Effect of Endothelium on Diabetes-Induced Changes in Constrictor Responses Mediated by 5-Hydroxytryptamine in Rat Aorta

Abstract

We investigated constrictor responses to 5-hydroxytryptamine (5-HT) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, a 5-HT2/5-HT1C receptor agonist) of aortic rings from 2- and 6-week streptozotocin-diabetic and vehicle control rats. At 10 g resting tension, maximum responses and -log EC50 values to 5-HT were significantly reduced in endothelium-intact and denuded aortas from 2- and 6-week diabetic rats relative to those from control rats (except for -log EC50 of endothelium-intact rings from 6-week diabetic rats). Removal of endothelium from aortas of 2- and 6-week diabetic and control rats caused significant increases both in -log EC50 values and in maximum responses to 5-HT. DOI caused marked contraction of endothelium-denuded aortas from control rats, but not of endothelium-intact aortas from control rats or aortas (either with or without endothelium) from diabetic rats. The nitric oxide (NO) synthase inhibitor N-nitro-L-arginine (NOLA) significantly potentiated constrictor responses to 5-HT in endothelium-intact aortas from control and diabetic rats. NOLA significantly potentiated constrictor responses to DOI in endothelium-intact aortas from control rats, but not in endothelium-intact aortas from diabetic rats. These results suggest that for aortas from 2- and 6-week diabetic rats, the diminished responses to 5-HT and DOI may be a result of reductions in 5-HT2-receptor-mediated responses of smooth muscle. The results also suggest that 5-HT and DOI can stimulate NO release from endothelial cells.