Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8528927 | European Journal of Pharmacology | 2018 | 22 Pages |
Abstract
Acute coronary arterial spasm is contributory to ethanol-induced heart ischemic events. The present experiments were designed to study contractive effect of ethanol in isolated rat coronary arteries (RCAs) stimulated mildly with vasoconstrictors and involvement of voltage-gated potassium (KV) channels and mitogen-activated protein kinases (MAPKs) of rat coronary arterial smooth muscle cell (RCASMC) in the spasm. The vascular tension was recorded with a wire myograph. KV currents of single freshly isolated RCASMC were assessed with patch clamp. Phosphorylation of RCASMC MAPKs (p38 MAPK and p44/42 MAPK) was assayed by Western blots. Mild stimulation, which was defined as 5-20% of 60â¯mM KCl-induced contraction, with thromboxane A2 mimetic U46619, endothelin-1 or KCl tremendously increased contractive response of RCAs to ethanol (0.8-8.0â¯mg/ml). Ethanol (8 and 25â¯mg/ml) reduced the maximal KV currents by 53.6% and 56.6% respectively without concentration-dependence. Both ethanol (8.0â¯mg/ml) and U46619 (0.3â¯Î¼M) enhanced phosphorylation of p38 MAPK and p44/42 MAPK and there was a pronounced synergism between them. MAPK pathway inhibition with p38 MAPK inhibitor SB239063 and p44/42 MAPK inhibitor PD98059 depressed ethanol-induced contraction by 22-55% in the stimulated RCAs and almost abrogated ethanol-induced reduction in KV currents. The present results for the first time demonstrated that ethanol induces potent vasoconstriction in stimulated RCAs and depresses KV currents in RCASMCs. It is suggested that MAPKs pathways play an important role in the etiology of ethanol-induced coronary artery diseases.
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Authors
Rong Yang, Yu Liu, Xiaomin Hou, Yanying Fan, Jie Li, Min Chen, Yan Wang, Xuanping Zhang, Mingsheng Zhang,