Acidosis induces relaxation mediated by nitric oxide and potassium channels in rat thoracic aorta
Acidosis induces relaxation mediated by nitric oxide and potassium channels in rat thoracic aorta
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DOI：
10.1016/j.ejphar.2011.01.053
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发表时间：
2011-04-10
影响因子：
5
通讯作者：
Evora, Paulo R. B.
中科院分区：
文献类型：
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作者：
Celotto, Andrea C.;Restini, Carolina B. A.;Evora, Paulo R. B.
我们研究了细胞外酸化促进大鼠胸主动脉舒张的机制。在用苯丙氨酸（Phe，10（-6）M）或KCl（45 mM）预收缩的主动脉环中测量对HCl诱导的细胞外酸化（7.4至6.5）的舒张反应。在存在或不存在吲哚美辛（10（-5）M）、L-NAME（10（-4）M）、apamin（10（-6）M）和格列本脲（10（-5）M）的情况下，在内皮完整和剥脱的环中进行血管反应性实验。细胞外酸中毒（pH 7.0和6.5）对一氧化氮（NO）的生产的影响进行了评价，在分离的内皮细胞加载二氨基荧光素-FM二乙酸酯（DAF-FM DA，5 μ M）。细胞外酸中毒未能引起KCl预收缩的主动脉环的血管张力的任何变化，然而，它引起了与Phe预收缩的环的内皮依赖性和非依赖性舒张。L-NAME、apamin和格列本脲可抑制这种酸中毒诱导的舒张，但吲哚美辛不能抑制。酸中毒（pH 7.0和6.5）也促进了分离的内皮细胞的NO产生的时间依赖性增加。这些结果表明，细胞外酸中毒促进血管舒张由NO，K-ATP和SKCa，并可能其他K+通道介导的离体大鼠胸主动脉。(C)2011爱思唯尔有限公司版权所有。
We investigated the mechanism by which extracellular acidification promotes relaxation in rat thoracic aorta. The relaxation response to HCl-induced extracellular acidification (7.4 to 6.5) was measured in aortic rings pre-contracted with phenylephrine (Phe, 10(-6) M) or KCl (45 mM). The vascular reactivity experiments were performed in endothelium-intact and denuded rings, in the presence or absence of indomethacin (10(-5) M), L-NAME (10(-4) M), apamin (10(-6) M), and glibenclamide (10(-5) M). The effect of extracellular acidosis (pH 7.0 and 6.5) on nitric oxide (NO) production was evaluated in isolated endothelial cells loaded with diaminofluorescein-FM diacetate (DAF-FM DA, 5 mu M). The extracellular acidosis failed to induce any changes in the vascular tone of aortic rings pre-contracted with KCl, however, it caused endothelium-dependent and independent relaxation in rings pre-contracted with Phe. This acidosis induced-relaxation was inhibited by L-NAME, apamin, and glibenclamide, but not by indomethacin. The acidosis (pH 7.0 and 6.5) also promoted a time-dependent increase in the NO production by the isolated endothelial cells. These results suggest that extracellular acidosis promotes vasodilation mediated by NO, K-ATP and SKCa, and maybe other K+ channels in isolated rat thoracic aorta. (C) 2011 Elsevier B.V. All rights reserved.