Waring P H, Hyman A L, Nandiwada P A, Kadowitz P J
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Prostaglandins Leukot Essent Fatty Acids. 1988 Mar;31(3):117-22. doi: 10.1016/0952-3278(88)90107-x.
The effects of OKY-1581, a thromboxane synthesis inhibitor, on pulmonary vascular responses to arachidonic acid (AA) were investigated under baseline and elevated tone conditions in the intact chest cat. Under conditions of controlled blood flow at baseline tone, intralobar injections of AA increased lobar arterial pressure in a dose-related manner. These pressor responses were reduced by OKY-1581, and a small vasodilator response was unmasked. The administration of indomethacin to these same animals abolished all responses to AA. When baseline tone in the pulmonary vascular bed was elevated by infusion of U46619, intralobar injections of AA caused a biphasic change in lobar arterial pressure characterized by an initial increase followed by a secondary fall in pressure. Treatment with OKY-1581 attenuated the pressor component of the response and enhanced the depressor component of the response. All responses to AA at elevated tone were also blocked by indomethacin. Pressor responses to intralobar injections of U46619 were not altered by OKY-1581 or indomethacin and were similar under baseline and high pulmonary vascular tone conditions. The results of this study suggest that the pulmonary pressor response to AA in the cat is dependent in large part on the formation of TXA2 and also suggest that TXA2, PGI2, and vasoconstrictor prostaglandins (PGF2 alpha, PGD2, PGE2) are formed from AA in the cat lung.
在开胸猫的基线和高张力条件下，研究了血栓素合成抑制剂OKY - 1581对肺血管对花生四烯酸（AA）反应的影响。在基线张力下控制血流的条件下，叶内注射AA可使叶动脉压呈剂量依赖性升高。这些升压反应被OKY - 1581减弱，并揭示出小的血管舒张反应。给这些相同的动物注射吲哚美辛可消除对AA的所有反应。当通过输注U46619使肺血管床的基线张力升高时，叶内注射AA导致叶动脉压出现双相变化，其特征是最初压力升高，随后压力下降。用OKY - 1581治疗可减弱反应的升压成分并增强反应的降压成分。在高张力下对AA的所有反应也被吲哚美辛阻断。对叶内注射U46619的升压反应不受OKY - 1581或吲哚美辛的影响，并且在基线和高肺血管张力条件下相似。本研究结果表明，猫对AA的肺升压反应在很大程度上依赖于血栓素A2（TXA2）的形成，并且还表明TXA2、前列环素（PGI2）和血管收缩性前列腺素（前列腺素F2α、前列腺素D2、前列腺素E2）是由猫肺中的AA形成的。
