Irreversibility of methylandrostenediol-induced hypertension in the rat after suspension of the androgen treatment.

Administration of 10 mg of methylandrostenediol for 10 weeks to uninephrectomized, salt drinking, female Sprague Dawley rats caused severe hypertension with extensive renal and cardiovascular damage. The hypertension was accompanied by increased consumption of sodium, high sodium levels in peripheral plasma, decreased weight of the pituitary, thymus, adrenals and ovaries and decreased content of renal renin. Methylandrostenediol treatment also produced impairment of normal adrenal steroidogenesis, reflected in elevated production in vitro of 11-deoxycorticosterone during incubation of adrenal gland homogenates with (14)C-progesterone. Such increased production of deoxycorticosterone is probably responsible for the development of the hypertensive disease. If the methylandrostenediol-treated animals were kept alive for 12 additional weeks after suspension of the treatment with the androgen, the hypertension, as well as the high sodium consumption, high plasma sodium concentrations and low levels of renal renin, persisted to the end of the experiment. The cardiovascular and renal lesions in these animals, killed 12 weeks after suspension of the androgen administration, were similar to those seen in the rats receiving methylandrostenediol but killed at the tenth week of the treatment. Suspension of methylandrostenediol administration, however, resulted in a return to normal weight of the pituitary, thymus, adrenals and ovaries within 12 weeks. Normal amounts of deoxycorticosterone were formed in vitro by the adrenal glands of these rats and the return to normal structure was also confirmed by a electron microscopic study. Thus, contrary to a previous experiment where methylandrostenediol was given for a shorter period of time and the hypertension was reversible, it was shown in this study that metacorticoid hypertension is induced by methylandrostenediol administration, as it is with treatment with deoxycorticosterone. Since adrenal steroidogenesis returned to normal, some other mechanisms must be involved in maintaining the hypertension. It is very likely that these factors are consequent to the extensive and irreversible renal and cardiovascular damage.