Influences of cardiovascular drugs on leukotriene D4 action.
In anesthetized dogs, the effects of intracoronary leukotriene D4 (LTD4) (0.5 micrograms/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 drugs: nifedipine (10 micrograms/kg), nitroglycerin (5 micrograms/kg/min), isosorbide dinitrate (100 micrograms/kg), molsidomine (500 micrograms/kg), propranolol (500 micrograms/kg), and phentolamine (250 micrograms/kg). LTD4 increased left ventricular end-diastolic pressure (LVEDP) by 126% (p less than 0.01), the S-T segments of the ECG from 0.3 to 2.4 mV (p less than 0.001), and coronary resistance from 3.5 to 35.7 mm Hg X min X ml-1 (p less than 0.001). LCX blood flow fell from 33.8 to 3 ml/min (p less than 0.001), and LV dP/dtmax decreased by 51% (p less than 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 Ca2+ influx required for the effects of exogenously administered LTD4. LTD4 apparently does not act over cardiac alpha- or beta-receptor activation. Molsidomine effects on cardiohemodynamics with platelet and coronary vascular eicosanoid actions may protect the heart against LTD4 induced derangement.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002317:Cardiovascular Agents; D013189:SRS-A; D014665:Vasodilator Agents; D011433:Propranolol; D007213:Indomethacin; D010646:Phentolamine