Effects of recombinant human hemoglobin on motor functions of the opossum esophagus

J. L. Conklin, Joseph A Murray, A. Ledlow, E. Clark, B. Hayek, H. Picken, G. Rosenthal

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Chemically altered hemoglobins are being investigated as blood substitutes. They may affect numerous biological processes since free hemoglobin binds nitric oxide (NO). Nitric oxide is a neural mediator of relaxation of the lower esophageal sphincter (LES) and esophageal peristalsis. We hypothesize that recombinant human hemoglobin (rHb1.1) alters esophageal motor function by scavenging NO. Contraction of transverse muscle strips from the opossum esophagus and LES was monitored. Transmembrane potential differences of circular smooth muscle from the esophagus were recorded using glass microelectrodes. Intrinsic esophageal nerves were stimulated electrically. Esophageal manometries were performed with a low- compliance perfused-catheter system. The activity of the enzyme NO synthase was determined with the citrulline assay. Recombinant hemoglobin diminished nerve-induced relaxation of LES muscle but did not alter LES tone. Circular esophageal muscle responded to nerve stimulation with an inhibitory junction potential and a mechanical off response. Recombinant hemoglobin diminished the inhibitory junction potential and shortened the latency of the off response. It increased the velocity of esophageal peristalsis, decreased the amplitudes of these contractions and diminished LES relaxation. Cyanomet- hemoglobin had little effect on nerve- or swallow-induced responses. Hemoglobin did not inhibit the activity of NO synthase. Recombinant human hemoglobin appears to alter esophageal motor function by scavenging NO.

Original languageEnglish (US)
Pages (from-to)762-767
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume273
Issue number2
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology

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    Conklin, J. L., Murray, J. A., Ledlow, A., Clark, E., Hayek, B., Picken, H., & Rosenthal, G. (1995). Effects of recombinant human hemoglobin on motor functions of the opossum esophagus. Journal of Pharmacology and Experimental Therapeutics, 273(2), 762-767.