Abstract
Chemically altered hemoglobin-based oxygen carriers have been developed as prototype blood substitutes. Such molecules may affect numerous biological processes, since free hemoglobin scavenges nitric oxide (NO). Diaspirin cross-linked hemoglobin (DCLHb) is a chemically cross-linked molecule, which has a pressor effect on blood pressure, mainly mediated by NO scavenging. However, the effects of DCLHb on the gastrointestinal and biliary motility have not been reported. This study was conducted to investigate the effects of DCLHb on the duodenal and biliary motility and determine if the underlying mechanism involves a NO pathway. Blood pressure, duodenal, sphincter of Oddi and gallbladder motility and trans-sphincteric flow were recorded in anesthetized Australian Brush-tailed possums. The effects of intravenously administered DCLHb (10% solution) or oncotically matched human serum albumin (HSA) solution on these parameters were investigated. To determine the involvement of a NO-mediated pathway in these effects, animals were pretreated withNω-nitro-l-arginine methyl ester (l-NAME) before DCLHb or HSA was given. DCLHb increased blood pressure and duodenal contraction frequency and slowed trans-sphincteric flow compared with the HSA control. The effects of DCLHb on blood pressure and trans-sphincteric flow were immediate and transient, whereas the effect on duodenal contraction frequency was delayed and long-lived. Pretreatment with l-NAME alone increased blood pressure and duodenal contraction frequency and slowed trans-sphincteric flow. DCLHb-induced changes were not evident in the presence of l-NAME. These findings suggest that DCLHb affects duodenal and trans-sphincteric flow predominantly by NO scavenging.
Footnotes
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Send reprint requests to: Dr. Gino T. P. Saccone, Department of General and Digestive Surgery, Flinders Medical Center, Bedford Park, SA 5042, Australia. E-mail: gino.saccone{at}flinders.edu.au
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This work was supported by Baxter Healthcare Corp. (grant-in-aid) and National Health and Medical Research Council of Australia.
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Parts of this work were presented at the 99th Annual Meeting of the American Gastroenterological Association, May 16–22, 1998, New Orleans, LA; Brisbane '98, September 27 through October 1, 1998, Brisbane, QLD, Australia; Australian Gastrointestinal Week 1998, Canberra, ACT, Australia; The Japanese Surgical Society, March 1999 and March 2000. Abstracts were published previously [Gastroenterology115:A771 (1998);Proc Australian Physiol Pharmacol Soc29:193P (1998); J Gastroenterol Hepatol13:A184 (1998);J Jpn Surg Soc100:225 (1999); J Jpn Surg Soc101:426 (2000), respectively].
- Abbreviations:
- HBOC
- hemoglobin based oxygen carriers
- DCLHb
- diaspirin cross-linked hemoglobin
- l-NAME
- Nω-nitro-l-arginine methyl ester
- NO
- nitric oxide
- SO
- sphincter of Oddi
- HSA
- human serum albumin
- Received July 18, 2000.
- Accepted November 7, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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