In vivo and in vitro evidence of altered nitric oxide metabolism in the spontaneously diabetic, insulin‐dependent BB/Edinburgh rat

Altered vasoreactivity may contribute significantly to the pathogenesis of diabetic vascular complications. This study investigated the effect of (a) insulin‐treated diabetes, and (b) chronic in vivo administration of Nω‐nitro‐l‐arginine methyl ester (l‐NAME), a nitric oxide (NO) synthase inhibitor, on mean arterial pressure and in vitro vascular reactivity to noradrenaline in mesenteric arterial bed preparations from spontaneously diabetic, insulin‐dependent and treated BB rats, the best animal model of insulin‐dependent mellitus (IDDM) currently available. Four groups of animals from the Edinburgh colony (BB/E) of spontaneously diabetic BB rats were studied: age‐matched (mean±s.e.mean=156±2d) non‐diabetic (glycated haemoglobin=3.8±0.1%) and insulin‐treated diabetic (glycated haemoglobin=6.2±0.5%; duration of diabetes=56±4 d) groups were either l‐NAME treated (oral dose=27±1 mg kg−1 d−1; duration of treatment from 30 until 153 days of age) or untreated. Although our diabetic BB/E rats do not achieve overall normoglycaemia, individual adjustment of the daily insulin dose administered to every diabetic rat achieves better glycaemic control than previous groups studying altered vascular reactivity and endothelial dysfunction in this animal model of diabetes. Mean arterial pressure (measured directly via indwelling carotid arterial cannulae) was not significantly different between non‐diabetic (116±3 mmHg; n=10) and diabetic (122±2 mmHg; n=12) BB/E rats. l‐NAME treatment significantly (P