Pharmacological preconditioning of ATP-sensitive potassium channel openers on acute urinary retention-induced bladder dysfunction in the rat

Objective To investigate whether ATP-sensitive potassium (K_ATP) channel openers prevent bladder injury after acute urinary retention (AUR) and subsequent catheterization for AUR (AURC) in the rat. Materials and Methods Eight-week-old male Sprague-Dawley rats were divided into five groups: a sham-operated control group, an AUR group, and three AUR groups treated with: nicorandil (10 mg/kg); cromakalim (300 Âμg/kg); or glibenclamide (5 mg/kg). AUR was induced by intravesical infusion of 3.0 mL of saline via cystostomy with simultaneous clamping of the penile urethra and, after 30 min of AUR, the bladder was allowed to drain for 60 min. After the experimental period, bladder function was assessed using organ bath techniques (carbachol and KCl), and by measuring tissue levels of 8-isoprostane, a marker of oxidative stress. The participation levels of K_ATP channel pores were investigated using ELISA and real-time PCR methods, respectively. The degree of apoptosis was estimated using the TUNEL method in the bladder smooth muscle and epithelium. Results The AURC group showed significantly decreased contractile responses to carbachol and KCl, and significant increases in tissue 8-isoprostane levels and apoptosis index in the epithelium compared with the control group. Nicorandil and cromakalim, but not glibenclamide, significantly prevented these AURC-induced alterations. The expressions of K_IR6.1 and K_IR6.2 mRNAs were significantly up-regulated by the induction of AURC. Nicorandil and cromakalim, but not glibenclamide, significantly up-regulated expressions of K_IR6.1 and K_IR6.2 mRNAs in the bladder compared with the AUR group. CONCLUSION Our data indicate that nicorandil and cromakalim, but not glibenclamide, prevent AURC-induced bladder dysfunction via activation of K_ATP channels, with a subsequent decrease in oxidative stress and decreased induction of apoptosis.