Inhibition of the edema of paraphenylenediamine by drugs and relationship of the adrenals.

Abstract

In a previous study, the mechanism of edema formation in rabbits and cats receiving paraphenylenediamine was found to be concerned with a marked increase in vascular permeability, independently of nerve connections, in the head and neck regions 1 This report deals with a short summary of results on the nicotine inhibition, and certain other features.

The edema has been prevented in 70 per cent of 27 rabbits and cats by nicotine (5.6 to 26 mg. per kilo subcutaneously, or 1.4 to 14.7 mg. per kilo intravenously in divided doses). In the remainder, it has been retarded or not inhibited at all, for reasons which may be apparent from the results on adrenal relationship. The nicotine dosage employed did not cause paralysis of the sympathetic and parasympathetic ganglia. The inhibition was not concerned with the Gasserian ganglia and any hypothetical peripheral synapses in the edema organs, since the edema occurred after local infiltration with, and application of, nicotine, and also after degeneration of these structures. Nicotine did not inhibit the edema of the perfused head and extremities. Hence, the inhibition appeared to be systemic. It was not concerned with circulatory depression, for a high degree of circulatory efficiency was maintained throughout. Since the continuous intravenous injection of epinephrine and reduced blood flow to the head also inhibit the edema (Tainter and Hanzlik 1 ), as does continued stimulation of the cervical sympathetic nerves (Gibbs), a similar mechanism, namely, vasoconstriction, resulting in reduced blood flow to the head, was suggested for the nicotine inhibition. This could occur through the adrenals, that is, by increased epinephrine output of these glands in virtue of the nicotine, a well-known action of this poison.

The dosage of nicotine used increased the output of epinephrine as indicated by the cava pocket method of Stewart and Rogoff 2 in cats, and by the denervated and atropinized pupil of Meltzer 3 in cats and rabbits, the latter method being chiefly employed, and the pupillary response to epinephrine previously determined.