Endothelin-1 releases prostacyclin and inhibits ex vivo platelet aggregation in the anesthetized rabbit

The effects of porcine endothelin (endothelin-1, ET-1; 1 nmol/kg i.a.) on ex vivo platelet aggregation and platelet cAMP/cGMP levels were investigated in the anesthetized rabbit. ET-1 inhibited ADP-induced platelet aggregation by 83 +/- 9% within 5 min (p less than 0.01). This ET-1-induced inhibition of platelet aggregation lasted for 30 min and was associated with a significant (five- to sixfold) increase in platelet cAMP. However, platelet cGMP levels were unaffected. Indomethacin (5 mg/kg i.v., 20 min prior to ET-1) abolished the ET-1-induced inhibition of ex vivo platelet aggregation as well as the corresponding augmentation of platelet cAMP. Thus, ET-1 inhibits platelet function in vivo due to the release into the circulation of antiplatelet cyclo-oxygenase products, such as prostacyclin (or PGD2).