The effect of peroxynitrite on sphincter of Oddi motility

Background Nitric oxide (NO.) is an inhibitory neurotransmitter that induce s sphincter of Oddi relaxation. Superoxide (O-2(.-))-scavenging enzymes are present in enteric plexuses of the sphincter of Oddi and O-2(.-) alters sp hincter of Oddi motor function. O-2(.-) 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 sphinct er 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 so lution at 37 degrees C. In the first series of experiments, force transduce rs recorded tension in a transverse orientation at two sites along the spon taneously contracting sphincter of Oddi. In a second series of experiments, circular muscle strips were precontracted with carbachol and stimulated by an electrical held. Results. ONOO-, superoxide dismutase (SOD), N-omega-nitro-L-arginine (L-NNA ), or oxyhemoglobin were added to the tissue baths. ONOO- decreased the fre quency of contractions in the spontaneously contracting sphincter of Oddi. Adding hemoglobin increased the frequency of contractions. ONOO- also incre ased 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 sti mulation-induced relaxation caused by ONOO-. Conclusion. These results suggest that hemoglobin binds ONOO- or that ONOO- generates NO. (C) 1999 Academic Press.