Effects of NO/L-arginine pathway on gallbladder contractility in bile duct ligated guinea pigs

Common bile duct ligation (CBDL) produces gallbladder distension and acute inflammation similar to that seen in human acute acalculous cholecystitis. CBDL in the guinea pig affects smooth muscle contractility. The aim of this study was to determine whether the nitric oxide-L-arginine pathway plays a role in the inflammatory process and abnormal gallbladder contractility that occur after CBDL.

Contractility of gallbladder muscle from CBDL and sham-operated guinea pigs was studied in vitro. Animals were treated with saline, aminoguanidine (AG), or an aminoguanidine + L-arginine combination (AG + L-Arg) in vivo. Potassium chloride, carbachol, and electric field stimulation (EFS) were used for contracting the gallbladder muscle strips or activating intrinsic nerves. Hematoxylin and eosin-stained slides of muscle strips were scored for inflammation.

Contraction responses to carbachol and EFS were decreased significantly in CBDL guinea pigs compared with those in the sham-operated group. AG partly reversed the smooth muscle contractile response to carbachol and EFS, but did not reduce the inflammation score. Treatment with AG + L-arg did not reverse either the contraction response or the inflammation score.

These findings suggest that AG and AG + L-Arg treatments have no beneficial effect on inflammation in guinea pigs after CBDL, although AG significantly reversed the effect on muscle contractility (P < 0.05). This improvement was independent of inflammation and may be due to a decreased level of NO and its diminished relaxant effect.