EFFECTS OF RECOMBINANT HUMAN HEMOGLOBIN ON MOTOR FUNCTIONS OF THE OPOSSUM ESOPHAGUS

Chemically altered hemoglobins are being investigated as blood substit utes. They may affect numerous biological processes since free hemoglo bin binds nitric oxide (NO). Nitric oxide is a neural mediator of rela xation of the lower esophageal sphincter (LES) and esophageal peristal sis. 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. Transm embrane potential differences of circular smooth muscle from the esoph agus were recorded using glass microelectrodes. Intrinsic esophageal n erves were stimulated electrically. Esophageal manometries were perfor med with a low-compliance perfused-catheter system. The activity of th e enzyme NO synthase was determined with the citrulline assay. Recombi nant 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 p otential and shortened the latency of the off response. It increased t he velocity of esophageal peristalsis, decreased the amplitudes of the se contractions and diminished LES relaxation. Cyanomethemoglobin had little effect on nerve- or swallow-induced responses. Hemoglobin did n ot inhibit the activity of NO synthase. Recombinant human hemoglobin a ppears to alter esophageal motor function by scavenging NO.