Cardiovascular responses to a newly developed phosphodiesterase inhibitor, DN-9693 (7-pyperidinyl-1,2,3,5-tetrahydroimidazo (2,1-b)-quinazolin-2-oneHCl) in dog cross-circulated atrial and ventricular preparations.

Abstract

The cardiovascular effects of DN-9693, a newly synthesized cyclic AMP phosphodiesterase inhibitor, and sulmazole were investigated in an isolated right atrial or left ventricular preparation which was cross-perfused with blood from another support dog. Each substance dose-dependently increased heart rate and decreased blood pressure of the support dog when administered i.v. The hypotensive effects of DN-9693 were about 40 times more potent than those of sulmazole. The positive chronotropic effect of DN-9693 was about 10 times more potent, but the maximal increase in heart rate was much less than that produced by sulmazole. Each substance dose-dependently increased the sinus rate, the right atrial and the left ventricular developed tension in isolated preparations when administered selectively into cannulated arteries. The effects of DN-9693 were about 10-30 times more potent than those of sulmazole, although the maximal positive chronotropic response to DN-9693 was significantly smaller. Positive chrono- and inotropic effects induced by both substances in the isolated, blood-perfused right atrial preparation were not inhibited by treatment with propranolol, but they were consistently attenuated by electrical stimulation of intramural vagal nerve fibers. These results suggest that DN-9693 and sulmazole produce cardiotonic effects by directly increasing the cyclic AMP level in the dog heart. DN-9693 possesses more potent cardiotonic and vasodilating effects than sulmazole, and has a smaller effect on heart rate.