B Tesfamariam1, R A Cohen. 1. Robert Dawson Evans Department of Clinical Research, Boston University Medical Center, MA, USA.
Abstract
OBJECTIVE: The aim was to examine the effects of diabetes mellitus on adrenergic neurotransmission and smooth muscle responsiveness in the densely innervated carotid artery from six-week alloxan diabetic rabbits. METHODS: Rings of carotid arteries were isolated from normal and diabetic rabbits and isometric tension was measured in response to stimulation of adrenergic nerves, alpha adrenoceptors, and activation by calcium. RESULTS: Basal content and stimulated overflow of endogenous noradrenaline were reduced by approximately 25% in arteries from diabetic as compared to normal rabbits. In contrast, responses to endogenous noradrenaline released from adrenergic nerves by electrical stimulation or tyramine displacement were not different between arteries from normal and diabetic groups. Neuronal uptake blockade using cocaine caused a significantly smaller leftward shift in the contractions produced by electrical stimulation and exogenously applied noradrenaline in arteries from diabetic rabbits. The tonic, but not phasic, contractions caused by phenylephrine were larger in arteries from diabetic rabbits. Calcium-induced contractions caused by readdition of calcium to a calcium-free medium containing potassium (15 mmol.litre-1) were also significantly larger in arteries from diabetic rabbits. BAY K 8644, a calcium channel activator, caused an increase in calcium induced contractions and abolished the difference between the two groups. CONCLUSIONS: Although neurogenic contractions of diabetic carotid artery are normal, there is inefficient or reduced neuronal uptake as well as increased activity of calcium channels in the smooth muscle which increase contractions to alpha adrenoceptor agonists.
OBJECTIVE: The aim was to examine the effects of diabetes mellitus on adrenergic neurotransmission and smooth muscle responsiveness in the densely innervated carotid artery from six-week alloxan diabetic rabbits. METHODS: Rings of carotid arteries were isolated from normal and diabetic rabbits and isometric tension was measured in response to stimulation of adrenergic nerves, alpha adrenoceptors, and activation by calcium. RESULTS: Basal content and stimulated overflow of endogenous noradrenaline were reduced by approximately 25% in arteries from diabetic as compared to normal rabbits. In contrast, responses to endogenous noradrenaline released from adrenergic nerves by electrical stimulation or tyramine displacement were not different between arteries from normal and diabetic groups. Neuronal uptake blockade using cocaine caused a significantly smaller leftward shift in the contractions produced by electrical stimulation and exogenously applied noradrenaline in arteries from diabetic rabbits. The tonic, but not phasic, contractions caused by phenylephrine were larger in arteries from diabetic rabbits. Calcium-induced contractions caused by readdition of calcium to a calcium-free medium containing potassium (15 mmol.litre-1) were also significantly larger in arteries from diabetic rabbits. BAY K 8644, a calcium channel activator, caused an increase in calcium induced contractions and abolished the difference between the two groups. CONCLUSIONS: Although neurogenic contractions of diabetic carotid artery are normal, there is inefficient or reduced neuronal uptake as well as increased activity of calcium channels in the smooth muscle which increase contractions to alpha adrenoceptor agonists.
Authors: Mónica García; Asunción Morán; Elena Calama; Maria Luisa Martín; Mariette Barthelmebs; Luis San Román Journal: Br J Pharmacol Date: 2005-07 Impact factor: 8.739
Authors: C Burgdorf; D Richardt; T Kurz; S Adler; A Nötzold; E G Kraatz; H H Sievers; G Richardt Journal: Diabetologia Date: 2003-03-22 Impact factor: 10.122