The Effect of Alpha-2 Agonists and Antagonisits on the Upper Urinary Tract of the Rat.

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We examined the effect of the selective alpha-2 agonist dexmedetomidine and antagonist atipamizole on the upper urinary tract, renal pelvic pressure and ureteral peristalsis. Experiments were performed on twelve Sprague-Dawley female rats weighing 275-323 grams, with administration of urethane (1.2μg/kg). Ventilatory support was provided through a tracheotomy. A continuous normal saline infusion was maintained through the left iliac vein at a rate of 2.5ml/hr. Arterial pressure was measured at the left iliac artery, which was cannulated with a PE-100 tube connected to a pressure transducer. A mid-line incision was then made from the xyphoid to the symphysis to expose the left kidney, both ureters, and the bladder. The bladder was intubated and drained to avoid bladder pressure increase. Measurements of urine output rate were made from the right ureter and renal pelvic or ureteral pressure was measured using a nephrostomy placed into the left pelvis. A ureterostomy was produced by introducing another catheter, into the upper segment of the left ureter for ureteral pressure measurements. The rats were divided into two groups as follows: 1) dexmedetomidine group (n=6); injected intravenously with 2μg/kg of dexmedetomidine dissolved in 0.5ml saline. 2) atipamizole group (n=6); injected intravenously with 2μg/kg of atipamizole dissolved in 0.5 ml saline. Ureteral peristaltic frequency, baseline pressure, and contraction amplitude were compared before, after, and between the bolus injections of 2μg/kg dexmedetomidine (n=6) or 2μg/kg atipamizole (n=6) in 0.5 ml saline. The results showed that dexmedetomidine at 2μg/kg produced a significant decrease in arterial pressure and an increase in urine output from 1.2+0.8 to 3.6+1.2ml/min. There was no effect on the baseline pelvic pressure of 6.8+1.2 cmH2O or amplitude of the renal pelvic contractions: 3.5+0.6cm H2O. The frequency of pelvic contractions was reduced from 0.37+0.03 to 0.27+0.02 Hz. Atipamizole at 2μg/kg produced a significant reduction in urine flow rate of 1.1+0.8 to 0.6+0.2ml/min. Atipamizole also showed no significant effects on baseline pelvic pressure or frequency, but increased the amplitude of pelvic contractions from control values of 3.0+0.9 to 3.4+0.9cm H2O. Dexmedetomidine reduced both the baseline ureteral pressure of 8.5+2.4 and peristaltic contraction pressure of 11.5+2.3cm H2O in 4/6 rats. Atipamizole reduced base-line ureteral pressure and increased peristaltic rate. This study has shown that dexmedetomidine has an inhibitory effect on renal pelvic contraction which is followed by weak excitatory effects of short duration. This effect is expressed by a decrease in the frequency of contractions and a decrease in the baseline pressure which was not significant statistically in view of the increased urine output. In contrast, atipamizole causes an excitatory effect on upper urinary tract contractility.
日本平滑筋学会の論文

The Effect of Alpha-2 Agonists and Antagonisits on the Upper Urinary Tract of the Rat.

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