The effects of forskolin and isoproterenol on contractile force and cyclic AMP levels were compared in smooth muscle strips from rabbit urinary bladder dome. Both of forskolin and isoproterenol produced the time- and the dose-dependent relaxation and the time-and the dose-dependent increases in cAMP levels. The relaxant response to forskolin caused more slowly than that to isoproterenol. The two agents caused almost the same relaxant responses at same concentration. However, cAMP levels induced by forskolin was much more than those induced by isoproterenol. These results that amounts of cAMP in urinary bladder don't correlate with the relaxation responses in urinary bladder smooth muscle strips suggest that some forms of functional compartmentalization of cAMP may exist in the urinary bladder.

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A new technique for simultaneously recording urethral closure pressure and cross sectional area profile is described. The cross sectional area of the urethra could be measured using the field gradient principle. The procedure was performed readily in male patients and the recordings can be graphically presented during measurement. A high degree of reproducibility using this method was obtained. Typical recordings of control subjects as well as patients with pathology were obtained using this technique. The results of this study show that the maximum urethral closure pressure obtained was 60.8+3.4mmHg and functional profile length, 4.8+0.4cm. Internal meatus cross sectional area was 0.67+0.04cm² and the minimum urethral cross sectional area was 0.12+0.02cm². This method has been shown to be readily applicable in measuring urethral closure pressure in males and can potentially be used as a tool of comparing the functional parameters of pressure with the anatomical value of diameter.

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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.

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Delayed gastric emptying in diabetic patients occurs with progress of autonomic neuropathy as one late complication. Delayed emptying is deeply correlated with poor glycemic control, due to imbalance between nutrients absorption and effect of exogenous insulin. AS-4370 is a newly developed prokinetic agent which has been reported to selectively activate motility of the upper gastrointestinal tract through enhancing acetycholine release from nerve terminals within the enteric mural plexus. In this study, we evaluated the effect of AS-4370 on gastric motility in diabetic patients with autonomic neuropathy. Eight diabetic patients with autonomic neuropathy (3 males and 5 females) with mean age of 56 years old (range 29-66) participated to this study after giving written informed consent. Gastric motility was evaluated by gastric emptying and electrogastrography. Gastric emptying study was done using ^99mTc-Tin colloid labeled omelet meal served with 2 slices of toast and 200 ml of milk. Electrogastrography was recorded from epigastric skin surface, for 30 minutes before and after meal each. AS-4370, 7.5 mg tid, was given for four weeks after basal recording of gastric motility studies. Following the 4-week treatment with AS-4370, gastric motility studies were repeated. For the motility studies after medication, drug was given 30 minutes before test meal. Gastric retention rate at 150 minutes in all patients were over 45% of upper limit of normal range in basal study with mean value of 69 ± 5%, which decreased significantly to 52±5%, with AS-4370 treatment (p<0.01). Gastric emptying speed, another parameter for gastric emptying also improved with medication. In electro-gastrographic studies, duration of 3 cpm waves (2.8-3.2 cpm waves) in 30 minutes both before and after meal increased with AS-4370 treatment. Though the decrease of pre-prandial glycemic level was insignificant, HbAl level decreased after treatment significantly. In conclusion, AS-4370 improved gastric dysmotility, both delayed gastric emptying and abnormality in electrogastrography, in diabetic patients with autonomic neuropathy and improved glycemic control.

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