InSHR aorta, calcium ionophore A-23187 releases prostacyclin and thromboxane A2 as endothelium-derived contracting factors
InSHR aorta, calcium ionophore A-23187 releases prostacyclin and thromboxane A2 as endothelium-derived contracting factors
复制标题
DOI：
10.1152/ajpheart.01115.2005
复制
发表时间：
2006-11-01
影响因子：
4.8
通讯作者：
Feletou, Michel
中科院分区：
文献类型：
--
作者：
Gluais, Pascale;Paysant, Jerome;Feletou, Michel
在成熟自发性高血压大鼠 (SHR) 和 Wistar-Kyoto 大鼠 (WKY) 中，乙酰胆碱和钙离子载体 A-23187 释放内皮衍生收缩因子 (EDCF)、环氧合酶衍生物，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 最有可能是前列环素和前列腺素 (PG)H-2，而 A-23187 释放的 EDCF 仍有待鉴定。在 WKY 和 SHR 的离体主动脉环中测量等长张力和 PG 释放。 A-23187 引起前列环素、血栓素 A(2)、PGF(2 α)、PGE(2) 和可能的 PGH(2) 的内皮依赖性释放（PGI(2) >> 血栓素 A(2) = PGF(2 α) = PGE(2)）。在 SHR 主动脉中，A-23187 释放的前列环素和血栓素 A(2) 明显多于乙酰胆碱。响应钙离子载体，SHR 主动脉中血栓素 A(2) 的释放量显着高于 WKY 的主动脉。在这两种大鼠中，抑制 cyclooxygenase-1 可以阻止 PG 的释放和内皮依赖性收缩的发生。 Dazoxiben 是一种血栓素合酶抑制剂，可消除 A-23187 依赖性血栓素 A(2) 的产生，并抑制大约一半的内皮依赖性收缩。 U-51605 是一种 PGI 合酶抑制剂，可减少 A-23187 引起的前列环素的释放，但诱导 PGE(2) 和 PGF(2 α) 的产生平行增加，提示 PGH(2) 溢出，这与内皮依赖性收缩的增强有关。这些结果表明，在 SHR 和 WKY 的主动脉中，A-23187 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，最有可能伴随着 PGH(2) 的贡献。
In mature spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), acetylcholine and the calcium ionophore A-23187 release endothelium-derived contracting factors (EDCFs), cyclooxygenase derivatives that activate thromboxane-endoperoxide (TP) receptors on vascular smooth muscle. The EDCFs released by acetylcholine are most likely prostacyclin and prostaglandin (PG)H-2, whereas those released by A-23187 remain to be identified. Isometric tension and the release of PGs were measured in rings of isolated aortas of WKY and SHR. A-23187 evoked the endothelium-dependent release of prostacyclin, thromboxane A(2), PGF(2 alpha), PGE(2), and possibly PGH(2) (PGI(2) >> thromboxane A(2) = PGF(2 alpha) = PGE(2)). In SHR aortas, the release of prostacyclin and thromboxane A(2) was significantly larger in response to A-23187 than to acetylcholine. In response to the calcium ionophore, the release of thromboxane A(2) was significantly larger in aortas of SHR than in those of WKY. In both strains of rat, the inhibition of cyclooxygenase-1 prevented the release of PGs and the occurrence of endothelium-dependent contractions. Dazoxiben, the thromboxane synthase inhibitor, abolished the A-23187-dependent production of thromboxane A(2) and inhibited by approximately one-half the endothelium-dependent contractions. U-51605, an inhibitor of PGI synthase, reduced the release of prostacyclin elicited by A-23187 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. These results indicate that in the aorta of SHR and WKY, the endothelium-dependent contractions elicited by A-23187 involve the release of thromboxane A(2) and prostacyclin with a most likely concomitant contribution of PGH(2).