PHOSPHODIESTERASE INHIBITORS PREVENT ENDOTHELIN-INDUCED VASOCONSTRICTION, BRONCHOCONSTRICTION, AND THROMBOXANE RELEASE IN PERFUSED RAT LUNG

Endothelin-1 (ET-1) causes broncho- and vasoconstriction in the rat is olated perfused lung and induces the release of thromboxane and prosta cyclin, Pharmacological inhibition of phosphodiesterases (PDE) is know n to relax airway and vascular smooth muscle and it attenuates the rel ease of pro-inflammatory mediators. Therefore, we examined whether and how rolipram (specific for PDE IV) and motapizone (specific for PDE I II) affect ET-1-elicited changes in lung function. 5 mu M motapizone a ttenuated broncho- and vasoconstriction to a greater extent than 5 mu M rolipram, Simultaneous pretreatment with both PDE inhibitors protect ed completely, Thromboxane release was suppressed by rolipram, but not by motapizone. Prostacyclin release was neither influenced by single, nor by combined pretreatment with either compound, We conclude that c ombined inhibition of PDE III and IV counteracts ET-1-elicited pressor - and inflammatory actions in the lung. (C) 1997 Academic Press.