The Mode of Action of Irritants on the Granulopexy and the Dyestuff Permeability of the Cutaneous Vascular Endothelium

35 kinds of irritating substances in clinical uses were injected intracutaneously in the abdominal skin of the rat, and tested for the activities eliciting granulopaxy of carbon particles (India ink) and seepage of trypan blue, both injected intravenously, in the local cutaneous vascular endotheluim, by the methods previously described. Of these substances both actions were observed with the intensity of the descending order mentioned in the following: decylamine hydrochloride, croton oil, saponin, dextran, sodium cholate, ammonia, HgCl(2), arsenic trioxide, quinine hydrochloride, oil of sinapis, formaldehyde, xylene, ethylmorphine hydrochloride, morphine hydrochloride, formic acid, lactic acid, emetine hydrochloride, irgapyrin, diburaine hydrochloride, turpentine oil, chloroform, acetone, and tropacocaine hydrochloride. Saturated solutions of urethane, sodium chloride, potassium chloride and sodium sulfate likewise elicited these reactions. In the rat skin depleted of histamine by repeated injections of sinomenine, both of these reactions were inhibited to various degrees in the drugs other than urethane, sodium chloride and potassium chloride. This indicates that the actions of these substances are partially governed by histamine release. In the skin depleted of 5-HT by repeated injections of reserpine, actions of decylamine hydrochloride, croton oil, saponin, quinine hydrochloride, ethylmorphine hydrochloride, morphine hydrochloride, and irgapyrin was decreased. Therefore, these eight substances seem to liberate both histamine and 5-HT. In the rat given phenergan or sodium salicylate, the actions of histamine releasing substances were partially depressed. The actions of urethane, sodium chloride and potassium chloride solutions were partially inhibited only by cortisone. From these findings it is evident that in the actions of chemical substances that induce granulopexy and an increase in the dyestuff permeability in the cutaneous vascular endothelium an irritating mechanism other than the mediation by histamine and 5-HT release is contained. In all these active substances granulopexy paralleled with the increase in the dyestuff permeability. This suggests the involvement of a basic process common to the mechanisms of these two reactions.