Ezeamuzie I C, Assem E S
Agents Actions. 1983 Apr;13(2-3):182-7. doi: 10.1007/BF01967327.
Synthetic leukotrienes C4 and D4 (LTC and LTD) were found to possess potent coronary vasoconstrictor and cardiac depressant actions on isolated guinea-pig hearts. We therefore went further to investigate the possibility that endogenously released slow-reacting substance of anaphylaxis (SRS-A) might be responsible for the coronary vasoconstriction and negative inotropism in guinea-pig cardiac anaphylaxis. Results using time-course analysis as well as the specific SRS antagonist FPL 55712 have shown that SRS-A released during cardiac anaphylaxis was unlikely to be responsible for the early and most dramatic phase of coronary vasoconstriction that usually occurred at the 2nd min after antigen challenge, but could possibly be responsible for the latter and more prolonged phase occurring between the 6th and 14th min. This is because SRS-A release was found to peak at the 4th min after antigen challenge, 2 min after vasoconstriction had already peaked. Moreover, this early component of coronary vasoconstriction could not be blocked by FPL 55712, whereas the latter component was significantly reduced by the antagonist. The negative inotropism following cardiac anaphylaxis was also found to be significantly reduced by FPL 55712, thus suggesting SRS-A involvement. However, our experiments did not show whether the two actions were direct effects of SRS-A or whether contractility failure was a consequence of coronary vasoconstriction.
已发现合成白三烯C4和D4（LTC和LTD）对离体豚鼠心脏具有强大的冠状动脉血管收缩和心脏抑制作用。因此，我们进一步研究内源性释放的过敏反应慢反应物质（SRS-A）是否可能是豚鼠心脏过敏反应中冠状动脉血管收缩和负性肌力作用的原因。使用时程分析以及特异性SRS拮抗剂FPL 55712的结果表明，心脏过敏反应期间释放的SRS-A不太可能是通常在抗原攻击后第2分钟出现的冠状动脉血管收缩早期和最显著阶段的原因，但可能是在第6至14分钟之间出现的后期和更持久阶段的原因。这是因为发现SRS-A释放在抗原攻击后第4分钟达到峰值，此时血管收缩已经达到峰值2分钟之后。此外，冠状动脉血管收缩的早期成分不能被FPL 55712阻断，而后期成分被拮抗剂显著降低。心脏过敏反应后的负性肌力作用也被FPL 55712显著降低，因此提示SRS-A参与其中。然而，我们的实验并未表明这两种作用是SRS-A的直接作用，还是收缩力衰竭是冠状动脉血管收缩的结果。
