Possible Role of Bladder Carbon Monoxide in the Regulation of Micturition Reflex in Rats

Objectives To clarify the roles of bladder carbon monoxide (CO), an endogenous gasotransmitter, in regulation of the micturition, we investigated the effects of a CO‐releasing molecule (CORM3) on the micturition and the contractility of bladder tissues in rats. We also examined expression levels of heme oxygenase (HO)‐1 and HO‐2, enzymes related to CO biosynthesis, in the rat bladder. Methods In urethane‐anesthetized (0.8 g/kg, ip) male Wistar rats, the effects of intravesically administered CORM3 (10 −8 , 10 −7 and 10 −6 M) on the micturition were investigated by continuous cystometry. The effects of CORM3 (1 × 10 −8 –3 × 10 −5 M) on the contractility of bladder strips pre‐contracted by carbachol (10 −5 M) were examined. Levels of mRNA of HO‐1 and HO‐2 in the bladder were investigated by real‐time polymerase chain reaction, and distribution of these isozymes in the rat bladder was immunohistochemically examined. Results Intravesical administration of CORM3 (10 −6 M) significantly prolonged intercontraction intervals without affecting maximal voiding pressure, baseline pressure or threshold pressure. In bladder tissue strips pre‐contracted by carbachol, CORM3 exhibited a slight relaxation effect, although the difference was not statistically significant compared with the vehicle‐treated control group. In the rat bladder tissues, HO‐1 and HO‐2 mRNA were detected. Immunoreactivity of both isozymes was mainly detected in the mucosal and muscle layers in the bladder, and HO‐2, but not HO‐1, was colocalized with β3‐tubulin, a neuronal marker. Conclusions Bladder CO has a possibility to inhibit the rat micturition independently of bladder smooth muscle relaxation and the rat bladder has a potential for endogenous CO production.