THE EFFECT OF ALPHA2 AGONISTS AND ANTAGONISTS ON THE LOWER URINARY-TRACT OF THE RAT

The pharmacologic potential of selective alpha2 adrenergic agents in modulating vesicourethral function was evaluated in urethane-anesthetized and conscious rats. The bladder was exposed through a midline incision and intubated via a cystostomy to measure pressure. The bladder was filled with saline at 0.05 ml./min. In six animals intravenous dexmedetomidine 0.6 mug./kg. followed by 2 mug./kg. was given. In another six rats the infusion was made with atipamezole at the same concentration. The parameters obtained were pressure/volume during cystometry, detrusor voiding pressures, and evidence of urine leakage. Conscious rats were placed in a restrainer outfitted with a voided volume sensor and a data recorder. The animals were divided in three groups. In controls, group I (n = 8), the animals were injected with a subcutaneous (SC) load of 5 ml. saline in which furosemide 10.0 mg./kg. was added. In group II (n = 6), dexmedetomidine was added, in group III (n = 6), atipamezole was added. Parameters obtained were volume per micturition, latency, frequency of micturition, and patterns of micturition (such as dribbling), and total volume produced after a three hour recording. Values are expressed as mean +/- standard deviation. The results show that in an anesthetized preparation, the alpha2 agonist dexmedetomidine produced inhibitory effects on the volume evoked micturition reflex (VEMR) at a dose level of 2.0 mug./kg. There was a significant decrease in peak pressure from 26.4 +/- 3.6 to 6.8 +/- 2.1 cm. H2O (P <0.01). Urine leakage was observed at the external meatus. Atipamezole, the alpha2 agonist, gradually increased bladder baseline pressure and inhibited VEMR. At a critical pressure there was continuous leakage from the external meatus. There was a significant elevation of baseline bladder pressure by atipamezole from 6.3 +/- 1.7 to 29.8 +/- 4.6 cm. H2O (p <0.005). In conscious rats, the alpha2 agonist produced urinary dribbling at almost-equal-to 20 minutes after SC injection, while the antagonists produced delayed dribbling 70 minutes after SC injection. Leakage occurred in 3 of 6 rats at a dose of 10 mug./kg. of atipamezole and in 5 of 6 rats at a dose of 30 mug./kg. The alpha2 agonist caused a diuretic effect and a dose-dependent increase in the frequency of voiding (p <0.05), while the antagonist decreased the frequency of voiding. Bladder capacity was decreased with the alpha2 agonist while the antagonist increased capacity.