Morphometric and biochemical analysis of adrenal medullary hyperplasia induced by nicotine in rats.

The administration of nicotine (1 and 4 mg/kg/day, subcutaneously for up to 6 weeks) to male Sprague-Dawley rats first induced a time-and dose-dependent increase in catecholamine (CA) synthesis. This was followed by an increase in endogenous CA levels and in total volume and number of chromaffin cells, as measured by stereological methods on serially sectioned adrenal glands. Thus, continued stimulation of the sympathoadrenal system generated an increase in biosynthetic enzyme activity, and subsequently adrenal medullary hypertrophy and hyperplasia developed as an adaptive reaction. The proposed model is useful for quantifying both biochemically and morphometrically early adrenal changes long before irreversible pathologic alterations are manifested.