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Addition of insulin to the organ bath increased the force of contraction of guinea‐pig left atrial strips driven electrically at 1 Hz The positive inotropic response to insulin remained unaltered in atria depleted of catecholamine or when β‐adrenoceptors were blocked by addition of propranolol to the organ bath The response of isolated atria to noradrenaline was significantly reduced in the presence of insulin Insulin affected neither the calcium accumulating abilities of the heart sarcolemma, mitochondria or microsomes, nor the cyclic adenosine 3′, 5′‐monophosphate (cyclic‐AMP)‐protein kinase‐induced stimulation of microsomal calcium uptake Addition of insulin to the organ bath enhanced significantly the ability of the cardiac tissue to take up [3H]‐noradrenaline as well as [3H]‐metaraminol. The activities of monoamine oxidase and catechol‐O‐methyl transferase were not changed after addition of insulin to homogenates of the heart The ability of insulin to facilitate uptake of noradrenaline would be expected to cause a decrease in the amount of the amine reaching the receptors, thus leading to a diminished response to this amine. This may explain, at least in part, insulin‐induced subsensitivity to noradrenaline This view is supported by the observation that after blockade of amine uptake by destruction of nerve terminals, insulin failed to reduce the positive inotropic response to noradrenaline.

Isolated, atropinized, rat atria exhibited positive inotropic responses to bretylium, guanothidine and tyramine. These responses were prevented by treatment of the animal with reserpine, or by addition of dichloroisoprenaline to the organ bath. The positive inotropic effects of these compounds on atria from reserpinized animals were restored by incubation of the tissue with noradrenaline. On the basis of these findings it is concluded that the cardiac stimulation by bretylium, guanethidine and tyramine involves the release of catechol amines. The usually reported increase in sensitivity of the myocardium from reserpinized animals to noradrenaline was not observed. The influence of bretylium and guanethidine on cardiac uptake and release of noradrenaline was also studied with the rat. Guanethidine decreased the concentration of catechol amines and inhibited the uptake of exogenous noradrenaline, while bretylium had no effect on either. The decrease in concentration of cardiac catechol amines produced by guanethidine was prevented by treatment of the animal with bretylium or with l-phenyl-2-hydrazinopropane (pheniprazine), a monoamine oxidase inhibitor.

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