REVERSAL BY L-ARGININE OF A DYSFUNCTIONAL ARGININE NITRIC-OXIDE PATHWAY IN THE ENDOTHELIUM OF THE GENETIC DIABETIC BB RAT

We examined the effects of acute supplementation with arginine in vitr o on endothelium-dependent relaxation in aortic rings taken from femal e genetic, diabetes-prone BE rats. Sensitivity to norepinephrine-induc ed contraction was unaltered in rings of diabetic BE rats compared to rings from non-diabetic littermates. In precontracted rings, acetylcho line produced a concentration-dependent relaxation which was impaired by diabetes. This relaxation was blocked by L-nitroarginine in both co ntrol and diabetic rings. Addition of 3 mmol/l L-arginine (but not D-a rginine) enhanced relaxation in diabetic rings similar to that seen in control rings without arginine. L-arginine had no effect on acetylcho line-induced relaxation in control rings. In contrast, relaxation-indu ced by nitroglycerin in diabetic rings without endothelium was not alt ered by L-arginine treatment. Thus, a defect in the utilization of arg inine by nitric oxide synthase exists in the endothelium of the diabet ic BE rat.