Effects of leukotrienes B4 and C4 on coronary circulation and myocardial contractility.
Arachidonic acid is metabolized to prostaglandins and thromboxane via the cyclooxygenase pathway and to leukotrienes B4, C4, D4, and E4 via the lipooxygenase pathway. A possible role played by leukotrienes in cardiogenic shock resulting from anaphylaxis prompted us to investigate the action of these compounds on coronary vessels and myocardial contractility. In this study leukotriene B4 (LTB4) and C4 (LTC4) were injected directly into the left circumflex (LCx) coronary artery of nine anesthetized Suffolk sheep. LTB4 had no effect on coronary artery blood flow or myocardial contractility, but 3 X 10(-9) mole induced profound transient circulating neutropenia, reflecting the potent chemotactic and chemokinetic properties of this compound. Injecting as little as 1.6 X 10(-11) mole of LTC4 caused a 14.5 +/- 4.3% (mean +/- SE) reduction of LCx coronary artery flow while 1.6 X 10(-10) mole caused a 26.5 +/- 3.7% decrease of LCx coronary artery flow and an 18.1 +/- 3.2% decrease in systolic shortening of the myocardial region supplied by the LCx coronary artery. Since the decrease in systolic shortening was far greater than that expected on the basis of the reduction in coronary artery flow, we postulate that LTC4 has a direct negative inotropic effect. FPL 55712, a receptor antagonist of leukotrienes C4, D4, and E4, blocked the vasoconstriction induced by LTC4 but only partially blocked the negative inotropic effects of LTC4. LTC4 is a potent vasoconstrictor and negative inotropic agent and may play an important role in anaphylactic shock.
D000818:Animals; D006328:Cardiac Catheterization; D002867:Chromones / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009503:Neutropenia / Q000139:chemically induced; D013189:SRS-A / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012756:Sheep
D002867:Chromones; D013189:SRS-A; D007975:Leukotriene B4; C006312:FPL 55712