ENHANCED ADRENERGIC NEUROTRANSMISSION IN DIABETIC RABBIT CAROTID-ARTERY

Objective: The aim was to examine the effects of diabetes mellitus on adrenergic neurotransmission and smooth muscle responsiveness in the d ensely innervated carotid artery from six-week alloxan diabetic rabbit s. Methods: Rings of carotid arteries were isolated from normal and di abetic rabbits and isometric tension was measured in response to stimu lation of adrenergic nerves, alpha adrenoceptors, and activation by ca lcium. Results: Basal content and stimulated overflow of endogenous no radrenaline were reduced by approximately 25% in arteries from diabeti c as compared to normal rabbits, In contrast, responses to endogenous noradrenaline released from adrenergic nerves by electrical stimulatio n or tyramine displacement were not different between arteries from no rmal and diabetic groups. Neuronal uptake blockade using cocaine cause d a significantly smaller leftward shift in the contractions produced by electrical stimulation and exogenously applied noradrenaline in art eries from diabetic rabbits. The tonic, but not phasic, contractions c aused by phenylephrine were larger in arteries from diabetic rabbits. Calcium-induced contractions caused by readdition of calcium to a calc ium-free medium containing potassium (15 mmol . litre(-1)) were also s ignificantly larger in arteries from diabetic rabbits. BAY K 8644, a c alcium channel activator, caused an increase in calcium induced contra ctions and abolished the difference between the two groups, Conclusion s: Although neurogenic contractions of diabetic carotid artery are nor mal, there is inefficient or reduced neuronal uptake as well as increa sed activity of calcium channels in the smooth muscle which increase c ontractions to cr adrenoceptor agonists.