Mechanisms underlying ATP-induced endothelium-dependent contractions in the SHR aorta
Mechanisms underlying ATP-induced endothelium-dependent contractions in the SHR aorta
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DOI：
10.1016/j.ejphar.2006.10.050
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发表时间：
2007-02-05
影响因子：
5
通讯作者：
Feletou, Michel
中科院分区：
文献类型：
--
作者：
Gluais, Pascale;Vanhoutte, Paul M.;Feletou, Michel
在成年自发性高血压（SHR）和Wistar-Kyoto（WKY）大鼠中，乙酰胆碱、钙离子载体A23187和ATP释放内皮源性收缩因子（EDCF）、环氧合酶（考克斯）衍生物，激活血管平滑肌上的血栓素-内过氧化物（TP）受体。乙酰胆碱释放的EDCF被鉴定为前列环素和前列腺素（PG）H-2，而在对A 23187血栓烷A（2）的反应中，沿着另外两种肾上腺素，有助于内皮依赖性收缩。本研究的目的是鉴定ATR所产生的EDCF。在WKY大鼠和SHR的离体主动脉环上，测量了等长张力和Eschlandin的释放。ATP以类似的方式在WKY大鼠和SHR的主动脉中产生前列环素、血栓素A（2）和PGE（2）的内皮依赖性释放（PGI（2）>> TXA（2）>= PGE（2）> PGF（2 α））。在自发性高血压大鼠心房肌中，ATP引起的血栓素A（2）释放量明显大于乙酰胆碱，而前列环素引起的血栓素A（2）释放量明显小于乙酰胆碱。用吲哚美辛抑制环氧合酶可阻止三尖杉酯碱的释放和内皮依赖性收缩的发生。血栓素合成酶抑制剂达唑昔本选择性地消除ATP依赖的血栓素A的产生（2），并部分抑制相应的内皮依赖性收缩。U 51605是一种非选择性的PGI-synthase抑制剂，可减少ATP引起的前列环素的释放，但同时诱导PGE（2）和PGF（2 α）的产生增加，提示PGH（2）-溢出，这与内皮依赖性收缩的增强有关。因此，在SHR的主动脉中，ATP引起的内皮依赖性收缩涉及血栓素A（2）和前列环素的释放，可能有PGH（2）的贡献。(c)2006 Elsevier B. V.保留所有权利。
In mature spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats, acetylcholine, the calcium ionophore A 23187 and ATP release endothelium-derived contracting factor (EDCF), cyclooxygenase (COX) derivatives that activate thromboxane-endoperoxide (TP) receptors on vascular smooth muscle. The EDCFs released by acetylcholine have been identified as prostacyclin and prostaglandin (PG) H-2 while in response to A 23187 thromboxane A(2), along with the two other prostaglandins, contributes to the endothelium-dependent contractions. The purpose of the present study was to identify the EDCFs produced by ATR Isometric tension and the release of prostaglandins were measured in isolated aortic rings of WKY rats and SHR. ATP produced the endothelium-dependent release of prostacyclin, thromboxane A(2) and PGE(2) (PGI(2) >> TXA(2) >= PGE(2) > PGF(2 alpha)) in a similar manner in aorta from WKY rats and SHR. In SHR aortas, the release of thromboxane A(2) was significantly larger in response to ATP than to acetylcholine while that to prostacyclin was significantly smaller. The inhibition of cyclooxygenase with indomethacin prevented the release of prostaglandins and the occurrence of endothelium-dependent contractions. The thromboxane synthase inhibitor dazoxiben selectively abolished the ATP-dependent production of thromboxane A(2) and partially inhibited the corresponding endothelium-dependent contractions. U 51605, a non-selective inhibitor of PGI-synthase, reduced the release of prostacyclin elicited by ATP but induced a parallel increase in the production of PGE(2) and PGF(2 alpha), suggestive of a PGH(2)-spillover, which was associated with the enhancement of the endothelium-dependent contractions. Thus, in the aorta of SHR, endothelium-dependent contractions elicited by ATP involve the release of thromboxane A(2) and prostacyclin with a possible contribution of PGH(2). (c) 2006 Elsevier B.V. All rights reserved.