Abstract
Enoximone is a phosphodiesterase inhibitor that has both positive inotropic and systemic vasorelaxant activities. The latter are mediated by an increase in vascular smooth muscle concentration of cyclic 3'5' guanosine monophosphate. However, the effect of enoximone on pulmonary vasoreactivity is not estab lished. The authors, therefore, have studied its effect on endothelium-depend ent relaxation mediated by the endothelium-derived relaxing factor nitric oxide (NO), as well as endothelium-independent relaxation of isolated porcine pulmo nary arteries.
Enoximone (10-7 to 10-4 M) caused a dose-dependent relaxation in all pulmo nary arterial rings. This relaxation neither required the presence of the endo thelium nor was affected by the addition of the inhibitor of NO synthase ω-nitro-L-arginine methyl ester (10-4 M). Also, the vasorelaxant response of the rings to the endothelium-dependent vasodilator adenosine diphosphate (10-10 to 10-5 M) was not affected by pretreatment with enoximone.
The authors conclude that enoximone is a potent vasodilator that relaxes pulmonary vascular rings through mechanisms independent of the endothe lium. This endothelium-independent vasodilatory effect of enoximone makes it a potentially valuable drug for the treatment of pulmonary hypertension. This particularly applies to diseases in man where NO production by the endothelial cells is impaired.
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