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Recent studies have indicated impaired endotheliumdependent relaxation in arteries of insulin-dependent [1] diabetic (IDDM) patients. The mechanisms for this defect in human blood vessels is not yet understood. Several studies have observed defects in endothelium-dependent relaxation in both conduit and resistance arteries of streptozotocin (STZ)-or alloxaninduced diabetic rats or rabbits (see reviews [2,3]).Another experimental diabetic model which is not as frequently investigated is the spontaneously diabetic BB (Bio-Breeding) rat despite the fact that this model more closely approximates IDDM in man. Currently, only a limited number of studies regarding endothelial function have been conducted in this important model [4][5][6][7]. More importantly, there is no available information regarding specific defects in nitric oxide (NO) production contributing to defective endothelium-dependent relaxation in this model. In this study, we evaluated the efficacy of supplementation with l -arginine (l-ARG) to improve NO synthase-dependent, endothelium-dependent relaxation in the diabetic BB rat. Materials and methodsExperiments were performed in compliance with the National Institutes of Health "Principles of Laboratory Animal Care" (NIH publication No. 85-23, revised 1985). Progeny of the original BB rat colony from the University of Pennsylvania were used in breeding pairs to develop a local colony of diabetic and non-diabetic BB rats. Onset of diabetes was regularly monitored using test strips and glucometer and defined by 2 successive days of elevated glucose concentration less than 11 mmol/l. Diabetic animals received s. c. injections of NPH insulin which was varied to maintain a low level of hyperglycaemia (i. e. approximately 12-14 mmol/l). Female diabetic BB rats and age-matched, diabetic-resistant littermates were Diabetologia (1997) 40: 910-915 Reversal by L-arginine of a dysfunctional arginine/nitric oxide pathway in the endothelium of the genetic diabetic BB rat Summary We examined the effects of acute supplementation with arginine in vitro on endothelium-dependent relaxation in aortic rings taken from female genetic, diabetes-prone BB rats. Sensitivity to norepinephrine-induced contraction was unaltered in rings of diabetic BB rats compared to rings from non-diabetic littermates. In precontracted rings, acetylcholine produced a concentration-dependent relaxation which was impaired by diabetes. This relaxation was blocked by l -arginine had no effect on acetylcholine-induced relaxation in control rings. In contrast, relaxation-induced by nitroglycerin in diabetic rings without endothelium was not altered by l -arginine treatment. Thus, a defect in the utilization of arginine by nitric oxide synthase exists in the endothelium of the diabetic BB rat. [Diabetologia (1997) 40: 910-915]

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