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Unique coronary vasodilator induction by leukotriene D4
Insights
Leukotriene D4 initially constricts coronary blood flow but then induces a unique vasodilator factor. This factor, produced by platelets, explains the escape from constriction during sustained infusion.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Biochemistry
Background:
- Leukotriene D4 (LTD4) causes significant reductions in coronary blood flow (CBF) and myocardial contractility.
- A phenomenon of 'escape' is observed, where CBF and contractility return towards baseline despite continued LTD4 administration.
Purpose of the Study:
- To elucidate the mechanism behind the escape from LTD4-induced coronary vasoconstriction.
- To identify the nature of the factor responsible for the observed vasodilation.
Main Methods:
- Intracoronary infusion of LTD4 and subsequent reinfusion of coronary venous plasma.
- Comparison of LTD4-induced effects with vasopressin or mechanical occlusion.
- In vitro incubation of whole blood, platelet-rich plasma, and platelet-poor plasma with LTD4.
Main Results:
- Plasma from LTD4-infused coronary veins induced coronary vasodilation upon reinfusion.
- LTD4-induced vasodilation was replicated by infusing plasma from LTD4-incubated whole blood or platelet-rich plasma, but not platelet-poor plasma.
- The induced vasodilator factor was stable and distinct from known vasoactive substances.
Conclusions:
- LTD4 induces the production of a unique coronary vasodilator factor.
- Platelets are essential for the production of this LTD4-induced vasodilator factor.
- This factor likely mediates the escape from LTD4-induced coronary vasoconstriction.
Abstract:
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.