Effect of Noradrenaline, Bretylium and Cocaine on the Blood Pressure Response to Tyramine in the Rat

Abstract

Tyramine is mainly a pressor agent in the rat under urethane, although the hypertensive effect of tyramine in some experiments is followed by a prolonged increase or depression of blood pressure. Bretylium, in doses up to 10 mg/kg, prolonged the response to tyramine, whereas larger doses depressed or blocked its effect. When the hypertensive effect of tyramine was blocked by bretylium, both noradrenaline and dihydroxyphenylalanine, when slowly infused, were found to restore it. The well-known block by cocaine of the hypertensive response to tyramine could also be reversed by intravenous infusion of noradrenaline and dihydroxyphenylalanine. It is concluded that the infusion of noradrenaline and dihydroxyphenylalanine makes available noradrenaline in the postganglionic adrenergic nerves which is necessary for the action of tyramine.In spinal preparations made from cats previously treated with reserpine, tyramine and many other sympathomimetic amines which are not derivatives of catechol lose their pressor action. This action can be restored in the reserpine-treated animal by an infusion of noradrenaline (Burn & Rand, 1958a). These observations suggest that tyramine and similar substances normally act by releasing noradrenaline or adrenaline from the arterial walls. In fact it has been shown that under certain conditions intravenous injections of tyramine increase the concentrations of adrenaline and noradrenaline in a sample of plasma withdrawn from the lower aortae of cats under chloralose.Tyramine is also classified as a sympathomimetic substance acting on postganglionic adrenergic nerve fibres because it does not act on denervated effector organs (Burn & Tainter, 1931;Fleckenstein & Burn, 1953). Bretylium is found to depress conduction of impulses in adrenergic neurones with subsequent failure of noradrenaline and adrenaline release, leaving at the same time intact the adrenergic receptors of the effector cell (Boura & Green, 1959). It was therefore of interest to investigate the effect of bretylium on the vascular response to tyramine. It was expected that the effect of tyramine would be particularly easy to -block if this substance acted primarily on the postganglionic adrenergic fibres. This work was started in order to investigate the site and mechanism of action of tyramine in causing changes of blood pressure in the rat. The experiments with bretylium were compared with the results obtained with cocaine in order to show their similar modes of action.