title: Altered cardiac adrenergic neurotransmission in streptozotocin-induced diabetic rats.
abstract: 1. Functional alterations of the sympathetic neuroeffector junction of the left atria were studied in rats with streptozotocin-induced diabetes. 2. Eight to 12 weeks of diabetes resulted in a marked decrease in the positive inotropic response of left atria to electrical field stimulation (EFS). 3. The overflow of [3H]-noradrenaline from diabetic left atria caused by EFS was much less than that from control preparations. 4. The concentration-response curves showed no change in sensitivities of the left atria to exogenous noradrenaline and tyramine in diabetic rats. The maximum positive inotropic response to these agents were similar in diabetic and control animals. 5. The left atrial content of noradrenaline was not significantly changed in diabetic rats. The cocaine-sensitive uptake of [3H]-noradrenaline was also unaltered. 6. Atropine enhanced the positive inotropic response and [3H]-noradrenaline overflow induced by EFS in control left atria. Similarly, yohimbine caused an enhancement of EFS-evoked inotropic response in control atria. However, these effects of the antagonists were not observed in diabetic left atria. 7. It is concluded that the decrease in the positive inotropic response of the left atria to EFS in diabetic rats is caused by an impairment of noradrenaline release from the sympathetic nerve terminals through a calcium-dependent exocytotic mechanism. The present results also indicate that presynaptic alpha 2-adrenoceptors and muscarinic receptors that are linked to inhibition of the noradrenaline release during nerve stimulation may be functionally impaired in diabetic animals.
authors.affiliation: Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Gando
authors.forename: Y
authors.initials: Y
authors.lastname: Hattori
authors.forename: M
authors.initials: M
authors.lastname: Kanno
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation*; D006325:Heart Atria / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009451:Neuroeffector Junction / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology*; D014439:Tyramine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D010656:Phenylephrine; D015016:Yohimbine; D001285:Atropine; D009638:Norepinephrine; D014439:Tyramine