Regional differences in nitric oxide-mediated relaxation of the rabbit sphincter of Oddi

Abstract

We studied the role of the l-arginine-nitric oxide (NO) pathway in non-adrenergic, non-cholinergic (NANC) relaxation of the rabbit sphincter of Oddi by recording changes in isometric tension in response to electrical field stimulation in two series of experiments. In a first set of experiments, biliary sphincters of Oddi removed from New Zealand white rabbits were placed horizontally in an organ bath containing oxygenized, buffered (pH 7.4) Krebs solution. Contractile responses of the whole sphincter to field stimulation were determined. In the second set of experiments, sphincter of Oddi was divided into two parts and the effects of field stimulation wewe studied separately on areas close to the duodenal papilla (area I) and areas close to the common bile duct (area II). In the whole sphincter of Oddi, field stimulation induced an initial twitch-like contraction followed by relaxation proportional to the number of stimuli (3 and 10 stimuli at 20 Hz, 50 V, 0.1 ms). The magnitude of the contractile responses was considerably reduced by 1 μM atropine, phentolamine and oxprenolol (NANC solution). Field stimulation produced dose-dependent contractions of both segments of sphincter of Oddi in response to the same protocol as used with whole sphincter of Oddi. However, preincubation with NANC solution produced monophasic relaxation in response to field stimulation in area I, whereas area II preparations such as the whole sphincter of Oddi respondend with contractions followed by minimal relaxations. Field stimulation failed to induce either contractions or relaxations in the presence of 1 μM tetrodotoxin. 30 μM N G - nitro- l- arginine methyl ester abolished NANC relaxation in area I, but did not influence significantly contractile responses of area II, or the whole sphincter of Oddi. l-Arginine but not d-arginine (both 3 mM) reversed the inhibitory effect of N G - nitro- l- arginine on NANC relaxation in area I. We conclude that (i) the l-arginine-NO pathways is involved in NANC relaxation of sphincter of Oddi segment close to the duodenal papilla and (ii) that there are regional differences in NO-mediated relaxation of the sphincter of Oddi in rabbits.