Evaluation of the mechanism of endothelial dysfunction in the genetically-diabetic BB rat.
Endothelial dysfunction is known to occur in chemically-induced animal models of diabetes. The BB diabetic rat is a genetic diabetes-prone model which more closely resembles Type I diabetes mellitus. In this study, we examined the role of superoxide anion radical and cyclooxygenase activity on endothelial dysfunction in aorta of the spontaneous diabetic BB rat. Vascular endothelial function was studied in vitro in aortic rings from 8-wk diabetic rats and age-matched nondiabetic littermates. There was no alteration in reactivity to norepinephrine as a result of diabetes. Relaxation to acetylcholine (but not nitroglycerin) was impaired in diabetic rings. Relaxation to acetylcholine was abolished by 100 microM L-nitroarginine but unaltered by an equimolar concentration of aminoguanidine (an inducible nitric oxide synthase inhibitor) in both control and diabetic rings. Incubation with 10 microM indomethacin did not alter relaxation to acetylcholine in either control or diabetic rings. In contrast, addition of 20 U/ml superoxide dismutase enhanced relaxation to acetylcholine in diabetic rings but had no effect on relaxation to acetylcholine in control rings. Thus, nitric oxide-mediated, endothelium-dependent relaxation is diminished in aortic rings of the genetic diabetic BB rat. Furthermore, superoxide anion radicals but not cyclooxygenase products play an important role in endothelial dysfunction in this genetic diabetic model.
Pieper
G M
GM
Department of Transplant Surgery, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, Milwaukee, 53226 USA.
Moore-Hilton
G
G
Roza
A M
AM
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D051381:Rats; D011913:Rats, Inbred BB; D012016:Reference Values; D014664:Vasodilation / Q000187:drug effects
D004791:Enzyme Inhibitors; D006146:Guanidines; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; C004479:pimagedine; D007213:Indomethacin