title: Aurantio-obtusin relaxes systemic arteries through endothelial PI3K/AKT/eNOS-dependent signaling pathway in rats.
abstract: 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.
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, PR China.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, PR China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liao
authors.affiliation: College of Food, Northeast Agriculture University, PR China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University-Daqing, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University-Daqing, PR China. Electronic address: dalingz@yahoo.com.
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000959:Antihypertensive Agents; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D000960:Hypolipidemic Agents; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000880:Anthraquinones; D000959:Antihypertensive Agents; D000960:Hypolipidemic Agents; C000595611:aurantio-obtusin; D019001:Nitric Oxide Synthase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Aurantio-obtusin; Mesenteric artery; Nitric oxide synthase; PI3K/Akt pathway; Vasorelaxation