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.
Sheng Li Xue Bao. 2017 Apr 25;69(2):129-134.
In order to explore the mechanisms underlying the vasoconstriction induced by blockade of inward rectifier K channels (K) with BaCl, myogenic tone of isolated rat coronary artery (RCA) was recorded with wire myograph. The dependence of BaCl- induced contraction on intracellular Ca ([Ca]) release and extracellular Ca ([Ca]) influx was studied by Ca deprivation and restoration. The mechanisms underlying BaCl-induced RCA contraction were investigated with specific inhibitors. BaCl (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 BaCl in Ca-free solution and by followed restoration of 2.5 mmol/L Ca 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 BaCl-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 BaCl induces vasoconstriction in RCA by enhancing both [Ca] release and [Ca] 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.
为了探究用氯化钡阻断内向整流钾通道（K）所诱导的血管收缩的潜在机制，用线肌张力测定仪记录了离体大鼠冠状动脉（RCA）的肌源性张力。通过剥夺钙和恢复钙来研究氯化钡诱导的收缩对细胞内钙（[Ca]）释放和细胞外钙（[Ca]）内流的依赖性。用特异性抑制剂研究了氯化钡诱导RCA收缩的机制。氯化钡（0.1 - 1.0 mmol/L）以浓度依赖性方式使离体RCA收缩，最大收缩力为（5.69±1.07）mN，几乎等同于60 mmol/L氯化钾诱导的收缩。在无钙溶液中由氯化钡诱导的收缩以及随后恢复2.5 mmol/L钙所诱导的收缩分别占（35.44±6.72）%和（64.56±5.94）%。钙通道阻滞剂硝苯地平（0.3 μmol/L）、环氧化酶抑制剂吲哚美辛（100 μmol/L）、ERK1/2抑制剂PD98059（10 μmol/L）和氯通道阻滞剂尼氟灭酸（100 μmol/L）预处理分别使氯化钡诱导的最大收缩力降低（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）。这些结果表明，氯化钡通过增强[Ca]释放和[Ca]内流诱导RCA血管收缩，并提示前列腺素合成增加、钙通道和氯通道的激活以及ERK1/2途径可能参与了这一过程。
