Augmentation of NO-mediated vasodilation in metabolic acidosis
Augmentation of NO-mediated vasodilation in metabolic acidosis
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DOI：
10.1016/s0024-3205(02)01914-8
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发表时间：
2002-08-09
期刊：
影响因子：
6.1
通讯作者：
Muramatsu, I
中科院分区：
文献类型：
--
作者：
Hattori, K;Tsuchida, S;Muramatsu, I
酸血症时血管周围pH值的降低导致血管床对血管收缩剂的低反应性。在本研究中，我们研究了适度酸化对离体大鼠胸主动脉扩张反应的影响。乙酰胆碱产生内皮依赖性舒张苯肾上腺素预收缩的主动脉，这是显着增强酸化的Krebs-Henseleit溶液从pH 7.4至7.0。在内皮剥脱、苯肾上腺素收缩的主动脉中，观察到对NO供体（SNP、SIN-1、SNAP）、8-Br-cGMP和NS-1619（推定的K-Ca通道开放剂和/或Ca通道抑制剂）的舒张反应的类似增强。然而，罂粟碱诱导的松弛不受pH值的变化。在pH值7.4时，乙酰胆碱和SNP的松弛反应被Charybdotoxin（K-Ca通道抑制剂）而不是格列本脲（K-ATP通道抑制剂）部分抑制，而在pH值7.0时，由任何药物诱导的松弛不受K+通道抑制剂的影响。8-Br-cGMP或NS-1619引起的舒张作用不被Charybdotoxin或格列本脲抑制。酸化至pH 7.0增加cGMP生产响应乙酰胆碱在内皮完整的主动脉和SNP在内皮剥脱的主动脉。这些结果表明，适度酸化增强NO介导的舒张大鼠主动脉，可能是由于cGMP依赖性，但K+通道无关的舒张机制的增强。(C)2002年爱思唯尔科学公司All rights reserved.
Reduction of perivascular pH in acidemia produces hyporesponsiveness of vascular bed to vasoconstrictors. In the present study, we examined the effects of modest acidification on dilatory responses of isolated rat thoracic aorta. Acetylcholine produced endothelium-dependent relaxation in phenylephrine-precontracted aorta, which was markedly enhanced by acidification of Krebs-Henseleit solution from pH 7.4 to 7.0. A similar augmentation was observed in the relaxing responses to NO donors (SNP, SIN-1, SNAP), 8-Br-cGMP and NS-1619 (a putative K-Ca channel opener and/or Ca channel inhibitor) in endothelium-denuded, phenylephrine-contracted aorta. However, papaverine-induced relaxation was not affected by the change in pH. At pH 7.4, the relaxing responses to acetylcholine and SNP were partially inhibited by charybdotoxin (K-Ca channel inhibitor) but not glibenclamide (K-ATP channel inhibitor), while at pH 7.0 the relaxation induced by either drug was not affected by K+ channel inhibitors. Relaxation induced by 8-Br-cGMP or NS-1619 was not inhibited by charybdotoxin or glibenclamide. Acidification to pH 7.0 increased the cGMP production in response to acetylcholine in endothelium-intact aorta and to SNP in endothelium-denuded aorta. These results show that modest acidification augments NO-mediated relaxation in rat aorta, probably due to an enhancement of cGMP-dependent but K+ channel-unrelated relaxation mechanisms. (C) 2002 Elsevier Science Inc. All rights reserved.