ATTENUATED 5-HT2 RECEPTOR-MEDIATED RESPONSES IN HINDQUARTERS OF DIABETIC RATS

Vasoconstrictor responses to 5-hydroxytryptamine (5-HT), alpha-methyl- 5-HT, endothelin-l, arachidonic acid and the thromboxane A(2)-mimetic U46619 ((15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5Z,13E-die noic acid) were obtained in blood-perfused hindquarters of 6-week stre ptozotocin-diabetic rats. When compared to responses obtained in hindq uarters of control rats, responses to 5-HT; alpha-methyl-5-HT, and ara chidonic acid were attenuated in hindquarters of diabetic rats. Howeve r, responses to endothelin-l or U46619 were not significantly differen t between controls and diabetics. These results suggest that 5-HT2, bu t not endothelin ET(A) receptor-mediated responses are reduced in hind quarters of diabetic rats. The results utilising arachidonic acid and U46619 suggest that there may also be a defect in the cyclo-oxygenase cascade during diabetes.