Aurantio-obtusin relaxes systemic arteries through endothelial PI3K/AKT/eNOS-dependent signaling pathway in rats

Aurantio-obtusin is a natural effective compound isolated from semen cassiae,which possesses hypotensive and hypolipidemic effects. although its hypotensive effect have been clarified,mechanisms aurantio-obtusin relaxes systemic arteries remain unclear. this study was to investigate effects and mechanisms of aurantio-obtusin on isolated mesenteric arteries (mas). we examined mas relaxation induced by aurantio-obtusin on rat isolated mas,expression and activity of endothelial nitric oxide synthase (enos) and protein kinase b (akt),and nitric oxide (no) production in bovine artery endothelial cells (baecs). findings showed aurantio-obtusin elicited dose-dependent vasorelaxation with phenylephrine (pe) precontracted rat ma rings (diameter: 200-300 μm),which can be diminished by denudation of endothelium and inhibition of enos activity,while having no effect on rat isolated pulmonary artery (pa) rings. aurantio-obtusin increased no production by promoting phosphorylations of enos at ser-1177 and thr-495 in endothelial cells. aurantio-obtusin also promoted phosphorylations of akt at ser-473. pi3k inhibitor ly290042 could diminish vasorelaxation induced by aurantio-obtusin. moreover aurantio-obtusin also elicited dose-dependent vasorelaxation effect with pe precontracted ma rings (diameter: 100-150 μm). therefore,vasorelaxation induced by aurantio-obtusin was dependent on endothelium integrity and no production,which mediated by endothelial pi3k/akt/enos pathway. results suggest aurantio-obtusin may offer therapeutic effects in hypertension,as a new potential vasodilator. © 2015 production and hosting by elsevier b.v. on behalf of japanese pharmacological society.