• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Mechanisms of endothelin-1-induced contraction in pulmonary arteries from chronically hypoxic rats.
【24h】

Mechanisms of endothelin-1-induced contraction in pulmonary arteries from chronically hypoxic rats.

机译：内皮素-1诱导的慢性低氧大鼠肺动脉收缩机制。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Endothelin-1 (ET-1), a potent vasoconstrictor, is believed to contribute to the pathogenesis of hypoxic pulmonary hypertension. Previously we demonstrated that contraction induced by ET-1 in intrapulmonary arteries (IPA) from chronically hypoxic (CH) rats occurred independently of changes in intracellular Ca2+ concentration ([Ca2+]i), suggesting that ET-1 increased Ca2+ sensitivity. The mechanisms underlying this effect are unclear but could involve the activation of myosin light chain kinase, Rho kinase, PKC, or tyrosine kinases (TKs), including those from the Src family. In this study, we examined the effect of pharmacological inhibitors of these kinases on maximum tension generated by IPA from CH rats (10% O2 for 21 days) in response to ET-1. Experiments were conducted in the presence of nifedipine, an L-type Ca2+ channel blocker, to isolate the component of contraction that occurred without a change in [Ca2+]i. The mean change in tension caused by ET-1 (10(-8) M) expressed as a percent of the maximum response to KCl was 184.0+/-39.0%. This response was markedly inhibited by the Rho kinase inhibitors Y-27632 and HA-1077 and the TK inhibitors genistein, tyrphostin A23, and PP2. In contrast, staurosporine and GF-109203X, inhibitors of PKC, had no significant inhibitory effect on the tension generated in response to ET-1. We conclude that the component of ET-1-induced contraction that occurs without a change in [Ca2+]i in IPA from CH rats requires activation of Rho kinase and TKs, but not PKC.
机译：内皮素-1（ET-1）是一种有效的血管收缩剂，被认为有助于低氧性肺动脉高压的发病机理。先前我们证明了由ET-1引起的慢性低氧（CH）大鼠的肺内动脉（IPA）的收缩独立于细胞内Ca2 +浓度（[Ca2 +] i）的变化而发生，这表明ET-1增加了Ca2 +的敏感性。该作用的机制尚不清楚，但可能涉及肌球蛋白轻链激酶，Rho激酶，PKC或酪氨酸激酶（TK）的激活，包括来自Src家族的那些。在这项研究中，我们检查了这些激酶的药理抑制剂对CH大鼠IPA产生的最大张力的反应（10％O2，持续21天），以响应ET-1。在硝苯地平（一种L型Ca2 +通道阻滞剂）的存在下进行了实验，以分离出在[Ca2 +] i不变的情况下发生的收缩成分。由ET-1（10（-8）M）引起的平均张力变化表示为对KCl的最大反应的百分比为184.0 +/- 39.0％。 Rho激酶抑制剂Y-27632和HA-1077以及TK抑制剂染料木黄酮，酪氨酸酪蛋白A23和PP2显着抑制了该反应。相反，星形孢菌素和GF-109203X（PKC抑制剂）对响应ET-1产生的张力没有明显的抑制作用。我们得出的结论是，由CH大鼠IPA中的ET-1-诱导的收缩发生而无需改变[Ca2 +] i，需要激活Rho激酶和TKs，而不激活PKC。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号