Background. Nitric oxide (NO*) is an inhibitory neurotransmitter that induces sphincter of Oddi relaxation. Superoxide (O2/(·-)-scavenging enzymes are present in enteric plexuses of the sphincter of Oddi and O2/(·- ) alters sphincter of Oddi motor function. O2/(·-) rapidly oxidizes nitric oxide (NO*) to form peroxynitrite (ONOO-), thus terminating the biological activity of NO*. The aim of our study was to determine the effects of ONOO- on sphincter of Oddi motility in vitro. Materials and methods. Adult opossums were sacrificed and the sphincter of Oddi was removed and placed in a tissue bath containing oxygenated Krebs solution at 37°C. In the first series of experiments, force transducers recorded tension in a transverse orientation at two sites along the spontaneously contracting sphincter of Oddi. In a second series of experiments, circular muscle strips were precontracted with carbachol and stimulated by an electrical field. Results. ONOO-, superoxide dismutase (SOD), Nω-nitro-L-arginine (L-NNA), or oxyhemoglobin were added to the tissue baths. ONOO- decreased the frequency of contractions in the spontaneously contracting sphincter of Oddi. Adding hemoglobin increased the frequency of contractions. ONOO- also increased the stimulation-induced relaxation compared to controls. The increase in relaxation induced by ONOO- was inhibited by oxyhemoglobin and L-NNA but not SOD. Pretreatment with oxyhemoglobin prevented the increase in the stimulation-induced relaxation caused by ONOO-. Conclusion. These results suggest that hemoglobin binds ONOO- or that ONOO- generates NO.
- Sphincter of Oddi
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