The effect of alpha 2 agonists and antagonists on the lower urinary tract of the rat.
The pharmacologic potential of selective alpha 2 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 micrograms./kg. followed by 2 micrograms./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 alpha 2 agonist dexmedetomidine produced inhibitory effects on the volume evoked micturition reflex (VEMR) at a dose level of 2.0 micrograms./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 alpha 2 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 alpha 2 agonist produced urinary dribbling at approximately 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 micrograms./kg. of atipamezole and in 5 of 6 rats at a dose of 30 micrograms./kg. The alpha 2 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 alpha 2 agonist while the antagonist increased capacity.
Harada
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Spinal Cord Injury Service, Department of Veterans Affairs, Stanford, California.
Constantinou
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D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D020926:Medetomidine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014521:Urethra / Q000187:drug effects* / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D014554:Urination / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole; D020926:Medetomidine