Pathologic Changes in the Accessory Sex Glands of Rats Treated with a Sympatholytic Hypotensive Agent (Losulazine)

Abstract

Groups of 25 male Sprague-Dawley rats were treated by gastric intubation with either vehicle control (modified methylcellulose) or a suspension of losulazine at 4, 8, 16, or 32 mg/kg/day for 1 yr. Ten rats/group were killed after 6 months of treatment. Reversibility of drug-induced changes was evaluated in 8 rats/group treated for 6 months and held without treatment for 5 months. Daily clinical signs and weekly body weight changes were monitored. Seminal vesicle/coagulating glands were weighed in rats treated for 6 months. Gross and microscopic evaluation of the accessory sex glands (ampullary glands, prostate, seminal vesicles and coagulating glands) was conducted in all rats killed at 6 months, after the recovery period, and in rats that survived through the one-yr treatment period. Ptosis, somnolence, and fecal softening were detected in all groups treated with losulazine. There was a nonreversible body weight gain retardation in groups treated with 8 to 32 mg/kg/day of losulazine for 6 months or 1 yr. Absolute and relative weights of the seminal vesicle/coagulating glands of treated rats were not significantly different from those of control rats. The ventral prostate in a few rats in all treated groups had yellow to tan granular foci. Treatment, but not dose-related sperm granulomas or glandular impaction with inspissated secretion (formation of corpora amylacia) in the ampullary glands, enhanced cellular exudation into the acini of the ventral prostate, and impaction of the seminal vesicles with altered granular to globular secretion were found in rats treated with losulazine. Exudative prostatic lesions were reversible and ampullary gland sperm granulomas were evident as resolving fibrotic areas 5 months after drug withdrawal. The pathologic changes seen in the accessory sex glands of rats treated with losulazine were considered to have been caused by ejaculatory stasis, apparently related to the sympatholytic effects of the drug on these organs.