PROMOTION BY THE ALPHA-ADRENOCEPTOR AGONIST PHENYLEPHRINE, BUT NOT BYTHE BETA-ADRENOCEPTOR AGONIST ISOPROTERENOL, OF GASTRIC CARCINOGENESIS INDUCED BY N-METHYL-N'-NITRO-N-NITROSOGUANIDINE IN WISTAR RATS

The effects of prolonged administration of the alpha-adrenoceptor agon ist phenylephrine and the beta-adrenoceptor agonist isoproterenol on g astric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine and on the labeling index of gastric mucosa were compared in Wistar ra ts. Rats received subcutaneous injections of 3 or 6 mg/kg body weight of phenylephrine or 0.1 or 0.2 mg/kg body weight of isoproterenol ever y other day after 25 weeks of oral treatment with the carcinogen. Long -term administration of phenylephrine at a high dose, but not at a low dose, significantly increased the incidence of gastric cancers and th e labeling index of antral epithelial cells at the end of the experime nt in week 52. However, administration of isoproterenol at either dosa ge had no significant effect on the incidence of gastric cancers and t he labeling index of antral epithelial cells. These findings indicate that increased activity of the sympathetic nervous system enhances gas tric carcinogenesis through alpha-adrenoceptors. (C) 1998 Elsevier Sci ence Ireland Ltd.