Optimal conditions to induce rat adrenal medullary changes, such as pheochromocytoma, by nicotine.
BACKGROUND
Nicotine-induced adrenal medullary hypertrophy in rats has been suggested to be a model for pheochromocytoma. Study conditions for proving such an assertion, however, have not been optimized.


METHODS
Studies on strain difference, dose dependency, and the time course of catecholamine metabolism in response to nicotine treatment were conducted. Under the putative optimal experimental conditions, metabolic and histologic changes in the adrenal medulla were investigated.


RESULTS
Male Wistar rats treated with a maximum dose of 4 mg/kg per day of nicotine for 9 weeks, including a 2-week lead-in period, developed highly consistent changes in the adrenal medulla. Concerning metabolic indices, the norepinephrine content of the adrenal and the urinary excretion of epinephrine and metanephrine were significantly elevated. Hyperplastic and hyperactive states of the adrenal medulla were also indicated by a morphometric analysis on electron microscopic figures. These showed an enlarged cytoplasmic area, the development of a rough-surfaced endoplasmic reticulum, and an increased number and density of intracellular catecholamine granules. The metabolic changes were found to reverse 3 weeks after the cessation of nicotine administration.


CONCLUSIONS
These results provide better-defined experimental conditions for an animal model of pheochromocytoma.
Saiko
Y
Y
Department of Urology, Faculty of Medicine, The University of Tokyo, Japan.
Homma
Y
Y
Kawabe
K
K
Aso
Y
Y
D000313:Adrenal Medulla / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology*; D000818:Animals; D002395:Catecholamines / Q000032:analysis / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006984:Hypertrophy; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D010673:Pheochromocytoma / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013997:Time Factors
D002395:Catecholamines; D009538:Nicotine