Augmentation of leukotriene C4 and D4 release due to severe stenosis in the canine coronary artery stimulated by the calcium ionophore A23187.
In dogs undergoing 24- or 72-hr severe narrowing of the left anterior descending coronary artery (LAD), the in vitro formation of immunoreactive leukotriene C4 (LTC4) by the stenosed LAD was greatly augmented by 1 microM A23187 in a 10-min incubation at 37 degrees. This stimulated LTC4 formation was abolished by 30 microM nordihydroguaiaretic acid (NDGA). The incubation products were identified by high performance liquid chromatography and radioimmunoassay to be largely composed of LTC4 and LTD4 in similar proportion. In contrast to the stenosed LAD, the non-stenotic left circumflex coronary artery, apex of the heart, and renal artery of the same experimental animals failed to respond to the calcium ionophore up to 10 microM. The vascular and cardiac tissues from sham-operated animals also remained quiescent in the presence of A23187. The normal coronary artery showed low levels of leukotriene formation and was resistant to the ionophore. It is proposed that a latent portion of leukotriene synthesis, which can be triggered by the calcium ionophore, may play a significant role in the pathogenesis of coronary artery spasm associated with acute myocardial infarction and angina pectoris in patients with obstructive coronary artery disease.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003327:Coronary Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D013189:SRS-A / Q000378:metabolism*; D013997:Time Factors
D013189:SRS-A; D000001:Calcimycin; D009637:Masoprocol