Natural Product Extract of Dicksonia sellowiana Induces Endothelium-Dependent Relaxations by a Redox-Sensitive Src- and Akt-Dependent Activation of eNOS in Porcine Coronary Arteries

作者：Rattmann Yanna D; Anselm Eric; Kim Jong Hun; Dal Ros Stephanie; Auger Cyril; Miguel Obdulio G; Santos Adair R S; Chataigneau Thierry; Schini Kerth Valerie B^*

来源：Journal of Vascular Research, 2012, 49(4): 284-298.

DOI：10.1159/000336647

• Dicksonia sellowiana
• Porcine coronary artery
• Endothelium
• PI3-kinase/Akt pathway
• Nitric oxide

Background/Aims: The consumption of polyphenol-rich food is associated with a decreased mortality from coronary diseases. This study examined whether a standardized hydroalcoholic extract of Dicksonia sellowiana (HEDS) triggered endothelium-dependent relaxations in porcine coronary artery rings and characterized the underlying mechanism. Methods: The phosphorylation level of Src, Akt and eNOS was assessed by Western blot analysis, the formation of reactive oxygen species by dihydroethidine staining and the level of eNOS Ser1177 phosphorylation by immunohistochemical staining in sections of coronary arteries. Results: HEDS-induced endothelium-dependent relaxations were strongly reduced by N omega-nitro-L-arginine, an eNOS inhibitor, and by its combination with charybdotoxin plus apamin, inhibitors of endothelium-derived hyperpolarizing factor-mediated responses. These relaxations were markedly reduced by MnTMPyP (a membrane-permeant mimetic of superoxide dismutase), polyethylene glycol catalase (PEG-catalase; a membrane-permeant analog of catalase), and by wortmannin (an inhibitor of PI3-kinase). HEDS-induced sustained phosphorylation of Akt and eNOS in endothelial cells was abolished by MnIMPyP, PEG-catalase and wortmannin. Oral administration of HEDS induced a significant decrease of mean arterial pressure in spontaneously hypertensive rats. Conclusion: These findings indicate that HEDS caused endothelium-dependent relaxations of coronary artery rings through the redox-sensitive activation of the endothelial PI3-kinase/Akt pathway leading to the subsequent activation of eNOS by phosphorylation. HEDS also has antihypertensive properties.

• 出版日期2012