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We investigated the effects of leukotriene (LT) D 4 and its novel potent and selective antagonist L-660,711 on isolated rat hearts with chronic myocardial infarction. The left coronary artery was ligated permanently or for 30 or 60 min and followed by reperfusion. Hearts were isolated and perfused in the Langendorff mode 4 days, 4 wk, or 8 wk after the operation. Dose-response curves for LTD 4 (12-240 ng/min) on coronary flow were shifted to the left in rats with permanent coronary occlusion for 8 wk or with coronary occlusion for 30 or 60 min and reperfusion for 4 wk. In contrast, dose-response curves were unchanged in rats 4 days after myocardial infarction. L-660,711 shifted dose-response curves for LTD 4 on coronary flow to the right in all groups. The negative inotropic and chronotropic effects of LTD 4 could be markedly attenuated by L-660,711 in all groups. Our findings suggest that the effect of LTD 4 is enhanced in rat hearts with chronic myocardial infarction. L-660,711 effectively antagonized the vasoconstrictor effect of exogenous LTD 4 .

Type

Journal article

Journal

American Journal of Physiology - Heart and Circulatory Physiology

Publication Date

01/01/1994

Volume

266