Potentiation by endothelin‐1 of 5‐hydroxytryptamine responses in aortae from streptozotocin‐diabetic rats: a role for thromboxane A2

Gail M. James, Wayne C. Hodgson

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Abstract

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 the present study, the thromboxane A2/prostaglandin H2 (TP) receptor antagonist GR32191B (1 μm) significantly reduced maximum responses to 5‐HT in endothelium‐intact aortae from both control and diabetic rats. In the presence of GR32191B, maximum responses to 5‐HT, in endothelium‐intact aortae from diabetic rats, were still significantly reduced compared to those obtained in aortae from controls. 3 GR32191B (1 μm) had no significant effect on maximum responses to 5‐HT in endothelium‐denuded aortae from either control or diabetic rats. 4 Interaction between 5‐HT (0.1 μm‐0.1 mm) and threshold concentrations of endothelin‐1 (ET‐1) or the thromboxane (Tx)A2‐mimetic, U46619, were examined in endothelium‐intact and ‐denuded aortae from control and 2‐week streptozotocin‐diabetic rats. 5 Maximum responses to 5‐HT in the presence of a threshold concentration of ET‐1 (3 nm), in endothelium‐intact aortae from diabetic rats, were not significantly different from those of control rats. 6 Maximum responses to 5‐HT in the combined presence of ET‐1 (3 nm) and GR32191B (1 μm), 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 of ET‐1 (3 nm) in endothelium‐denuded aortae from diabetic rats were significantly reduced compared to those from controls. 8 Maximum responses 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 significantly different from responses of controls. 9 Maximum responses to 5‐HT in the presence of a threshold (5–20 nm) concentration of U46619, in endothelium‐denuded aortae from diabetic rats, were not significantly different from responses of controls. 10 The results of the present study indicate that endothelial‐derived TxA2 contributes to the contractile response to 5‐HT in aortae from control and diabetic rats. Endothelial‐derived TxA2 also appears to play a role in the potentiation of 5‐HT responses by ET‐1 in aortae from diabetic rats. 1995 British Pharmacological Society

Original languageEnglish
Pages (from-to)1236-1240
Number of pages5
JournalBritish Journal of Pharmacology
Volume114
Issue number6
DOIs
Publication statusPublished - Mar 1995

Keywords

  • 5‐hydroxytryptamine
  • diabetes
  • Endothelin‐1
  • rat aortae
  • thromboxane A

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