title: Mechanisms of simvastatin-induced vasodilatation of rat superior mesenteric arteries.
abstract: Independent of its lipid-lowering properties, simvastatin (Sim) induces vasorelaxation; however, the underlying mechanisms have remained elusive. The aim of the present study was to investigate the vasorelaxant effects of Sim on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recordedin vitroon a myograph. The results showed that Sim concentration-dependently relaxed the superior mesenteric artery rings with endothelium pre-contracted by phenylephrine hydrochloride [maximum relaxation (Emax)=51.05±4.09%; negative logarithm of the concentration that caused 50% of the maximum response (pD2)=4.17±0.18] or KCl (Emax=41.65±1.32%; pD2=3.55±0.1). Nω-nitro-L-arginine methyl ester (100 µM) significantly inhibited this effect, while it was not affected by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 µM) and indomethacin (5 µM). In artery rings without endothelium, vasorelaxation induced by Sim was attenuated by 4-aminopyridine (100 µM), but was not affected by barium chloride dehydrate (10 µM), glibenclamide (10 µM) and traethylammonium chloride (1 mM). Moreover, Sim also inhibited the contraction induced by increasing external calcium in Ca2+-free medium with added KCl (60 mM). These results suggested that Sim induces relaxation of superior mesenteric arterial rings through an endothelium-dependent pathway, involving nitric oxide release and also through an endothelium-independent pathway, involving the opening of voltage-dependent K+channels and blockade of extracellular Ca2+influx.
authors.affiliation: Shaanxi Pharmaceutical Development Center, Shaanxi Pharmaceutical Holding Group Co., Ltd., Xi'an, Shaanxi 710075, P.R. China; Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Medical Record Department, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Shaanxi Pharmaceutical Development Center, Shaanxi Pharmaceutical Holding Group Co., Ltd., Xi'an, Shaanxi 710075, P.R. China; Preparation Research Room, Shaanxi Chinese Medicine Institute, Xianyang, Shaanxi 712000, P.R. China.
authors.forename: Ailan
authors.initials: A
authors.lastname: Cao
keywords: Ca2+ influxs; K+ channel; nitric oxide; simvastatin; vasorelaxant effects