Effect of a new phosphodiesterase type III inhibitor as a coronary vasodilator and positive inotropic agent.

Abstract

Isolated rabbit coronary arteries, aortic strips, and a working rabbit heart preparation were used to assess the positive inotropic and vasodilator effects of a newly developed positive inotropic compound, CI 914. The substance had a relaxing effect on histamine preconstricted coronary arteries and aortic strips. At concentrations of 10(-4) mol.litre-1 the relaxing effect on the coronary arteries was significant only at a histamine concentration of 3 x 10(-4) mol.litre-1 (p less than 0.01) whereas at a concentration of 10(-3) mol.litre-1 the relaxing effect was significant at histamine concentrations of from 3 x 10(-5) mol.litre-1 to 3 x 10(-4) mol.litre-1. Aortic strips were more sensitive to the relaxing effect of CI 914, which was significant with 10(-4) mol.litre-1 at histamine concentrations of 3 x 10(-6) to 3 x 10(-4) (p less than 0.05 to p less than 0.01). In the isolated working heart preparation topically sprayed histamine significantly increased total and large coronary artery resistances (p less than 0.001 and p less than .01). This effect was significantly reduced (p less than 0.01 and p less than 0.02) when CI 914 10(-4) mol.litre-1 was present in the perfusion fluid. These findings show that the phosphodiesterase inhibitor CI 914, a positive inotropic agent, induces vasodilation in isolated coronary arteries and aortic strips of the rabbit and reduces the constriction of coronary arteries induced by histamine in the isolated working rabbit heart preparation.