EFFECT OF ENDOTHELIUM ON DIABETES-INDUCED CHANGES IN CONSTRICTOR RESPONSES MEDIATED BY 5-HYDROXYTRYPTAMINE IN RAT AORTA

We investigated constrictor responses to 5-hydroxytryptamine (5-HT) an d 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, a 5-HT2/5-HT1c r eceptor agonist) of aortic rings from 2- and 6-week streptozotocin-dia betic and vehicle control rats. At 10 g resting tension, maximum respo nses and -log EC50 Values to 5-HT were significantly reduced in endoth elium-intact and denuded aortas from 2- and 6-week diabetic rats relat ive to those from control rats (except for -log EC50 Of endothelium-in tact rings from 6-week diabetic rats). Removal of endothelium from aor tas of 2- and 6-week diabetic and control rats caused significant incr eases both in -log EC50 values and in maximum responses to 5-HT. DOI c aused marked contraction of endothelium-denuded aortas from control ra ts, but not of endothelium-intact aortas from control rats or aortas ( either with or without endothelium) from diabetic rats. The nitric oxi de (NO) synthase inhibitor N-nitro-L-arginine (NOLA) significantly pot entiated constrictor responses to 5-HT in endothelium-intact aortas fr om control and diabetic rats. NOLA significantly potentiated constrict or responses to DOI in endothelium-intact aortas from control rats, bu t not in endothelium-intact aortas from diabetic rats. These results s uggest that for aortas from 2- and 6-week diabetic rats, the diminishe d responses to 5-HT and DOI may be a result of reductions in 5-HT2-rec eptor-mediated responses of smooth muscle. The results also suggest th at 5-HT and DOI can stimulate NO release from endothelial cells.