Unique coronary vasodilator induction by leukotriene D₄

Coronary blood flow (CBF) and myocardial contractility decrease markedly in response to intracoronary administration of leukotriene D₄ (LTD₄). With steady infusion, however, both CBF and contractility escape, approaching preinfusion values despite ongoing LTD₄ administration. To clarify the mechanism of this escape, we reinfused plasma from the coronary vein draining the myocardial area receiving LTD₄. Introducing this plasma into a coronary artery caused a marked rise in coronary flow for the duration of the plasma infusion. Coronary flow reduction with vasopressin or mechanical occlusion matching that caused by LTD₄ failed to elicit vasodilator production. Thus a unique coronary vasodilator factor is induced by LTD₄. Whole blood or platelet-rich plasma incubated with LTD₄ in vitro produced the same pattern of coronary dilation on intracoronary infusion; LTD₄ incubation with platelet-poor plasma failed to elicit a vasodilation. The vasodilator factor is stable and is not potassium, a prostaglandin, catecholamine, histamine, serotonin, adenosine, adenosine diphosphate, or platelet-activating factor. Production of this leukotriene-induced vasodilator factor may account for the escape from LTD₄-induced coronary constriction.