Chen Yulong, Zhang Hongmei, Liu Huanhuan, Cao Ailan
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.
Medical Record Department, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China.
Biomed Rep. 2016 Oct;5(4):491-496. doi: 10.3892/br.2016.756. Epub 2016 Sep 12.
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 recorded on a myograph. The results showed that Sim concentration-dependently relaxed the superior mesenteric artery rings with endothelium pre-contracted by phenylephrine hydrochloride [maximum relaxation (E)=51.05±4.09%; negative logarithm of the concentration that caused 50% of the maximum response (pD)=4.17±0.18] or KCl (E=41.65±1.32%; pD=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 Ca-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 Ca influx.
辛伐他汀（Sim）除具有降脂特性外，还能诱导血管舒张；然而，其潜在机制仍不清楚。本研究旨在探讨辛伐他汀对大鼠肠系膜上动脉的血管舒张作用及其相关机制。在肌张力测定仪上记录大鼠肠系膜上动脉环的等长张力。结果表明，辛伐他汀能浓度依赖性地舒张由盐酸去氧肾上腺素预收缩的肠系膜上动脉环[最大舒张率（E）=51.05±4.09%；引起最大反应50%时的浓度的负对数（pD）=4.17±0.18]或氯化钾预收缩的环（E=41.65±1.32%；pD=3.55±0.1）。Nω-硝基-L-精氨酸甲酯（100 μM）显著抑制此作用，而1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（10 μM）和吲哚美辛（5 μM）对此无影响。在无内皮的动脉环中，4-氨基吡啶（100 μM）减弱了辛伐他汀诱导的血管舒张，但氯化钡（10 μM）、格列本脲（1M）和氯化四乙铵（1 mM）对此无影响。此外，辛伐他汀还抑制了在添加氯化钾（60 mM）的无钙培养基中因细胞外钙增加而引起的收缩。这些结果表明，辛伐他汀通过内皮依赖性途径诱导肠系膜上动脉环舒张，该途径涉及一氧化氮释放，还通过内皮非依赖性途径，该途径涉及电压依赖性钾通道开放和细胞外钙内流受阻。
