Adrenergic denervation in rabbits with diabetes mellitus.

The influence of alloxan-induced diabetes mellitus on the sympathetic neuroeffector junction of the rabbit carotid artery denuded of endothelium was studied. Six weeks of diabetes resulted in a neuropathy characterized by a 38% reduction in the arterial content of norepinephrine. Norepinephrine release from the nerves measured from electrically stimulated superfused arterial segments was decreased. The cocaine-sensitive accumulation of [3H]-norepinephrine (NE) was also reduced, reflecting decreased neuronal uptake. The consequences of these prejunctional changes were studied by measuring isometric contractions of arterial rings caused by electrical nerve stimulation or by exogenous norepinephrine. Despite the reduced release of norepinephrine, neurogenic contractions were normal, suggesting an increased sensitivity of the smooth muscle. After neuronal uptake was blocked, the neurogenic contractions of diabetic arteries were less than normal, reflecting the reduction in transmitter release. The sensitivity of diabetic arteries to exogenous norepinephrine was increased under control conditions; maximal contractions were unchanged. Blockade of norepinephrine uptake increased norepinephrine sensitivity more in normal than in diabetic arteries, and there was no longer a significant difference in sensitivity. Thus, under control conditions, neurogenic contractions of the partially denervated diabetic rabbit carotid artery are paradoxically normalized by increased alpha-adrenergic sensitivity of the smooth muscle. The increased sensitivity caused by reduced neuronal uptake can thus preserve neurogenic vasoconstriction and cause supersensitivity to exogenous catecholamines in the sympathetic neuropathy caused by diabetes mellitus.