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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

Received: 2016-10-19　　Accepted: 2017-02-07

Corresponding author: 张明升　　E-mail: 4156589@sina.com

Citing This Article：

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).