Ito T, Kato T, Iwama Y, Muramatsu M, Okumura K, Hashimoto H, Satake T, Ogawa K
2nd Department of Internal Medicine, Nagoya University School of Medicine.
Kokyu To Junkan. 1990 Oct;38(10):1001-7.
The present experiment was performed to identify endothelium-derived contracting factor produced by acetylcholine stimulation in the aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The rings of the thoracic aorta were obtained from age-matched SHR and WKY, and changes in isometric tension were recorded. The relaxant responses to acetylcholine in the rings from SHR were significantly weaker than those obtained in WKY. The relaxant responses to acetylcholine were significantly enhanced by pretreatment with a cyclooxygenase-inhibitor (indomethacin) or thromboxane A2/prostaglandin H2 receptor antagonist (ONO-3708) both in the SHR and WKY rings. A thromboxane A2 synthetase inhibitor (OKY-046) did not affect the acetylcholine-induced relaxation in the rings from SHR or WKY. In the organ bath solution, following acetylcholine stimulation, prostaglandin E2 and 6-keto-prostaglandin F1 alpha concentrations increased, but prostaglandin F2 alpha and thromboxane B2 concentrations did not increase. Exogenous prostaglandin H2, a stable analogue of thromboxane A2 (STA2) and prostaglandin F2 alpha induced contractions of the SHR rings at a lower concentration than prostaglandin E2, prostaglandin D2 and prostaglandin I2. These contractile responses to various prostaglandins were markedly inhibited by pretreatment with ONO-3708. A prostacyclin synthetase inhibitor did not affect the relaxant responses to acetylcholine in the SHR rings. These results show that endothelium-derived contracting factor is produced and released by acetylcholine stimulation not only in the aorta of SHR but also in that of WKY. The results also suggest that prostaglandin H2, a precursor of the released prostaglandins, is a strong candidate for endothelium-derived contracting factor produced by acetylcholine stimulation.
本实验旨在鉴定自发性高血压大鼠（SHR）和正常血压的Wistar-Kyoto大鼠（WKY）主动脉中由乙酰胆碱刺激产生的内皮源性收缩因子。从年龄匹配的SHR和WKY获取胸主动脉环，并记录等长张力的变化。SHR主动脉环对乙酰胆碱的舒张反应明显弱于WKY的。在SHR和WKY的主动脉环中，用环氧化酶抑制剂（吲哚美辛）或血栓素A2/前列腺素H2受体拮抗剂（ONO-3708）预处理后，对乙酰胆碱的舒张反应均显著增强。血栓素A2合成酶抑制剂（OKY-046）不影响SHR或WKY主动脉环中乙酰胆碱诱导的舒张。在器官浴液中，乙酰胆碱刺激后，前列腺素E2和6-酮-前列腺素F1α浓度升高，但前列腺素F2α和血栓素B2浓度未升高。外源性前列腺素H2、血栓素A2的稳定类似物（STA2）和前列腺素F2α在比前列腺素E2、前列腺素D2和前列腺素I2更低的浓度下诱导SHR主动脉环收缩。用ONO-3708预处理可显著抑制对各种前列腺素的这些收缩反应。前列环素合成酶抑制剂不影响SHR主动脉环中对乙酰胆碱的舒张反应。这些结果表明，乙酰胆碱刺激不仅在SHR主动脉中，而且在WKY主动脉中都会产生并释放内皮源性收缩因子。结果还表明，释放的前列腺素的前体前列腺素H2是乙酰胆碱刺激产生的内皮源性收缩因子的有力候选者。
