RELAXATION AND DECREASE IN [CA2+](I) BY HYDROCHLOROTHIAZIDE IN GUINEA-PIG ISOLATED MESENTERIC-ARTERIES
RELAXATION AND DECREASE IN [CA2+](I) BY HYDROCHLOROTHIAZIDE IN GUINEA-PIG ISOLATED MESENTERIC-ARTERIES
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DOI：
10.1111/j.1476-5381.1995.tb17195.x
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发表时间：
1995-02-01
影响因子：
7.3
通讯作者：
HUGHES, AD
中科院分区：
文献类型：
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作者：
PICKKERS, P;HUGHES, AD
1我们检测了噻嗪类利尿剂氢氯噻嗪对豚鼠肠系膜动脉细胞内钙浓度（[Ca 2 +]（i））和张力的影响。将血管固定在微血管肌描记器上，并加载Ca 2+敏感性荧光染料Fura-2.2氢氯噻嗪，引起去甲肾上腺素预收缩动脉舒张，与[Ca 2 +]下降相关（i）。用氢氯噻嗪预孵育的动脉抑制了去甲肾上腺素引起的收缩和[Ca 2 +]（i）升高。当去极化钾溶液和去甲肾上腺素联合升高时，氢氯噻嗪不影响张力和[Ca 2 +]（i）。3氢氯噻嗪诱导的血管舒张和[Ca 2 +]（i）的降低被大电导Ca 2+激活K通道阻滞剂Charybdotoxin消除。4在无Ca 2+的生理盐溶液中，咖啡因引起的[Ca 2 +]（i）升高，推测反映了细胞内钙库的钙释放，并没有被氢氯噻嗪预孵育所改变。5在去极化条件下，氢氯噻嗪没有改变细胞外钙浓度和[Ca 2 +]（i）之间的关系;但是，在此情况下，氢氯噻嗪导致[Ca 2 +]（i）升高引起的收缩略有减少这表明氢氯噻嗪可能会导致收缩机制的轻微脱敏。6这些发现表明，氢氯噻嗪打开Ca 2 +-激活K通道，导致超极化和随后关闭电压操纵的钙通道。其结果是细胞外Ca 2+内流受损，[Ca 2 +]（i）减少和血管舒张。
1 We examined the effect of the thiazide diuretic, hydrochlorothiazide, on intracellular calcium concentration ([Ca2+](i)) and tone in guinea-pig mesentery arteries. Vessels were mounted on a microvascular myograph and loaded with the Ca2+-sensitive fluorescent dye, Fura-2.2 Hydrochlorothiazide caused relaxation of noradrenaline-precontracted arteries associated with a fall in [Ca2+](i). Preincubation of arteries with hydrochlorothiazide inhibited, both contraction and rise in [Ca2+](i) in response to noradrenaline. Hydrochlorothiazide did not affect tone and [Ca2+](i) when this was elevated by a combination of depolarizing potassium solution and noradrenaline.3 Hydrochlorothiazide-induced vasorelaxation and decrease of [Ca2+](i) was abolished by charybdotoxin, a blocker of large conductance Ca2+-activated K channels.4 The rise in [Ca2+](i) elicited by caffeine in Ca2+-free physiological salt solution, and presumably reflecting Ca2+ release from intracellular stores, was not altered by preincubation with hydrochlorothiazide.5 Under depolarizing conditions hydrochlorothiazide did not alter the relationship between the extracellular concentration of Ca2+ and [Ca2+](i); however, hydrochlorothiazide caused a small reduction in the contraction produced for a given rise in [Ca2+](i) suggesting hydrochlorothiazide may cause a slight desensitization of the contractile machinery.6 These findings suggest that hydrochlorothiazide opens Ca2+-activated K channels leading to hyperpolarization and consequent closing of voltage-operated calcium channels. The result of this is an impaired influx of extracellular Ca2+, a decrease in [Ca2+](i) and vasorelaxation.