Effects of PY 108–068, a New Calcium Antagonist, on General Hemodynamics and Regional Blood Flow in Anesthetized Cats

Abstract

The hemodynamic effects of PY 108-068 (PY), a new benzoxadiazolyle dihydropyridine derivative with calcium antagonistic effects on vascular smooth muscle, were investigated in chloralose--urethane-anesthetized open-chest cats. Regional blood flow was measured with tracer microspheres. PY lowered blood pressure and increased cardiac output similarly to nifedipine (N). Unlike the latter drug, PY decreased heart rate without showing evidence of cardiodepression. Right atrial pressure increased slightly less than with N. All these effects were dose dependent in the dose range from 1 to 43 micrograms/kg i.v.. PY and N increased myocardial blood flow to the same extent initially, and redistributed it in favor of the outer layer of the left ventricle. The activity of sublingually administered PY was comparable to that of a similar intravenous dose. An approximately three times larger intraduodenal dose was needed for similar effects. Our results provide preliminary in vivo evidence that it is possible to separate the negative chronotropic from the negative inotropic effects of calcium antagonists.