We have confirmed that hydrogen sulfide (H 2 S) is a possible relaxation factor in the rat bladder, and H 2 S-induced bladder relaxation is impaired in 18-week-old (18W) spontaneously hypertensive rats (SHRs), which show bladder dysfunctions. We compared effects of NaHS and GYY4137 (H 2 S donors) on bladder contractility and micturition reflex, and H 2 S contents and expression of enzymes related to H 2 S biosynthesis (CBS, MPST and CAT) in the bladder between 12W and 18W male SHRs. Effects of NaHS (1×10-8 to 3×10-4 M) were evaluated on carbachol (10-5 M)induced pre-contracted bladder strips. Under urethane-anesthesia, effects of intravesically instilled GYY4137 (10-8 to 10-6 M) on the rat micturition reflex were examined. The H 2 S contents and expression of CBS, MPST and CAT were measured by methylene blue method and western botting. Compared to 12W SHRs, NaHS-induced maximal relaxation of bladder strips was significantly decreased, GYY4137-induced intercontraction intervals prolongation was attenuated, the bladder H 2 S content and expression level of CBS, MPST and CAT in the bladder dome was higher in 18W SHRs. These results indicate that H 2 S-induced bladder relaxation in SHRs is impaired time-dependently, suggesting that early intervention in SHRs with H 2 S donors may prevent the development of hypertension-mediated bladder dysfunctions.

To clarify roles of brain cannabinoid CB 1 receptors in regulation of the micturition, we examined the effects of intracerebroventricularly (icv) administered rimonabant (Rimo, a CB 1 antagonist) and JZL195 (JZL, an inhibitor of enzymes related to degradation of endogenous CB receptor ligands) on icv administered bombesin (BB, a stressrelated neuropeptide)-induced facilitation of the micturition in urethane-anesthetized (0.8 g/kg, ip) male Wistar rats. A catheter was inserted into the bladder to perform cystometry. Three hours after the surgery, JZL (10 or 30 nmol/rat) or Rimo (100 or 300 nmol/rat) was icv administered 30 min before BB administration (0.01 or 0.03 nmol/rat, icv). BB (0.03 nmol) shortened the intercontraction interval (ICI), an indicator of micturition frequency, while JZL significantly suppressed the BB-induced response. BB at a lower dose (0.01 nmol) showed no significant effect on ICI, while the BB significantly shortened ICI after pretreatment with Rimo. In addition, JZL-induced suppression of the BB (0.03 nmol)-induced response was abolished in the presence of Rimo. These results indicate that brain CB 1 receptors suppress the centrally administered BB-induced facilitation of the rat micturition.

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