Influences of Cardiovascular Drugs on Leukotriene D4 Action

In anesthetized dogs, the effects of intracoronary leukotriene D4 (LTD4) (0.5 μg/kg) were studied on hemodynamics, the electrocardiogram (ECG) (lead II), flow in the left circumflex (LCX) coronary artery, and resistance in the absence or presence of intravenously administered cardiovascular drugsnifedipine (10 μg/kg), nitroglycerin (5 μg/kg/min), isosorbide dinitrate (100 μg/kg), molsidomine (500 μg/kg), propranolol (500 μg/kg), and phentolamine (250 μg/kg). LTD4 increased left ventricular end-diastolic pressure (LVEDP) by 126% (p < 0.01), the S-T segments of the ECG from 0.3 to 2.4 mV (p < 0.001), and coronary resistance from 3.5 to 35.7 mm Hg x min x ml (p < 0.001). LCX blood flow fell from 33.8 to 3 ml/min (p < 0.001), and LV dP/dtmax decreased by 51% (p < 0.05). Nitroglycerin and isosorbide dinitrate were ineffective on cardiovascular LTD4 actions. Nifedipine and molsidomine inhibited the coronary flow reduction with LVEDP and S-T segment elevation by the LTD4 vasoconstriction. Negative inotropic LTD4 effects were counteracted by molsidomine. Phentolamine augmented the degree and duration of coronary constriction after LTD4. Propranolol weakened the coronary and circulatory eicosanoid actions. Indomethacin (5 mg/kg, i.v.) neither abolished the LTD4-caused hemodynamic and electrocardiographic consequences, nor attenuated beneficial nifedipine or molsidomine antagonism. Thus, it can be considered that nifedipine may inhibit the Ca influx required for the effects of exogenously administered LTD4. LTD4 apparently does not act over cardiac α- or β-receptor activation. Molsidomine effects on cardiohemodynamics with platelet and coronary vascular eicosanoid actions may protect the heart against LTD4induced derangement.