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Isolated spontaneously beating atria from streptozocin diabetic rats were compared with those from controls. Diabetic atria were found to have reduced rates, increased forces of contraction and reduced sensitivity to the inotropic effects of noradrenaline, isoprenaline, tyramine and calcium. Positive chronotropic responses to tyramine were also reduced but those to noradrenaline and isoprenaline were increased suggesting that tyramine releasable stores of noradrenaline were reduced. Elevation of glucose concentration in the medium from 5·6 to 27 min resulted in a decrease of inotropic sensitivity to the agents used in both control and diabetic rat atria. Resting contractile force of control rat atria was reduced by the inclusion of either 22 niM 2‐deoxyglucose, 10−3 i.u. insulin ml−1 or 5 mM acetate in the medium. The rate was also reduced by medium containing 2‐deoxyglucose but increased by insulin. 2‐Deoxyglucose also reduced inotropic but increased chronotropic sensitivity to isoprenaline. Possible mechanisms responsible for the changes observed are discussed.

I The sensitivities of alloxan and streptozotocin diabetic and hereditary obese pithed rats to acetylcholine, isoprenaline and noradrenaline were compared to those of controls. 2 Blood pressure and heart rate recordings made before dosing was started showed the streptozotocin-treated animals to have a significantly reduced heart rate and increased pulse pressure as compared with controls.3 Both diabetic groups were found to have reduced sensitivities to the pressor effect of noradrenaline, the depressor effect of acetylcholine, the positive chronotropic and inotropic effect of isoprenaline and the reduction in diastolic pressure induced by isoprenaline. The reduction in sensitivity was generally much greater in the streptozotocin diabetic animals. 4 The genetically obese rats were found to have similar sensitivities to all three agents as did their non-obese litter mates. 5When either diabetic group was deprived of food for 24 h preceding the tests the sensitivities were found to be raised significantly towards normal in almost all cases. 6 The results are contrasted with previous in vitro results and possible causative metabolic factors discussed. It is suggested that sensitivity changes are unevenly distributed within the cardiovascular system.

1 Atria, isolated from control rats, six-week streptozotocin-diabetic rats and from similarly diabetic rats treated with myo-inositol (MI) were compared. The MI treatment was shown to reverse the depressed sciatic nerve MI which was observed in the untreated diabetic group. 2 Spontaneously beating atria from the untreated diabetic animals beat more slowly, and with greater force than tissues from the control group. When electrically driven at 4 Hz they were found to be less sensitive to the negative inotropic effect of acetylcholine. No differences between the two groups were observed in responses to isoprenaline. 3 Intramural nerve stimulation in the presence of 10-6M propranolol (vagal stimulation) had a greater negative inotropic effect in the untreated diabetic rat atria than in the controls. Positive inotropic responses to nerve stimulation in the presence of 10-6 M atropine (sympathetic stimulation) were not significantly different between the two groups. 4 Atria from the MI-treated diabetic animals were found to have a lower spontaneous contractile force and greater sensitivity to acetylcholine than tissues from the untreated diabetic animals. The values obtained in both cases were similar to those from the controls. No significant effect of MI treatment on spontaneous contractile rate or on responses to nerve stimulation was demonstrated. 5 Atrial (mainly myocardial) MI was measured in additional control, six-week diabetic and six-week MI-treated diabetic animals. A significantly higher concentration was observed in the MI supplemented group compared to the untreated diabetic group. The mean MI content in the latter group was lower than that obtained from control tissues but not significantly so. 6 The results implicate MI depletion either in the neurones or in the myocardium in at least some of the changes observed. Possible mechanisms involved are discussed.

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