IMPAIRED CONTRACTION AND RELAXATION IN THE AORTA OF STREPTOZOTOCIN-DIABETIC RATS

It is known that diabetes mellitus alters the vascular responsiveness to several vasoconstrictors and vasodilators. Endothelium-derived nitr ic oxide is a potent endogenous nitrovasodilator, and endothelin-1 (ET -1) is a potent endothelium-derived vasoconstrictor substance. They pl ay a major role in the modulation of vascular tone. Selective impairme nt of endothelium-dependent relaxation and impaired vasoconstriction i n response to ET-1 could result in vascular disorders. The purpose of our study was to determine whether vascular responses to ET-1 and endo thelium-dependent relaxing substances are impaired in rats with strept ozotocin-induced diabetes of 2 weeks duration. Endothelium-dependent r elaxations produced by carbachol and ATP in aortic rings precontracted with phenylephrine were significantly attenuated in rings from diabet ic rats, but the endothelium-independent relaxations produced by sodiu m nitroprusside and adenosine in diabetic preparations were not change d when compared to the corresponding controls. The ET-1-induced contra ctions were significantly attenuated with no change in agonist potency (pD(2) value) in aortae with and without endothelium obtained from di abetic rats when compared to those from controls. Mechanical removal o f the endothelium did not significantly change ET-1 responses of aorta e from either diabetic or control rats compared with responses of aort ae with intact endothelium. These results suggest that, in this diabet ic model, the contractile responsiveness of thoracic aortic muscles an d the endothelial functions are significantly altered during 2 weeks o f diabetes.