Molsidomine on cardiovascular leukotriene D₄ actions

Summary

Anaesthetized open-chest dogs were used to study the effects of intracoronary leukotriene D₄ (LTD₄; 0.5 μg/kg) on haemodynamics, the electrocardiogram (ECG), coronary blood flow in the left circumflex artery and coronary resistance in the absence or presence of the antianginal drug molsidomine (500 μg/kg i.v.). LTD₄ increased left ventricular (LV) filling pressure from 6.5±3.8 to 14.7±3.2 mm Hg (P<0.01), decreased LV dP/dt _max from 2,500±200 to 1,240±205 mm Hg/s (P<0.05), elevated the S-T segment of the ECG from 0.3±0.2 to 2.4±0.6 mV (P<0.01), and coronary resistance from 3.4±0.9 to 33.7±4.8 mm Hg×min×ml⁻¹ (P<0.001). Coronary artery blood flow fell from 33.8±2.7 to 3±3 ml/min (P<0.001). Molsidomine treatment 15 min prior to repeated intracoronary LTD₄ application attenuated vasoconstrictor response to LTD₄ and the subsequent elevation in total coronary vascular resistance. The negative inotropic actions of the eicosanoid were counteracted by molsidomine. Filling pressure decreased and no temporary signs of ischaemia were noted in the ECG. Inhibition of the cyclooxygenase enzyme activity by i.v. indomethacin (5 mg/kg) had no effects on the LTD₄-induced haemodynamic alterations, the ECG, and coronary flow and resistance. The antagonistic molsidomine actions on haemodynamic and electrocardiographic LTD₄ effects were not influenced by previous indomethacin treatment. Thus, molsidomine actions on haemodynamics and assumed influences of the drug or its main metabolite on platelet function and platelet and coronary vascular eicosanoid formation may protect the heart against LTD₄-caused derangements.