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 nitric oxide is a potent endogenous nitrovasodilator, and endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor substance. They play a major role in the modulation of vascular tone. Selective impairment of endothelium-dependent relaxation and impaired vasoconstriction in response to ET-1 could result in vascular disorders. The purpose of our study was to determine whether vascular responses to ET-1 and endothelium-dependent relaxing substances are impaired in rats with streptozotocin-induced diabetes of 2 weeks duration. Endothelium-dependent relaxations produced by carbachol and ATP in aortic rings precontracted with phenylephrine were significantly attenuated in rings from diabetic rats, but the endothelium-independent relaxations produced by sodium nitroprusside and adenosine in diabetic preparations were not changed when compared to the corresponding controls. The ET-1-induced contractions were significantly attenuated with no change in agonist potency (pD2 value) in aortae with and without endothelium obtained from diabetic rats when compared to those from controls. Mechanical removal of the endothelium did not significantly change ET-1 responses of aortae from either diabetic or control rats compared with responses of aortae with intact endothelium. These results suggest that, in this diabetic model, the contractile responsiveness of thoracic aortic muscles and the endothelial functions are significantly altered during 2 weeks of diabetes.
Utkan
T
T
Department of Pharmacology and Toxicology, Faculty of Medicine, Kocaeli University, Turkey.
Sarioglu
Y
Y
Yildirim
S
S
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D019332:Endothelin-1 / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D019332:Endothelin-1; D018721:Muscarinic Agonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013311:Streptozocin; D000255:Adenosine Triphosphate; D002217:Carbachol; D000241:Adenosine