Effects of recombinant human hemoglobin on opossum sphincter of Oddi motor function in vivo and in vitro.
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 rHb1.1 may alter SO motor function by binding endogenous NO.
Cullen
J J
JJ
Department of Surgery and Internal Medicine, University of Iowa College of Medicine, Iowa City, 52242, USA.
Conklin
J L
JL
Murray
J
J
Ledlow
A
A
Rosenthal
G
G
D000704:Analysis of Variance; D000818:Animals; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008706:Methemoglobin / Q000031:analogs & derivatives / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009893:Opossums / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000502:physiology
D016166:Free Radical Scavengers; D006454:Hemoglobins; D011994:Recombinant Proteins; C007169:cyanomethemoglobin; D012710:Serum Albumin, Bovine; D008706:Methemoglobin