Effect of exogenous H2S and ATP-sensitive potassium channels on colonic hypermotility in a rat model of chronic stress

AIM: To investigate the potential role of exogenous hydrogen sulfide (H₂S) and ATP-sensitive potassium (K_ATP) channels in chronic stress-induced colonic hypermotility.METHODS: Male Wistar rats were divided into water avoidance stress (WAS) group and sham WAS (SWAS) group. Organ bath recordings were used to test the contractile activity of colonic strips. The effects of H₂S donor NaHS and pretreatment with glibenclamide on the contractions of colonic smooth muscle were studied and the IC₅₀ of NaHS was calculated. The localization and expression of the subunits of K_ATP channels were determined by the methods of immunohistochemistry and Western blotting.RESULTS: WAS increased contractile activity of colonic strips. NaHS concentration-dependently inhibited the spontaneous contractions of strips from the SWAS and WAS rats. The IC₅₀ of NaHS for longitudinal muscle (LM) and circular muscle (CM) of the WAS rats was 0.2033 mmol/L and 0.1438 mmol/L, significantly lower than those of the SWAS rats. Glibenclamide significantly increased the IC₅₀ of NaHS for LM and CM from the SWAS and WAS rats. In both SWAS and WAS rat colon, Kir6.1, Kir6.2 and SUR2B were expressed on the plasma membrane of the smooth muscle cells. WAS treatment resulted in up-regulation of the expression of Kir6.1 and SUR2B in the colon devoid of mucosa and submucosa.CONCLUSION: The increased expression of Kir 6.1 and SUR2B in colonic smooth muscle cells may be a defensive response to chronic WAS. H₂S donors may have potential clinical effect on treating chronic stress-induced colonic hypermotility.