Ishikawa M, Namiki A
Third Department of Internal Medicine, Toho University School of Medicine, Ohashi Hospital, Japan.
Heart Vessels. 1994;9(1):14-8. doi: 10.1007/BF01744491.
The vascular contractile mechanism of prostacyclin (PGI2) was investigated using beraprost sodium (BPS), a stable PGI2 analog. Ring strips without endothelium isolated from canine femoral veins and arteries were used. BPS induced a dose-dependent contraction without precontraction and after precontraction with norepinephrine (NE) or 60 mM K+ in the veins. In contrast, BPS induced a dose-dependent relaxation after precontraction with U46619, a thromboxane A2 (TXA2) analog, or prostaglandin F2 alpha (PGF2 alpha) in the veins. In the arteries, BPS induced contraction at higher concentrations after precontraction with NE. However, BPS relaxed arteries dose-dependently after precontraction with PGF2 alpha. By pretreatment with 13-azaprostanoic acid (13-APA), a TXA2/endoperoxide receptor antagonist, the dose-response curve of BPS in the veins was shifted to the right. Schild plot analysis resulted in a linear regression with a slope of 0.86 +/- 0.13, which was not significantly different from unity, and the pA2 value for 13-APA against BPS was 7.10 +/- 0.06. By pretreatment with BPS, the dose-response curve of U46619 in the veins was shifted to the right. Kaumann plot analysis resulted in a linear regression with a slope of 0.89 +/- 0.09, which was not significantly different from unity, and the pA2 value for BPS against U46619 was 5.68 +/- 0.04. These findings indicate that BPS is a partial agonist for the TXA2/endoperoxide receptors.
使用稳定的前列环素（PGI2）类似物贝拉前列腺素钠（BPS）研究了前列环素（PGI2）的血管收缩机制。使用从犬股静脉和动脉分离的无内皮环条。在静脉中，BPS在无预收缩以及用去甲肾上腺素（NE）或60 mM K+预收缩后诱导剂量依赖性收缩。相比之下，在静脉中用血栓素A2（TXA2）类似物U46619或前列腺素F2α（PGF2α）预收缩后，BPS诱导剂量依赖性舒张。在动脉中，用NE预收缩后，BPS在较高浓度下诱导收缩。然而，用PGF2α预收缩后，BPS使动脉剂量依赖性舒张。通过用TXA2/内过氧化物受体拮抗剂13-氮杂前列腺酸（13-APA）预处理，BPS在静脉中的剂量反应曲线向右移动。Schild图分析得出线性回归，斜率为0.86±0.13，与1无显著差异，13-APA对BPS的pA2值为7.10±0.06。通过用BPS预处理，U46619在静脉中的剂量反应曲线向右移动。Kaumann图分析得出线性回归，斜率为0.89±0.09，与1无显著差异，BPS对U46619的pA2值为5.68±0.04。这些发现表明BPS是TXA2/内过氧化物受体的部分激动剂。
