Mechanisms of simvastatin-induced vasodilatation of rat superior mesenteric arteries

Chen,Yulong; Zhang,Hongmei; Liu,Huanhuan; Cao,Ailan

doi:10.3892/br.2016.756

October-2016 Volume 5 Issue 4

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October-2016 Volume 5 Issue 4

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Article

Mechanisms of simvastatin-induced vasodilatation of rat superior mesenteric arteries

Authors:
- Yulong Chen
- Hongmei Zhang
- Huanhuan Liu
- Ailan Cao
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Affiliations: Shaanxi Pharmaceutical Development Center, Shaanxi Pharmaceutical Holding Group Co., Ltd., Xi'an, Shaanxi 710075, P.R. China, Medical Record Department, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, 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, Shannxi Pharmaceutical Development Center, Shaanxi Pharmaceutical Holding Group Co., Ltd., Xi'an, Shaanxi 710075, P.R. China
Pages: 491-496
|
Published online on: September 12, 2016

https://doi.org/10.3892/br.2016.756
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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 recorded in vitro 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 (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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Mechanisms of simvastatin-induced vasodilatation of rat superior mesenteric arteries

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