Analysis of the relative biomechanical effects of alpha 1 and alpha 2 antagonists in modifying the compliance of the prostate and micturition parameters of the hormonally manipulated male rat.

The potential of the alpha 1 and alpha 2 antagonists to modify prostate compliance, and micturition characteristics of rats with hormonally enlarged prostates was studied. Prostate growth was induced in Sprague-Dawley rats using dihydrotestosterone (DHT) and estradiol (E) by daily subcutaneous injections of DHT 1.25 mg/kg and E 0.25 mg/kg together with 0.1ml of sesame oil, as a vehicle, for a period of 3 weeks. A control group of six rats was used wherein the vehicle alone was administered. Dose levels of 3, 10, 30, and 300 micrograms/kg of alpha 1 or alpha 2 antagonist were given at weekly intervals to each of the groups defined above. Voiding characteristics, in terms of micturition frequency and volume per micturition, were measured and correlated with the pharmacological and hormonal stimulus. Prostate compliance and weight was evaluated in each of the groups after rats were terminated and the ventral prostate was dissected and removed in in toto. Compliance measurements were made using a new biosensor system which is based on the principle of detecting the shift in the resonance frequency of the biosensor produced by the hormones on the acoustic impedance of prostate. The results show that DHT and [DHT+E] significantly increased prostate weight and decreased prostate compliance. The alpha 2 antagonist atipamezole significantly increased the compliance of all prostates, including controls, while the alpha 1 antagonist did not alter the compliance. It is concluded that this alpha 2 antagonist is more effective than the prazosin in reversing the hardening effect of hormones on the prostate.