酸中毒致大鼠离体冠状动脉收缩的机制  

Mechanisms underlying contraction of rat isolated coronary artery induced by acidosis

作　　者：贺泽芳[1] 侯晓敏[1] 杨蓉[1] 范芳文[1] 郭鹏美 刘宇[1] 张明升[1] 

机构地区：[1]山西医科大学药理学教研室,山西太原030001

出　　处：《中国病理生理杂志》2017年第5期838-842,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81603111);山西省生物优势学科基金;山西医科大学博士启动基金(No.03201510)

摘　　要：目的:探讨细胞外酸中毒(pH_(ex)6.8)致大鼠离体冠状动脉(RCA)收缩的机制。方法:采用离体微血管张力法,通过观察Na^+-H^+交换体1(NHE-1)选择性抑制剂cariporide(HOE-642)或Na^+-HCO_3^-共同转运体(NBC)抑制剂S0859预孵对pH_(ex)6.8所致RCA收缩的影响,探讨酸碱转运体在酸中毒收缩RCA中的作用;通过观察氯通道抑制剂NPPB和尼氟酸(NFA)预孵及细胞外去除氯离子对pH_(ex)6.8所致RCA收缩的影响,探讨氯离子通道在酸中毒收缩RCA中的作用。结果:pH_(ex)6.8引起RCA静息张力升高,最大张力为(3.90±0.95)mN。30μmol/L HOE-642和100μmol/L S0859均抑制pH_(ex)6.8引起的RCA收缩(P<0.01)。NPPB和NFA均呈浓度依赖性地抑制pH_(ex)6.8引起的RCA收缩和KCl(60 mmol/L)引起的收缩。100μmol/L的NPPB和NFA均抑制U46619(1μmol/L)引起的RCA收缩(P<0.01)。等摩尔NaBr代替细胞外液中NaCl后,几乎完全抑制pH_(ex)6.8引起的RCA收缩(P<0.01),但是对KCl(60 mmol/L)或U46619(1μmol/L)引起的RCA收缩无显著影响。结论:细胞外液酸化所致的RCA收缩与激活NHE-1和NBC及促进氯离子跨细胞膜运动有关。AIM： To explore the mechanisms underlying contraction induced by extracelluar acidosis （pHex6.8） in rat isolated coronary artery （RCA）.METHODS： Using the microvessel tension recorder system, the effects of acid-base transporters on RCA contraction induced by pHex6.8 were explored by applying the selective pharmacological inhibitors of Na＋-H＋ exchanger 1 （NHE-1） and Na＋-HCO3- cotransporter （NBC）, HOE-642 and S0859, respectively. The effects of chloride channel on RCA contraction induced by pHex6.8 were explored by applying the inhibitors of chloride channel （NPPB and NFA）, and by replacing the extracellular NaCl with equimolar NaBr.RESULTS： pHex6.8 augmented the resting tension of RCA, and the maximum contraction was （3.90±0.95） mN. HOE-642 at 30 μmol/L and S0859 at 100 μmol/L both inhibited the contraction of RCA induced by pHex6.8 （P〈0.01）. NPPB and NFA both inhibited the contraction of RCA induced by pHex6.8 or KCl （60 mmol/L） in a concentration-dependent manner. NPPB and NFA （100 μmol/L） both inhibited the contraction of RCA induced by U46619 （1 μmol/L）. Replacing the extracellular NaCl with equimolar NaBr almost completely inhibited RCA contraction induced by pHex6.8 （P〈0.01）, but had no obvious effect on the contraction induced by KCl （60 mmol/L） or U46619 （1 μmol/L）.CONCLUSION： Extracellular acidosis-induced contraction in RCA may be related to the activated NHE-1 and NBC, and it may be also related to the enhanced chloride transport across the membrane.

关 键 词：酸中毒 冠状动脉 Na^+-H^+交换体 Na^+-HCO_3^-共同转运体 氯离子通道 

分 类 号：R363[医药卫生—病理学]