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内向整流钾通道阻滞剂BaCl₂引起大鼠冠状动脉收缩的机制

范芳文, 贺泽芳, 石萌, 杨蓉, 侯晓敏, 刘宇, 张明升^*

山西医科大学基础医学院药理学教研室，太原 030001

摘要

为了探讨内向整流钾通道(inward rectifier K⁺ channels, Kir)阻滞剂BaCl2引起大鼠冠状动脉(rat coronary artery, RCA)收缩的作用机制，本研究采用离体微血管环张力记录法观察BaCl2引起的RCA收缩对细胞内Ca2+ ([Ca2+]i)释放和细胞外Ca2+ ([Ca2+]o)内流的依赖性，并通过抑制剂实验探讨其作用机制。结果显示，静息状态下，BaCl2 (0.1~1.0 mmol/L)浓度依赖性地收缩离体RCA，最大收缩幅度为(5.69 ± 1.07) mN，与KCl (60 mmol/L)收缩幅度相近；BaCl2在无钙液中所引起的收缩占其总收缩的(35.44 ± 6.72)%，复钙进一步引起(64.56 ± 5.94)%的收缩；钙通道阻滞剂硝苯地平(0.3 μmol/L)、环氧合酶抑制剂吲哚美辛(100 μmol/L)、细胞外信号调节激酶ERK1/2抑制剂PD98059 (10 μmol/L)和氯通道阻滞剂尼氟灭酸(100 μmol/L)分别使BaCl2引起的RCA最大收缩幅度降低(87.82 ± 5.43)% (P < 0.01)、(73.23 ± 5.47)% (P < 0.01)、(75.69 ± 7.94)% (P < 0.01)和(83.24 ± 7.69)% (P < 0.01)。上述实验结果表明，BaCl2引起RCA收缩依赖于[Ca2+]i释放和[Ca2+]o内流，并提示该过程与增加前列腺素类物质合成、钙通道和氯通道激活及ERK1/2通路有关。

关键词： 氯化钡; 内向整流钾通道 ; 冠状动脉 ; 前列腺素类 ; 氯通道 ; 钙离子 ; ERK1/2通路

分类号：R322

Mechanisms underlying rat coronary arterial vasoconstriction induced byblockade of inward rectifier potassium channels with BaCl₂

FAN Fang-Wen, HE Ze-Fang, SHI Meng, YANG Rong, HOU Xiao-Min, LIU Yu, ZHANG Ming-Sheng^*

Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, China

Abstract

In order to explore the mechanisms underlying the vasoconstriction induced by blockade of inward rectifier K+ channels (Kir) with BaCl₂, myogenic tone of isolated rat coronary artery (RCA) was recorded with wire myograph. The dependence of BaCl2- induced contraction on intracellular Ca2+ ([Ca2+]i) release and extracellular Ca2+ ([Ca2+]o) influx was studied by Ca2+ deprivation and restoration. The mechanisms underlying BaCl2-induced RCA contraction were investigated with specific inhibitors. BaCl2 (0.1–1.0 mmol/L) contracted isolated RCA in a concentration-dependent manner and the maximal contraction was (5.69 ± 1.07) mN, nearly equal to contraction induced by 60 mmol/L KCl. The contractions induced by BaCl2 in Ca2+-free solution and by followed restoration of 2.5 mmol/L Ca2+ accounted for (35.44 ± 6.72)% and (64.56 ± 5.94)%, respectively. Calcium channel blocker nifedipine (0.3 μmol/L), cyclooxygenase inhibitor indomethacin (100 μmol/L), ERK1/2 inhibitor PD98059 (10 μmol/L) and chloride channel blocker niflumic acid (100 μmol/L) pretreatment depressed the BaCl2-induced maximal contraction by (87.82 ± 5.43)% (P < 0.01), (73.23 ± 5.47)% (P < 0.01), (75.69 ± 7.94)% (P < 0.01) and (83.24 ± 7.69)% (P < 0.01), respectively. These results demonstrate that BaCl2 induces vasoconstriction in RCA by enhancing both [Ca2+]i release and [Ca2+]o influx, and suggest that increase of prostanoids synthesis, activation of calcium channels and chloride channels, as well as ERK1/2 pathway may be involved in this process.

Key words: BaCl2; inward rectifier K+ channels ; coronary artery ; prostanoids ; chloride channels ; Ca2+ ; ERK1/2 pathway

收稿日期：2016-10-19　　录用日期：2017-02-07

通讯作者：张明升　　E-mail: 4156589@sina.com

引用本文：

范芳文, 贺泽芳, 石萌, 杨蓉, 侯晓敏, 刘宇, 张明升. 内向整流钾通道阻滞剂BaCl₂引起大鼠冠状动脉收缩的机制[J]. 生理学报 2017; 69 (2): 129-134.

FAN Fang-Wen, HE Ze-Fang, SHI Meng, YANG Rong, HOU Xiao-Min, LIU Yu, ZHANG Ming-Sheng. Mechanisms underlying rat coronary arterial vasoconstriction induced byblockade of inward rectifier potassium channels with BaCl₂. Acta Physiol Sin 2017; 69 (2): 129-134 (in Chinese with English abstract).