ALTERED CARDIAC ADRENERGIC NEUROTRANSMISSION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

1 Functional alterations of the sympathetic neuroeffector junction of the left atria were studied in rats with streptozotocin-induced diabet es. 2 Eight to 12 weeks of diabetes resulted in a marked decrease in t he positive inotropic response of left atria to electrical field stimu lation (EFS). 3 The overflow of [H-3]-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 sensitivitie s of the left atria to exogenous noradrenaline and tyramine in diabeti c rats. The maximum positive inotropic response to these agents were s imilar in diabetic and control animals. 5 The left atrial content of n oradrenaline was not significantly changed in diabetic rats. The cocai ne-sensitive uptake of [H-3]-noradrenaline was also unaltered. 6 Atrop ine enhanced the positive inotropic response and [H-3]-noradrenaline o verflow induced by EFS in control left atria. Similarly, yohimbine cau sed an enhancement of EFS-evoked inotropic response in control atria. However, these effects of the antagonists were not observed in diabeti c left atria. 7 It is concluded that the decrease in the positive inot ropic response of the left atria to EFS in diabetic rats is caused by an impairment of noradrenaline release from the sympathetic nerve term inals through a calcium-dependent exocytotic mechanism. The present re sults also indicate that presynaptic alpha2-adrenoceptors and muscarin ic receptors that are linked to inhibition of the noradrenaline releas e during nerve stimulation may be functionally impaired in diabetic an imals.