Mechanisms underlying increased release of endothelin-1 from aorta in diabetic rats

To clarify the mechanism underlying increased endothelin-1 release in diabe tic rats, we examined its release from thoracic aortas obtained from strept ozotocin-induced diabetic rats. The methoxamine-induced contraction was sig nificantly inhibited by BQ-123 plus BQ-788 (specific antagonists for ETA an d ETB receptors) in diabetic, but not control rats. Preincubation with phos phoramidon also inhibited the methoxamine-induced contraction in diabetic b ut not control rats. The expression of prepro endothelin-1 mRNA was signifi cantly enhanced in aortas from streptozotocin-induced diabetic rats. These results suggest that the increases in the basal and cu-agonist-induced rele ase of endothelin-l in the diabetic state may be due to an overexpression o f the mRNA for prepro endothelin-l. (C) 2001 Elsevier Science Inc. All righ ts reserved.