Molsidomine on cardiovascular leukotriene D4 actions

Anaesthetized open-chest dogs were used to study the effects of intracoronary leukotriene D4 (LTD4; 0.5 micrograms/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 micrograms/kg i.v.). LTD4 increased left ventricular (LV) filling pressure from 6.5 +/- 3.8 to 14.7 +/- 3.2 mm Hg (P less than 0.01), decreased LV dP/dtmax from 2,500 +/- 200 to 1,240 +/- 205 mm Hg/s (P less than 0.05), elevated the S-T segment of the ECG from 0.3 +/- 0.2 to 2.4 +/- 0.6 mV (P less than 0.01), and coronary resistance from 3.4 +/- 0.9 to 33.7 +/- 4.8 mm Hg X min X ml-1 (P less than 0.001). Coronary artery blood flow fell from 33.8 +/- 2.7 to 3 +/- 3 ml/min (P less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)