Vasodilator responses to acetylcholine are not mediated by the activation of soluble guanylate cyclase or TRPV4 channels in the rat
Vasodilator responses to acetylcholine are not mediated by the activation of soluble guanylate cyclase or TRPV4 channels in the rat
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DOI：
10.1152/ajpheart.00978.2013
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发表时间：
2014-06-01
影响因子：
4.8
通讯作者：
Kadowitz, Philip J.
中科院分区：
文献类型：
--
作者：
Pankey, Edward A.;Kassan, Modar;Kadowitz, Philip J.
本文观察了可溶性鸟苷酸环化酶（sGC）激活抑制剂1H-[1，2，4]-恶二唑并[4，3-]喹喔啉-1-酮（ODQ）对大鼠肺和体血管床对一氧化氮（NO）供体乙酰胆碱（ACh）和缓激肽（BK）反应的影响。在这些研究中，以5 mg/kg的剂量iv给予ODQ减弱了对五种不同NO供体的血管舒张反应，而不抑制大鼠全身和肺血管床中对ACh和BK的反应。L-NAME或瞬时受体香草酸4型（TRPV 4）拮抗剂GSK-2193874（其减弱TRPV 4激动剂GSK-1016790 A的血管扩张反应）不抑制ACh的血管扩张反应。ODQ没有抑制血管扩张剂的反应，据报道，在一氧化氮非依赖性的方式或血管收缩剂，和ODQ没有增加血液高铁血红蛋白水平，表明脱靶效应是最小的。这些结果表明，在抑制NO供体的剂量下，介导的反应并不改变肺和全身血管床对ACh的血管舒张反应，也不改变对BK的全身血管舒张反应。目前的结果表明，ACh引起的肺和全身动脉压降低不是由sGC或TRPV 4通道的激活介导的，ODQ可用于研究ACh的作用。在大鼠中介导血管舒张反应的sGC活化。
The effects of 1H-[1,2,4]-oxadizaolo[4,3-]quinoxaline-1-one (ODQ), an inhibitor of the activation of soluble guanylate cyclase (sGC) on responses to NO donors acetylcholine (ACh) and bradykinin (BK) were investigated in the pulmonary and systemic vascular beds of the rat. In these studies the administration of ODQ in a dose of 5 mg/kg iv attenuated vasodilator responses to five different NO donors without inhibiting responses to ACh and BK in the systemic and pulmonary vascular beds of the rat. Vasodilator responses to ACh were not inhibited by L-NAME or the transient receptor vanilloid type 4 (TRPV4) antagonist GSK-2193874, which attenuated vasodilator responses to the TRPV4 agonist GSK-1016790A. ODQ did not inhibit vasodilator responses to agents reported to act in an NO-independent manner or to vasoconstrictor agents, and ODQ did not increase blood methemoglobin levels, suggesting that off target effects were minimal. These results show that ODQ in a dose that inhibited NO donor-mediated responses did not alter vasodilator responses to ACh in the pulmonary and systemic vascular beds and did not alter systemic vasodilator responses to BK. The present results indicate that decreases in pulmonary and systemic arterial pressures in response to ACh are not mediated by the activation of sGC or TRPV4 channels and that ODQ can be used to study the role of the activation of sGC in mediating vasodilator responses in the rat.