THE EFFECTS OF RESERPINE, GUANETHIDINE AND OTHER AUTONOMIC DRUGS ON FREE FATTY ACID MOBILIZATION INDUCED BY PHENTOLAMINE

¹ Department of Metabolic Chemotherapy, Experimental Therapeutics Research, Lederle Laboratories, American Cyanamid Company, Pearl River, New York

The hypothesis that peripheral catecholamines mediated the rises in free fatty acids resulting from phentolamine administration was investigated. Reserpine and guanethidine pretreatment of dogs or rats and, in addition, ergotamine in rats completely antagonized the increase in free fatty acids induced by phentolamine. Meprobamate, chlorisondamine, hexamethonium, iproniazid, bretylium, Dibenamine and dichloroisoproterenol were not capable of blocking the free fatty acid response under the conditions studied. In dogs both guanethidine and reserpine increased free fatty acid levels in blood when administered alone. Blood glucose levels in dogs declined following guanethidine; reserpine produced an equivocal rise. The transient hyperglycemic and more prolonged hypoglycemic effects of phentolamine in dogs were not altered appreciably by pretreatment with reserpine or guanethidine. The results strongly suggest that peripheral catecholamines play a major role in mediating the effects of phentolamine in fat metabolism.