Attenuated 5-HT2 receptor-mediated responses in hindquarters of diabetic rats

Vasoconstrictor responses to 5-hydroxytryptamine (5-HT), alpha-methyl-5-HT, endothelin-1, arachidonic acid and the thromboxane A2-mimetic U46619 ((15S)-hydroxy-11 alpha, 9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid) were obtained in blood-perfused hindquarters of 6-week streptozotocin-diabetic rats. When compared to responses obtained in hindquarters of control rats, responses to 5-HT, alpha-methyl-5-HT, and arachidonic acid were attenuated in hindquarters of diabetic rats. However, responses to endothelin-1 or U46619 were not significantly different between controls and diabetics. These results suggest that 5-HT2, but not endothelin ETA receptor-mediated responses are reduced in hindquarters 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.