Effects of recombinant human hemoglobin on opossum sphincter of Oddi motor function in vivo and in vitro

Digestive Diseases and Sciences
J J CullenG Rosenthal

Abstract

Nitric oxide (NO) acts as a nonadrenergic, noncholinergic inhibitor neurotransmitter that regulates sphincter of Oddi (SO) motor function. Hemoglobin blocks NO activity by binding it after it is synthesized. We hypothesized that recombinant human hemoglobin (rHb1.1) affects SO motor function by scavenging NO. Under anesthesia, 12 opossums underwent biliary tract manometry. Following a stabilization period, six animals were given rHb1.1 (0.28 g/kg over 30 min), while six received bovine albumin (0.28 g/kg over 30 min). Recordings were made during the infusion and for 3 hr after the infusion. In an in vitro preparation, force transducers were used to record spontaneous contractions at two sites along the sphincter segment. After a control period, rHb1.1 (0.1 mM) or cyanomethemoglobin (0.1 mM) was added to the tissue bath and recordings continued for another 2 hr. Recombinant human hemoglobin decreased the frequency of contractions, increased resting tone, and blocked the relaxation phase of contraction in vivo. It increased the baseline amplitude, the frequency, and the peak amplitudes of contractions in vitro. Albumin or cyanomethoglobin, which are unable to bind NO, had little effect on SO motor activity. We conclude that rHb1....Continue Reading

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Citations

Mar 3, 2004·Free Radical Biology & Medicine·John S OlsonDouglas D Lemon
Jun 16, 2004·Acta Physiologica Scandinavica·P SandstromJ Svanvik
Jun 23, 1998·Artificial Cells, Blood Substitutes, and Immobilization Biotechnology·S H ZuckermanG J Rosenthal
Aug 20, 2005·Pharmacological Reviews·Noboru Toda, Arnold G Herman

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