Effect of Pronethalol on Some Inhibitory Actions of Catecholamines

Abstract

On the blood pressure of the pithed rat isoprenaline produced a vasodepressor, noradrenaline a pressor, and adrenaline a biphasic response consisting of a rise followed by a fall in the pressure. The magnitude of the responses to increasing doses of adrenaline was not proportional to the doses. An intravenous injection of pronethalol (nethalide) hydrochloride (1 mg./kg.) changed the responses to adrenaline into purely pressor, well-graded responses; they were also increased. The responses to isoprenaline after pronethalol were reduced, but those to noradrenaline remained usually unaltered. Similar results were obtained in anaesthetised rats, rabbits and guinea-pigs, but the augmentation of the pressor effect of adrenaline was not so marked as in pithed rats. The vasodepressor action of dopamine in rabbits and guinea-pigs was not blocked by pronethalol (2·5 to 10 mg./kg.). The inhibitory actions of adrenaline, noradrenaline and isoprenaline on the isolated rat uterus and rabbit colon were not consistently antagonised by concentrations of pronethalol up to 1·0 μg./ml. In experiments on the rabbit duodenum and ileum, pronethalol, 0·2 to 1·0 μg./ml., reduced the relaxations produced by all three catecholamines. These results are discussed in relation to Ahlquist's theory of a dual adrenergic receptor mechanism.