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为了探讨内向整流钾通道(inward rectifier K~+channels,K_(ir))阻滞剂BaCl_2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BaCl_2引起的RCA收缩对细胞内Ca~(2+)([Ca~(2+)]_i)释放和细胞外Ca~(2+)([Ca~(2+)]_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,BaCl_2(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)m N,与KCl(60 mmol/L)收缩幅度相近;BaCl_2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(0.3μmol/L)、环氧合酶抑制剂吲哚美辛(100μmol/L)、细胞外信号调节激酶ERK1/2抑制剂PD98059(10μmol/L)和氯通道阻滞剂尼氟灭酸(100μmol/L)分别使BaCl_2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,BaCl_2引起RCA收缩依赖于[Ca~(2+)]_i释放和[Ca~(2+)]_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。
In order to investigate the mechanism of contraction of rat coronary artery (RCA) caused by inward rectifier K ~ + channels (K_ (ir)) blocker BaCl_2, in vitro angiotensin II To observe the effects of RCA contraction induced by BaCl 2 on the intracellular Ca 2+ release and the intracellular Ca 2+ release of [Ca 2+] Dependence, and through the inhibitor experiment to explore its mechanism of action. The results showed that BaCl_2 (0.1-1.0 mmol / L) shrank the contraction of RCA in a concentration-dependent manner at rest (5.69 ± 1.07) m N, which was similar to that of KCl (60 mmol / L) The contraction induced by BaCl 2 in non-calcium solution accounted for 35.44 ± 6.72% of the total contraction and the re-calcium caused a further contraction of 64.56 ± 5.94%. The calcium channel blocker nifedipine (0.3μmol / L) The inhibitory effects of cyclooxygenase inhibitor indomethacin (100μmol / L), extracellular signal-regulated kinase ERK1 / 2 inhibitor PD98059 (10μmol / L) and chloride channel blocker niflumic acid (100μmol / L) (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). The above experimental results show that the RCA contraction induced by BaCl 2 is dependent on the release of [Ca 2+] i and the influx of [Ca 2 +] _o, suggesting that this process is related to the increase of prostaglandin synthesis, calcium channel and chloride Channel activation and ERK1 / 2 pathway.