Hitoshi Kontani

Sex differences in urethral pressure response to electrical stimulation of the hypogastric nerves in rats.

PURPOSE This experiment was performed to study the pharmacology of transmitters mediating the response, and the characteristics of the hypogastric nerve (HGN) of female rats, because electrical stimulation of the HGN was found to unexpectedly reduce urethral pressure in female rats. MATERIALS AND METHODS Male and female Wistar rats (weighing about 250 gm.), 10 weeks and 6 months old, respectively, were used under anesthesia. Fluid was infused from the bladder neck into the urethral lumen at a constant rate (0.5 ml./10 minutes), and infusion pressure signals were measured. Bilateral HGNs were electrically stimulated at 5 and 10 Hz for 30 s. RESULTS Electrical stimulation of the HGN reduced urethral infusion pressure in about 80% of the female rats, and the introduction of N(omega)-nitro-L-arginine methylester (L-NAME, 30 mg./rat, i.v.) elevated the urethral pressure response from a reduced state. Prazosin (0.1 mg./kg., i.v.) and hexamethonium (10 mg./kg., i.v.), which inhibited elevation of urethral pressure in male rats, also reversed and inhibited the elevation of urethral pressure in the female rats treated with L-NAME. CONCLUSION The HGN in female rats contained nerve endings that released nitric oxide (NO) and norepinephrine (NE). NO released during HGN stimulation inhibited the release of (NE) and reduced urethral infusion pressure in female rats. Nerves with synapses in the pelvic ganglia released NE in both male and female rats, but nerves that released NO did not have synapses in the ganglia. Only NE was released from the HGN nerve endings in male rats.

Urinary Bladder Response to Hypogastric Nerve Stimulation After Bilateral Resection of the Pelvic Nerve or Spinal Cord Injury in Rats

Background: We examined the mechanism of urinary bladder motility return after bladder areflexia induced by interruption of the sacral parasympathetic outflow to the urinary bladder following damage to the sacral cord or pelvic nerves in the rat.

Physico-chemical properties of oxybutynin

The dissociation constant, partition coefficient (octan-1-ol–water), solubility and stability of oxybutynin (OXY)in vitro were studied at 37 °C and an ionic strength of 0.15 using high-performance liquid chromatography. The dissociation constant was determined by potentiometry in methanol–water. The pKa value of 8.04 was extrapolated to 0% methanol concentration and agreed with that evaluated from the solubility. The apparent partition coefficients and the solubilities were measured at various pH values by means of the shaking method. The intrinsic partition coefficient for the non-ionized and ionized forms were determined as 7.8 × 104 and 5.0, respectively. The solubility was directly determined as 1.2 × 10–2 mg ml–1 for the free base of OXY and as 77 and 0.8 mg ml–1 at pH 1 and 6, respectively. In buffer of pH from 1 to 8, OXY is very stable and the degradation is almost negligible, whereas it is rapidly degraded at alkaline pH. The hydroxide ion catalysed rate constant is estimated to be 2.1 mol–1 l min–1; e.g., its half-life of degradation at pH 12.0 is 14 min.

Sex difference in urethral response to electrical stimulation of efferent nerves in the pudendal sensory branch of rats

Background: We reported sex difference in the urethral pressure (UP) response to electrical stimulation (ES) of the hypogastric nerve in rats. The purpose of the present study was to report on sex difference in the UP response to ES of the pudendal nerves (PN) in rats before and after injection of d‐tubocurarine (d‐tc).

