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.