Analysis of responses to endothelins 1, 2, and 3 and sarafotoxin 6b in airways of the cat.
Analysis of responses to endothelins 1, 2, and 3 and sarafotoxin 6b in airways of the cat.
复制标题
猫气道内皮素 1、2、3 和 sarafotoxin 6b 的反应分析。
DOI：
10.1152/jappl.1991.71.1.243
复制
发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Kadowitz,PJ
中科院分区：
文献类型：
--
作者：
Dyson,MC;Kadowitz,PJ
在麻痹、麻醉、机械通气的猫上研究了气道对内皮素（ET）1、ET-2、ET-3和Sarafotoxin 6 b（S6 b）的反应。静脉注射ET-1（0.11nmol/kg）可使肺动脉压（Ptp）和肺阻力（RL）升高，动态顺应性（Cdyn）降低，并呈剂量相关性。环氧合酶抑制剂甲氨蝶呤钠和血栓素受体阻断剂SKF 96148可显著降低气道对ET-1的反应。在相对支气管收缩活性方面，血栓烷模拟物U-46619在增加Ptp方面比ET-1的摩尔效力高3倍。ET-1和ET-3具有相似的支气管收缩活性，并且这些肽的效力低于ET-2和S6 b。对ET-2、ET-3和S6 b的支气管收缩反应也被甲氨蝶呤和血栓素受体阻断剂显著降低。ET-1前体ET-1-（1-38）（大ET-1）引起Ptp、RL和主动脉压（PAO）的显著缓慢发展的增加和Cdyn的降低，而单环ET-1类似物和ET-1-（16-21）六肽片段在气道中几乎没有或没有活性。目前的数据表明，ET-1，ET-2，ET-3，和S6 b具有显着的支气管收缩活性的猫和响应部分依赖于花生四烯酸的释放和血栓烷A2的形成。这些数据还表明，大ET-1在猫中转化为成熟肽，ET-1-（16-21）六肽片段和单环ET-1类似物在麻醉猫中几乎没有支气管收缩活性。
Airway responses to endothelin (ET) 1, ET-2, ET-3, and sarafotoxin 6b (S6b) were investigated in paralyzed, anesthetized, mechanically ventilated cats. Intravenous injections of ET-1 (0.11 nmol/kg) increased transpulmonary pressure (Ptp) and lung resistance (RL) and decreased dynamic compliance (Cdyn) in a dose-related manner. Airway responses to ET-1 were decreased significantly by sodium meclofenamate, a cyclooxygenase inhibitor, and by SKF 96148, a thromboxane receptor blocking agent. In terms of relative bronchoconstrictor activity, the thromboxane mimic, U-46619, was threefold more potent than ET-1 on a molar basis in increasing Ptp. ET-1 and ET-3 had similar bronchoconstrictor activity, and these peptides were less potent than ET-2 and S6b. Bronchoconstrictor responses to ET-2, ET-3, and S6b were also decreased significantly by meclofenamate and by thromboxane receptor blocking agents. The ET-1 precursor ET-1-(1–38) (big ET-1) caused a significant slowly developing increase in Ptp, RL, and aortic pressure (PAO) and a decrease in Cdyn, whereas a monocyclic ET-1 analogue and ET-1-(16–21) hexapeptide fragment had little or no activity in the airways. The present data indicate that ET-1, ET-2, ET-3, and S6b have significant bronchoconstrictor activity in the cat and that responses are dependent in part on the release of arachidonic acid and the formation of thromboxane A2. These data also suggest that big ET-1 is converted into a mature peptide in the cat and that ET-1-(16–21) hexapeptide fragment and a monocyclic ET-1 analogue have little if any bronchoconstrictor activity in the anesthetized cat.