EFFECT OF THE NEW NITRATE ESTER ITF-296 ON CORONARY AND SYSTEMIC HEMODYNAMICS IN THE CONSCIOUS DOG - COMPARISON WITH NITROGLYCERIN AND NICORANDIL

The coronary and systemic hemodynamic effects of the novel nitrate est er ITF 296 were investigated in conscious, resting dogs and compared w ith nitroglycerin and nicorandil. ITF 296 at 1-25 mu g/kg i.v. elicite d selective, long-lasting, and dose-dependent increases in large epica rdial coronary artery diameter (CD) without affecting coronary blood f low (CBF) or coronary vascular resistance (CVR). Blood pressure (BP) a nd heart rate (HR) were also unaltered. At 125 mu g/kg, ITF 296 furthe r increased CD but simultaneously reduced CVR and mean aortic pressure and increased CBF and HR. Nitroglycerin 1-25 mu g/kg induced a shorte r and less selective dilatation of large coronary conductance arteries , as it was accompanied by a decrease in CVR at all doses used. Nicora ndil produced a selective increase in left circumflex CD only at the l owest dose used (10 mu g/kg), whereas higher doses were effective on b oth CD and CVR. ITF 296 significantly reduced left ventricular end-dia stolic pressure and increased stroke volume (SV) and cardiac output (C O) at doses that did not alter HR or BP, indicating an increase in car diac efficiency. In contrast, the increases in CO produced by nitrogly cerin and nicorandil were dependent on the augmentation of HR, because SV was unchanged at all doses used. Nitroglycerin dose-dependently de creased BP, whereas ITF 296 reduced BP only at the highest dose used. In conclusion, ITF 296 induces a selective, flow-independent dilatatio n of large coronary conductance arteries without affecting the tone of small coronary resistance vessels or systemic hemodynamics over a bro ad range of doses. An equally selective effect was elicited by nicoran dil only at the lower dose used, whereas no selective effect of nitrog lycerin on the diameter of coronary conductance arteries was seen at t he doses utilized in this study.