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 m odel which more closely resembles Type I diabetes mellitus. In this st udy, we examined the role of superoxide anion radical and cyclooxygena se activity on endothelial dysfunction in aorta of the spontaneous dia betic BB rat. Vascular endothelial function was studied in vitro in ao rtic rings from 8-wk diabetic rats and age-matched nondiabetic Litterm ates. There was no alteration in reactivity to norepinephrine as a res ult of diabetes, Relaxation to acetylcholine (but not nitroglycerin) w as impaired in diabetic rings. Relaxation to acetylcholine was abolish ed by 100 mu M L-nitroarginine but unaltered by an equimolar concentra tion of aminoguanidine (an inducible nitric oxide synthase inhibitor) in both control and diabetic rings. Incubation with 10 mu M indomethac in did not alter relaxation to acetylcholine in either control or diab etic rings. In contrast, addition of 20 U/ml superoxide dismutase enha nced relaxation to acetylcholine in diabetic rings but had no effect o n relaxation to acetylcholine in control rings. Thus, nitric oxide-med iated, 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.