THE EFFECT OF ESTRIOL-16,17-DIHEMISUCCINATE ON VASCULAR PERMEABILITY AS EVALUATED IN THE RAT PAW OEDEMA TEST

Abstract

On the basis of previous findings it was suggested that estriol-16,17-dihemisuccinate might counteract the development of induced local oedemas. To test this assumption, a study was performed using the rat paw edema test. Depending on the material used, three types of edema could be produced Rapid and transient type, when serotonin, histamine, compound 48/80, chicken egg white and polyvinylpyrrolidone were the indueers. Slow and long lasting type, with kaolin as inducer. Rapid and long lasting type when cobra venom served as inducer. Cyproheptadine inhibited the rapid and transient type of oedema, except when polyvinylpyrrolidone was used. Furthermore cyproheptadine counteracted the rapid phase of the oedema produced by cobro venom, but did not influence the slow and long lasting oedema induced by kaolin or the delayed phase of the cobra venom edema. Phenylbutazone counteracted the slow and long lasting swelling induced by kaolin and the delayed phase of swelling induced by the snake venom, but exerted no effect on any rapid and transient edema, or on the early phase of edema produced by snake venom. Estriol-16, 17-dihemisuccinate did not selectively inhibit any one kind of edema more than another, but counteracted at approximately equal potency all the types of edema studied. Cyproheptadine and phenylbutazone possibly exerted their edema inhibitory effect at the level of the initiating mechanisms, such as eg. by antagonizing the effect of liberated serotonin or by counteracting some as yet undefined process(es) involved in inflammation. The non-selective inhibitory action of estriol-16,17-dihemisuccinate suggests this drug may have counteracted the edemas at the level of vessel permeability, a common factor in all local types of oedemas, irrespective of their initiating mechanism. The experiments presented here appear to justify the correctness of the original assumption and provide further evidence for the frequently postulated vascular mechanism underlying the antihaemorrhagic effect of estriol-16,17-dihemisuccinate.