relaxation to ALF was not due to the formation of relaxing prostanoids; since all experiments were performed in the presence of indomethacin.…”

Resveratrol Ameliorates Clonidine-Induced Endothelium-Dependent Relaxation Involving Akt and Endothelial Nitric Oxide Synthase Regulation in Type 2 Diabetic Mice

“…3), although this acute activation of eNOS is consistent with a previous report showing that RV induced endothelial NO production. [34][35][36] The effect of RV on the endothelium resembles that of clonidine, an α 2 -adrenergic receptor agonist. In our previous study, we reported that the clonidine-induced relaxation response in DM mice decreased through the inactivation of the Akt/eNOS signaling pathway.…”

Angiotensin II-Induced Hypertension Is Associated with a Selective Inhibition of Endothelium-Derived Hyperpolarizing Factor-Mediated Responses in the Rat Mesenteric Artery

“…Acetylcholine is mainly dependent on an increase in intracellular free calcium concentration in endothelial cells. RWPs have been shown to induce arterial relaxations, mainly through the redox-sensitive activation of the PI3-kinase pathway (Ndiaye et al, 2004(Ndiaye et al, , 2005. Therefore, we sought to verify whether angiotensin II is able to discriminate the two distinct endothelial intracellular pathways in response to the two stimuli, acetylcholine and RWPs.…”