Lee S L, Levitsky S, Feinberg H
Department of Pharmacology, University of Illinois, Chicago.
J Pharmacol Exp Ther. 1991 Jul 1;258(1):292-8.
A vasoconstrictor-induced prostacyclin (PGI2) production in a perfused rat heart was found, suggesting a mitigating role of PGI2 on coronary vasoconstriction. Treatment of the heart with cyclooxygenase inhibitors (aspirin or indomethacin) decreased PGI2 production by more than 90% and paradoxically reduced the vasoconstriction response. The attenuating effect of cyclooxygenase blockade suggested that endogenous prostanoids contribute to serotonin-, vasopressin- or U46619-induced vasoconstriction. Two prostaglandin (PG) H2/thromboxane A2 (TXA2) receptor antagonists, i.e., 13-azaprostanoic acid (13-APA) and SQ 29,548 were used to investigate putative endogenous vasoconstrictor prostanoids on the exogenously induced vasoconstriction. Retrogradely perfused (5-6 ml/min) rat hearts were rendered guiescent, yet responsive to stimuli, by local injection of lidocaine to the atrioventricular node. Changes in coronary vascular resistance (i.e., perfusion pressure at constant flow) were monitored and the cardiac effluent was collected for analysis of 6-keto PGF1 alpha (the stable metabolite of PGI2) as well as PGF2 alpha by radioimmunoassay. Three vasoconstrictors, i.e., serotonin, vasopressin and the TXA2/PGH2 analog U46619, as well as authentic PGD2, PGE2 and PGF2 alpha were infused. PGD2, PGE2 and PGF2 alpha exerted a dose-related coronary vasoconstriction, as did U46619, serotonin and vasopressin. Treatment with 13-APA (100 microM) or SQ 29,548 (100 nM) almost abolished U46619-induced vasoconstriction. The addition of PGH2/TXA2 receptor antagonists also significantly reduced the pressor effect of exogenously administered PGs, serotonin and vasopressin, with the exception that SQ 29,548 did not significantly antagonize PGE2-induced vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
研究发现，灌注大鼠心脏中存在血管收缩剂诱导的前列环素（PGI2）生成，这表明PGI2对冠状动脉收缩具有缓解作用。用环氧化酶抑制剂（阿司匹林或吲哚美辛）处理心脏，可使PGI2生成减少90%以上，且反常地降低了血管收缩反应。环氧化酶阻断的减弱作用表明，内源性前列腺素参与了血清素、血管加压素或U46619诱导的血管收缩。使用两种前列腺素（PG）H2/血栓素A2（TXA2）受体拮抗剂，即13-氮杂前列腺酸（13-APA）和SQ 29548，来研究外源性诱导血管收缩时假定的内源性血管收缩前列腺素。通过向房室结局部注射利多卡因，使逆行灌注（5 - 6毫升/分钟）的大鼠心脏处于静息状态，但对刺激有反应。监测冠状动脉血管阻力（即恒定流量下的灌注压力）的变化，并收集心脏流出液，通过放射免疫分析法分析6-酮基PGF1α（PGI2的稳定代谢产物）以及PGF2α。注入三种血管收缩剂，即血清素、血管加压素和TXA2/PGH2类似物U46619，以及天然的PGD2、PGE2和PGF2α。PGD2、PGE2和PGF2α与U46619、血清素和血管加压素一样，产生剂量相关的冠状动脉收缩。用13-APA（100微摩尔）或SQ 29548（100纳摩尔）处理几乎消除了U46619诱导的血管收缩。添加PGH2/TXA2受体拮抗剂也显著降低了外源性给予的PGs、血清素和血管加压素的升压作用，但SQ 29548对PGE2诱导的血管收缩没有显著拮抗作用。（摘要截取自250字）
