Wagner R S, Weare C, Jin N, Mohler E R, Rhoades R A
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202, USA.
Prostaglandins. 1997 Aug;54(2):581-99. doi: 10.1016/s0090-6980(97)00127-5.
One of the most abundant F2 isoprostanes formed under pathological conditions is 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha), a potent vasoconstrictor. The purpose of this study was to determine the signal transduction events initiated by 8-epi-PGF2 alpha-induced vasoconstriction. Isolated arterial rings from male Sprague-Dawley rats were suspended in tissue baths containing Krebs-Henseleit salt solution, stretched to optimal resting tension and stimulated. 8-epi-PGF2 alpha induced concentration-dependent contractions in pulmonary arteries (EC50: 7.7 +/- 2.1 microM; n = 3) and aortas (EC50: 0.9 +/- 0.1 microM; n = 4) which were blocked by the TXA2 receptor antagonists SQ29548, L657925 and L657926. The contractile response to 8-epi-PGF2 alpha was significantly (*p < 0.05; n = 4) diminished by: 1) indomethacin and ibuprofen; 2) Ca++ free media; 3) verapamil, a voltage gated Ca++ channel blocker; 4) flunarizine, a T-type Ca++ channel blocker; and 5) calphostin C, a protein kinase C inhibitor. These data suggest that the contractile response to 8-epi-PGF2 alpha is: 1) mediated via activation of TXA2 receptors; 2) partially dependent on the synthesis and release of other cyclooxygenase derived products; 3) dependent on an influx of extracellular Ca++ possibly via Ca++ channels; and 4) may be PKC dependent.
在病理条件下形成的最丰富的F2异前列腺素之一是8-表-前列腺素F2α（8-epi-PGF2α），一种强效血管收缩剂。本研究的目的是确定由8-epi-PGF2α诱导的血管收缩引发的信号转导事件。将来自雄性Sprague-Dawley大鼠的离体动脉环悬挂在含有Krebs-Henseleit盐溶液的组织浴中，拉伸至最佳静息张力并进行刺激。8-epi-PGF2α在肺动脉（EC50：7.7±2.1 microM；n = 3）和主动脉（EC50：0.9±0.1 microM；n = 4）中诱导浓度依赖性收缩，这些收缩被TXA2受体拮抗剂SQ29548、L657925和L657926阻断。对8-epi-PGF2α的收缩反应被以下因素显著减弱（*p < 0.05；n = 4）：1）吲哚美辛和布洛芬；2）无钙培养基；3）维拉帕米，一种电压门控钙通道阻滞剂；4）氟桂利嗪，一种T型钙通道阻滞剂；5）钙调蛋白C，一种蛋白激酶C抑制剂。这些数据表明，对8-epi-PGF2α的收缩反应：1）通过TXA2受体的激活介导；2）部分依赖于其他环氧化酶衍生产物的合成和释放；3）依赖于细胞外钙可能通过钙通道的内流；4）可能依赖于蛋白激酶C。
