POTENTIATION BY ENDOTHELIN-1 OF 5-HYDROXYTRYPTAMINE RESPONSES IN AORTAE FROM STREPTOZOTOCIN-DIABETIC RATS - A ROLE FOR THROMBOXANE A(2)

1 We have previously reported maximum responses to 5-hydroxytryptamine (5-HT) are diminished in endothelium-intact and -denuded aortae from rats with streptozotocin-induced diabetes of 2-weeks duration. 2 In th e present study, the thromboxane A(2)/prostaglandin H-2 (TP) receptor antagonist GR32191B (1 mu M) significantly reduced maximum responses t o 5-HT in endothelium-intact aortae from both control and diabetic rat s. In the presence of GR32191B, maximum responses to 5-HT, in endothel ium-intact aortae from diabetic rats, were still significantly reduced compared to those obtained in aortae from controls. 3 GR32191B (1 mu M) had no significant effect on maximum responses to 5-HT in endotheli umdenuded aortae from either control or diabetic rats. 4 Interaction b etween 5-HT (0.1 mu M-0.1 mM) and threshold concentrations of endothel in-1 (ET-1) or the thromboxane (Tx)A(2)-mimetic, U46619, were examined in endothelium-intact and -denuded aortae from control and 2-week str eptozotocin-diabetic rats. 5 Maximum responses to 5-HT in the presence of a threshold concentration of ET-1 (3 nM), in endothelium-intact ao rtae from diabetic rats, were not significantly different from those o f control rats. 6 Maximum responses to 5-HT in the combined presence o f ET-1 (3 nM) and GR32191B (1 mu M), in endothelium-intact aortae from diabetic rats, were significantly reduced compared to those obtained in aortae from controls. 7 Maximum responses to 5-HT in the presence o f ET-1 (3 nM) in endothelium-denuded aortae from diabetic rats were si gnificantly reduced compared to those from controls. 8 Maximum respons es to 5-HT in the presence of a threshold concentration of U46619 (20 or 30 nM), in endothelium-intact aortae from diabetic rats, were not s ignificantly different from responses of controls. 9 Maximum responses to 5-HT in the presence of a threshold (5-20 nM) concentration of U46 619, in endothelium-denuded aortae from diabetic rats, were not signif icantly different from responses of controls. 10 The results of the pr esent study indicate that endothelial-derived TxA(2) contributes to th e contractile response to 5-HT in aortae from control and diabetic rat s. Endothelial-derived TxA(2) also appears to play a role in the poten tiation of 5-HT responses by ET-1 in aortae from diabetic rats.