Influence of adrenoceptor blockade on endotoxin-induced histopathological changes in murine Meth A sarcoma

Histological examination of subcutaneous murine Meth A sarcomata 4 h after administration of endotoxin revealed an overt but superficial vasodilation, which had largely disappeared after 24 h. At this time hemorrhagic necrosis could be observed in that region mainly featured by degenerating tumour cells, diffuse hemorrhage and blood vessels filled with a yellow substance probably derived from disintegrated erythrocytes. Administration of the alpha-adrenoceptor antagonist phenoxybenzamine or the beta-adrenoceptor antagonist propranolol caused decrease of vasodilation at 4 h but an increase at 24 h especially after phenoxybenzamine. Only the latter agent prevented the induction of hemorrhagic necrosis by endotoxin. Endotoxin reduced tumour size within 24 h, which was prevented by both adrenoceptor blocking agents. Administration of these agents alone even enhanced tumour size. Mitotic activity of Meth A sarcoma was greatly reduced already 4 h after endotoxin injection. This was not significantly changed by both adrenoceptor antagonists, while these agents alone probably stimulate tumour cell division between 4 and 24 h after administration. The histological data are discussed in relation to earlier data on the influence of adrenoceptor blockade on endotoxin-induced hemorrhagic necrosis and tumour regression.