CARDIOVASCULAR EFFECTS OF ISOSORBIDE DINITRATE INFUSED INTRAVENOUSLY INTO ANAESTHETIZED DOGS

Abstract

The cardiohaemodynamic response and the development of tolerance to isosorbide dinitrate (ISDN) were examined in anaesthetized, open-chest dogs. ISDN, infused intravenously (i.v.) for 2 h at a rate of 10 or 30 micrograms/kg per min, decreased systemic blood pressure (systolic, mean and diastolic; SBP), left ventricular (LV) systolic and end-diastolic pressure, LVdP/dt max, pressure-rate product and coronary blood flow. No significant changes in heart rate (HR) and coronary vascular resistance were observed. Intravenous ISDN significantly attenuated the vasodilator effect of bolus intracoronary (i.a.) glyceryl trinitrate (GTN, 1 micrograms), and ISDN (30 micrograms), whereas that of bolus i.a. nicorandil (mononitrate, 20 micrograms) remained unaffected. Just after acute tolerance towards i.a. ISDN was provoked 1 h after starting ISDN infusion (30 micrograms/kg per min, i.v.), the combined infusion of ISDN (i.v.) and nicorandil (30 micrograms/kg per min) was instigated for a further hour. Also, 1 h after the onset of vehicle infusion (i.v.), the combined infusion of vehicle and nicorandil (30 micrograms/kg per min, i.v.) was started. There were essentially no significant differences between the corresponding values concerning the coronary vascular responses obtained from the two combined infusion groups.