Mechanism of anestrus in rats treated with an antihypertensive agent, losulazine hydrochloride

The mechanism of anestrus in rats treated with losulazine, a peripheral sympatholytic antihypertensive agent, was investigated by determining its effect on hypothalamic catecholamines and serum sex hormones and by evaluating the influence of bromocriptine on the reproductive functions of rats treated with losulazine. Groups of six female Upjohn Sprague-Dawley rats were treated orally with 10 mg/kg/day of losulazine and/or 18.75 mg/kg/day of bromocriptine for 15 or 27 days. Six rats were treated with losulazine plus 6.25 mg/kg/day of bromocriptine for 16 days followed by losulazine alone for 11 days. Rats treated with losulazine only were depleted of hypothalamic catecholamines, were hyperprolactinemic, and had interrupted estrous cycles and attenuated vaginal mucosa. Treatment with bromocriptine, a dopamine receptor agonist, resulted in suppression of serum prolactin and normal estrous cycles. Rats reverted back to hyperprolactinemia and anestrus shortly after bromocriptine withdrawal. These results suggest that hyperprolactinemia mediated through hypothalamic dopamine depletion is the mechanism of anestrus in rats treated with losulazine.