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The effect of dopamine on the overflow of endogenous noradrenaline norepinephrine from the perfused rabbit heart evoked by sympathetic nerve stimulation



The effect of dopamine on the overflow of endogenous noradrenaline norepinephrine from the perfused rabbit heart evoked by sympathetic nerve stimulation



Naunyn Schmiedeberg's Archives of Pharmacology 305(2): 109-116



The effects of dopamine and 2 dopamine receptor antagonists (pimozide, flupenthixol) on the release of endogenous noradrenaline [norepinephrine] evoked by electrical stimulation of the postganglionic sympathetic nerves and their influence on cardiac performance were measured in isolated perfused rabbit hearts. Dopamine 0.2 .mu.M decreased noradrenaline overflow and ventricular tension development in response to nerve stimulation. Dopamine 2 .mu.M increased spontaneous noradrenaline output and tension development. The noradrenaline overflow in response to nerve stimulation was greatly enhanced. This action was only partly reversed by wash out of exogenous dopamine, indicating de novo synthesis and facilitated release of noradrenaline. Pimozide (approximately 1 .mu.M) and flupenthixol 5 .mu.M had no effect on noradrenaline overflow and cardiac performance. In the presence of cocaine 18.3 .mu.M dopamine 2 .mu.M decreased the overflow of noradrenaline. This effect was fully antagonized by flupenthixol which on its own neither influenced transmitter overflow nor antagonized the presynaptic inhibitory effect of oxymetazoline 0.38 .mu.M. In the rabbit heart dopamine apparently has an inhibitory effect on the release of endogenous noradrenaline which appears to be mediated by presynaptic dopamine receptors and which differs from the prejunctional .alpha.-adrenoceptor mediated negative feedback mechanism.

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Accession: 006642409

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