Kato Kenichi, Betts Luisa C, Kozlowski Roland Z, Kitamura Kenji
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Sawara, Japan.
J Cardiovasc Pharmacol. 2006 Mar;47(3):476-86. doi: 10.1097/01.fjc.0000211730.69045.b7.
We investigated the difference in the characteristics of endothelin-1 (ET-1)-induced contraction and the responses of intracellular Ca(2+) concentration (Ca(2+)) between rat small pulmonary artery and renal artery. ET-1 (30 nM) failed to elicit any contraction in renal arteries pretreated with 3 microM BQ-123, an ETA blocker. However, in the pulmonary artery a combination of BQ-123 and BQ-788, an ETB blocker (5 microM each), only partially inhibited the ET-1-induced contraction (by 25%). To focus on the ETA receptor, in the presence of 5 microM BQ-788, nitric oxide donors (sodium nitroprusside and (+/-)-S-nitroso-N-acetylpenicillamine) and forskolin reduced both the ET-1-induced contraction and increase in Ca(2+) in both pulmonary and renal arteries. However, the effects were stronger in the renal than in the pulmonary artery. ET-1-induced increase in Ca(2+) was only partially attenuated by 10 microM verapamil (to 81% of control) in pulmonary arteries but was reduced to 56.1% of control in renal arteries. Our results provide evidence that ET-1 may activate ET receptor(s) insensitive to both BQ-123 and BQ-788 in rat small pulmonary artery, at least under these conditions. Furthermore, the effects of relaxants such as L-type Ca(2+) channel blocker and nitric oxide donors on the ET-1-induced contraction were studied.
我们研究了大鼠小肺动脉和肾动脉中内皮素 -1（ET-1）诱导收缩的特征以及细胞内钙离子浓度（Ca(2+)）反应的差异。ETA 受体阻断剂 3 microM BQ-123 预处理的肾动脉中，ET-1（30 nM）未能引发任何收缩。然而，在肺动脉中，ETB 受体阻断剂 BQ-788（各 5 microM）与 BQ-123 的组合仅部分抑制了 ET-1 诱导的收缩（25%）。为聚焦于 ETA 受体，在存在 5 microM BQ-788 的情况下，一氧化氮供体（硝普钠和（±）-S-亚硝基-N-乙酰青霉胺）和福斯可林降低了肺动脉和肾动脉中 ET-1 诱导的收缩以及 Ca(2+) 的增加。然而，肾动脉中的作用比肺动脉中更强。ET-1 诱导的肺动脉中 Ca(2+) 的增加仅被 10 microM 维拉帕米部分减弱（降至对照的 81%），而在肾动脉中则降至对照的 56.1%。我们的结果提供了证据，表明至少在这些条件下，ET-1 可能激活大鼠小肺动脉中对 BQ-123 和 BQ-788 均不敏感的 ET 受体。此外，还研究了 L 型 Ca(2+)通道阻断剂和一氧化氮供体等松弛剂对 ET-1 诱导收缩的影响。
