Characteristic cardiovascular effects of RA642, a pyrimido-pyrimidine derivative, in anesthetized dogs

The hemodynamic effects of RA642, a pyrimido-pyrimidine derivative, were studied in dogs anesthetized with pentobarbital. The i.v. injection of RA642 (0.25 mg/kg) produced significant increases in systemic blood pressure (from 126 +/- 5 to 152 +/- 7 mm Hg 10 min after injection), cardiac output (from 1.37 +/- 0.11 to 2.07 +/- 0.11 liters/min) and left ventricular dP/dt (from 4658 +/- 557 to 6628 +/- 912 mm Hg/sec). Blood flow in coronary, renal and superior mesenteric arteries increased significantly after the injection (from 62 +/- 5 to 79 +/- 6 ml/min, from 142 +/- 5 to 174 +/- 5 ml/min and from 205 +/- 16 to 248 +/- 10 ml/min 10 min after the injection, respectively). Total peripheral and pulmonary vascular resistance were reduced significantly (from 7320 +/- 510 to 5980 +/- 512 dyn X sec/cm5 and from 250 +/- 10 to 220 +/- 12 dyn X sec/cm5, respectively, 10 min after injection). There were no significant changes in heart rate, pulmonary arterial pressure, pulmonary capillary wedge pressure or central venous pressure. With either pretreatment using hexamethonium or with the administration of phenoxybenzamine and propranolol together, hemodynamic effects caused by RA642 did not occur. With pretreatment using atropine, RA642 caused a significant increase in the heart rate. Perfusion pressure in an isolated hind-limb was reduced by the direct administration of RA642 into the perfusion circuit in a dose-dependent way. The vasodilating effect of this compound was prevented by pretreatment with papaverine but not with propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)