Cardiovascular effects of copper in pithed rats

The pithed rat preparation was used to study the effects of copper (as cupric chloride) on the release and re-uptake of noradrenaline from sympathetic nerves. At the highest concentration which could be tested without failure of the preparation, there was a slight prolongation in the duration of the tachycardia obtained by electrical stimulation of the cardioacceleratory nerves to the heart. However, the tachycardia obtained after intravenous injection of tyramine was also similarly prolonged from which it is concluded that the phenomenon is not related to inhibition of neuronal re-uptake but is more likely due to alterations in the metabolism of noradrenaline or in the factors governing its diffusion from the synapse. Copper itself caused a dose-dependent increase in blood pressure which was not due to release of noradrenaline from sympathetic neurones. In addition to its own vasoconstrictor effect, it inhibited the increase in blood pressure obtained after administration of phenylephrine, tyramine and vasopressin. Since the extent of the inhibition of all three compounds was similar, it is concluded that the effect is non-specific inhibition of blood vessel contractility. In the pithed rat preparation, as in the chick biventer preparation (Lin-Shiau & Fu 1980), the acute effects of copper seem to be more clearly seen on muscle with little evidence being available to support potent neurotoxicity.