Phosphodiesterase inhibitors prevent endothelin-1-induced vasoconstriction, bronchoconstriction, and thromboxane...

Endothelin-1 (ET-1) causes broncho- and vasoconstriction in the rat isolated perfused lung and induces the release of thromboxane and prostacyclin. Pharmacological inhibition of phosphodiesterases (PDE) is known to relax airway and vascular smooth muscle and it attenuates the release of pro-inflammatory mediators. Therefore, we examined whether and how rolipram (specific for PDE IV) and motapizone (specific for PDE III) affect ET-1-elicited changes in lung function. 5 microM motapizone attenuated broncho- and vasoconstriction to a greater extent than 5 microM rolipram. Simultaneous pretreatment with both PDE inhibitors protected 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 combined inhibition of PDE III and IV counteracts ET-1-elicited pressor- and inflammatory actions in the lung.