Effects of calcium entry blockers on coronary constriction and myocardial ischemia due to leukotriene D4.
Recent studies show that leukotrienes (LTs) produce profound coronary artery constriction. Although calcium entry blockers are commonly used to remedy coronary vasospasm, their capacity to interfere with LT-mediated coronary constriction is unknown. Therefore, we compared effects of intracoronary LTD4 before and during treatment with calcium entry blockers in the in situ, blood-perfused hearts of domestic pigs. Intravenous administration of verapamil (0.1-1.6 mg/kg), nifedipine (10 or 100 micrograms/kg) or diltiazem (0.6-2.0 mg/kg) sufficient to increase base-line coronary blood flow (CBF) and decrease mean arterial pressure did not change decrement in CBF after LTD4. Infusion of verapamil (0.01-0.04 mg/min) into the left anterior descending coronary artery raised pre-LTD4 CBF almost 2-fold without alteration in mean arterial pressure, heart rate or left ventricular end-diastolic pressure. Intracoronary boluses of LTD4 (0.3, 1.0 and 3.0 micrograms) during verapamil infusion into the same vessel caused dose-dependent decreases in CBF identical to those observed when LTD4 was injected during control infusion. ECGs showed myocardial ischemia during severe flow reduction after high dose intracoronary LTD4 (3.0 or 10.0 micrograms). When the same LTD4 doses were injected during intracoronary verapamil, electrocardiographic changes did not occur despite similar decreases in CBF. The capacity of verapamil to prevent LTD4-induced ischemia may be caused by higher residual CBF after LTD4 even though the magnitude of LTD4-induced CBF decrement was unaltered. LTD4-induced coronary constriction seems to be mediated by a mechanism unrelated to calcium entry channels blocked by verapamil, nifedipine or diltiazem.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors*; D013552:Swine; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D013189:SRS-A; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium