In vitro pulmonary vasorelaxant effect of the phosphodiesterase inhibitor enoximone.
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 established. The authors, therefore, have studied its effect on endothelium-dependent relaxation mediated by the endothelium-derived relaxing factor nitric oxide (NO), as well as endothelium-independent relaxation of isolated porcine pulmonary arteries. Enoximone (10(-7) to 10(-4) M) caused a dose-dependent relaxation in all pulmonary arterial rings. This relaxation neither required the presence of the endothelium nor was affected by the addition of the inhibitor of NO synthase omega-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 endothelium. 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.
Butt
A Y
AY
Department of Respiratory Physiology, Papworth Hospital, Cambridge, England.
Dinh-Xuan
A T
AT
Pepke-Zaba
J
J
Cremona
G
G
Clelland
C A
CA
Higenbottam
T W
TW
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D017335:Enoximone / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D017335:Enoximone