Effects of nifedipine on bladder overactivity in rats with cerebral infarction

PURPOSE Our objective was to evaluate the effect of the calcium (Ca2+) channel blocking agent nifedipine on bladder overactivity induced by middle cerebral artery (MCA) occlusion and determine its site of action. MATERIALS AND METHODS Seven days after implantation of a bladder catheter, a cannula for intracerebroventricular and intrathecal administration was implanted and the left MCA was occluded with 4-0 monofilament nylon thread in male SD rats. Twenty-four hours after the induction of cerebral ischemia, saline was infused into the bladder at a constant rate (200 microL/min.) and cystometrogram was measured in conscious state. Nifedipine was administered intracerebroventricularly (5 microL) or intrathecally (20 microL) at graded doses (0.15 ng.-0.15 microg., 0.15 microg. -1.5 microg., respectively). RESULTS Bladder capacity in conscious rats was significantly reduced after the left MCA occlusion. Intracerebroventricular administration of nifedipine significantly increased bladder capacity in cerebral infarcted rats but not in sham operated rats. Furthermore there was no significant difference in bladder capacity between before and after intrathecal administration of nifedipine in cerebral infarcted rats. CONCLUSION These results show that Ca2+ channel blocking agents can operate especially on the supraspinal central nervous system rather than on the spinal system in rats with neurogenic bladder overactivity following cerebral infarction.

Central Muscarinic Receptor Subtypes Regulating Voiding in Rats

PURPOSE Muscarinic receptors are distributed widely in the brain. A recent study revealed that central muscarinic receptors are involved in voiding regulation. However, to our knowledge the role of each muscarinic receptor subtype has not been resolved. Therefore, we evaluated the effect of intracerebroventricular administration of selective muscarinic M1 to M4 receptor antagonists on voiding function in rats. MATERIALS AND METHODS Female Sprague-Dawley rats were cannulated for intracerebroventricular infusion under halothane anesthesia. In experiment 1 cystometry was performed in conscious rats, and BC and maximal voiding pressure were measured. In experiment 2 a catheter was inserted via the bladder dome to the bladder neck and UPP was measured by saline infusion. Repeat cystostomy was performed, and saline infusion and discharge saline, BC, maximal IVP and minimal UPP were measured in conscious rats. Pirenzepine, methoctramine, pFHHSiD and MT-3 were used as selective M1, M2, M3 and M4 muscarinic receptor antagonists, respectively, which were injected intracerebroventricularly. RESULTS In experiment 1 pirenzepine and pFHHSiD increased BC and decreased maximal voiding pressure. Methoctramine and MT-3 decreased BC. In experiment 2 pirenzepine and pFHHSiD increased BC and minimal UPP, and decreased maximal IVP. Methoctramine and MT-3 decreased BC and maximal IVP. Minimal UPP remained unchanged. CONCLUSIONS Intracerebroventricular administration of muscarinic M1 and M3 receptor antagonists inhibited urination in conscious rats, while M2 and M4 receptor antagonists induced excitatory changes.

Effect of nicotine on the pelvic afferent nerve activity and bladder pressure in rats

Objectives:  To record afferent nerve activity and bladder pressure in anesthetized male rats and to investigate whether increased afferent nerve activity induced by nicotine is able to evoke reflex bladder contractions.

Adsorption of bile acid by chitosan salts prepared with cinnamic acid and analogue compounds.

A chitosan (CS) powder treated with cinnamic acid and an analogue compound (CN) was prepared as CS-CN. Using it, bile acid adsorption by CS-CN and the release of CN were investigated in vitro. When CS-CN was soaked in a taurocholate solution, it released CN and simultaneously adsorbed the bile acid. For CS-CN prepared with cinnamic acid, the amount of CN released was 0.286 ± 0.001 mmol/g CS-CN; the amount of taurocholate adsorbed was 0.284 ± 0.003 mmol/g CS-CN. These two functions were recognized on alginate or pectin gel beads containing CS-CN. The amount of released CN was altered extensively by the species of CN used for gel-bead preparation. Results suggest that CS-CN is a candidate for complementary medicine to prevent lifestyle-related diseases.

High-performance liquid chromatographic preparation of oxybutynin enantiomers on a chiral stationary phase

Abstract A method for the preparation of oxybutynin enantiomers by high-performance liquid chromatography (HPLC) on a chiral stationary phase (Chiralpak AD) was

Comparison of the effects of percutaneous and intraduodenal administration of oxybutynin on bladder contraction and salivation in rabbits

Aim:  As only a few basic animal experiments have assessed the usefulness of percutaneous application of oxybutynin, we compared the effects of percutaneous application and intraduodenal injection of oxybutynin on urinary bladder contraction accompanied by micturition in conscious rabbits and salivation in anesthetized rabbits.