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Differential Effect of Nitric Oxide Inhibition as a Function of Preservation Period in Pancreas Transplantation

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Abstract

The role of nitric oxide, produced duringreperfusion as a function of preservation time, in thedevelopment of the inflammatory process in pancreastransplantation has been explored. For this purpose, the effect of nitric oxide synthase inhibition,as well as 6-keto-prostaglandin F,leukotriene B4, and lipoperoxidation levelswere evaluated in an experimental model of rat pancreastransplantation after different periods of cold preservation.The results show posttransplantation increases in6-keto-prostaglandin F, leukotrieneB4, and lipoperoxidation levels in pancreatictissue and in plasma lipase. When ischemia was induced for 30 min, nitricoxide synthase inhibition prevented these increases, andL-arginine was able to reverse this effect. By contrast,nitric oxide synthase inhibition has no effect when ischemia was prolonged for 12 hr. Insummary, this study suggests that, during reperfusion,nitric oxide modulates 6-keto-prostaglandinF synthesis, lipoperoxidation levels,and the development of pancreatic injury but only whenthe ischemic period is quite short.

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REFERENCES

  1. Ialenti A, Ianaro A, Moncada S, Di Rosa M: Modulation of acute inflammation by endogenous nitric oxide. Eur J Pharmacol 211:177-182, 1992

    Google Scholar 

  2. Ialenti A, Moncada S, Di Rosa M: Modulation of adjuvant arthritis by endogenous nitric oxide. Br J Pharmacol 110:701-706, 1993

    Google Scholar 

  3. Boughton-Smith NK, Evans SM, Whittle BJR, Moncada S: Induction of nitric oxide synthase in rat intestine and its association with tissue injury. Agents Actions 38:C125-C126, 1993

    Google Scholar 

  4. Moncada S: The L-arginine:nitric oxide pathway. Acta Physiol Scand 19:147-169, 1992

    Google Scholar 

  5. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA: Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620-1624, 1990

    Google Scholar 

  6. Kubes P: Ischemia-reperfusion in feline small intestine: A role for nitric oxide. Am J Physiol 264:G143-G149, 1993

    Google Scholar 

  7. Gaboury J, Woodman RC, Granger N, Reinhardt P, Kubes P: Nitric oxide prevents leukocyte adherence: Role of superoxide. Am J Physiol 34:H862-H867, 1993

    Google Scholar 

  8. Moncada S, Higgs A: Mechanisms of disease. The L-arginine-nitric oxide pathway. N Engl J Med 30:2001-2012, 1993

    Google Scholar 

  9. Buckberg GD, Matheis G, Sherman MP, Haybron DM, Ignarro LJ: Myocardial reoxygenation injury after ischemia is mediated by the L-arginine:nitric oxide pathway. In the Biology of Nitric Oxide, Vol I. S Moncada, MA Marletta, JB Hibbs Jr, EA Higgs (eds). London, Portland Press, 1992, pp 52-54

    Google Scholar 

  10. Matheis G, Sherman MP, Buckberg GD, Haybron DM, Young HH, Ignarro LJ: Role of L-arginine-nitric oxide pathway in myocardial reoxygenation injury. Am J Physiol 262:H616-H620, 1992

    Google Scholar 

  11. Aoki N, Johnson III, Lefer AM: Beneficial effects of two forms of NO administration in feline splanchnic artery occlusion shock. Am J Physiol 258:G275-G281, 1990

    Google Scholar 

  12. Hutcheson IR, Whittle BJR, Boughton-Smith NK: Role of nitric oxide in maintaining vascular integrity in endotoxin-induced acute intestinal damage in the rat. Br J Pharmacol 101:815-820, 1990

    Google Scholar 

  13. Clavien PA, Robert P, Harvey C, Strasberg SM: Preservation and reperfusion injuries in liver allografts. Transplantation 53:957-978, 1992

    Google Scholar 

  14. Winchell RJ, Halasz NA: Lack of effect of oxygen-radical scavenging systems in the preserved reperfused rabbit kidney. Transplantation 48:393-396, 1989

    Google Scholar 

  15. Hotter G, Leon OS, Roselló-Catafau J, López-Boado MA, Puig-Parellada P, Henriques RD, Fernández-Cruz L, Gelpí E: Tissular prostanoid release, phospholipase A2 activity, and lipid peroxidation in pancreas transplantation. Transplantation 51:987-990, 1991

    Google Scholar 

  16. Hotter G, Closa D, Pi F, Prats N, Fernandez-Cruz L, Bulbena O, Gelpi E, Rosello-Catafau J: Nitric oxide and arachidonate metabolism in ischemia-reperfusion associated with pancreas transplantation. Transplantation 59:417-421, 1995

    Google Scholar 

  17. Lee S, Tung KS, Koopmans H, Chandler JG, Orloff MJ: Pancreaticoduodenal transplantation in the rat. Transplantation 13:421-428, 1972

    Google Scholar 

  18. Ramis I, Roselló-Catafau J, Artigot M, Bulbena O, Picado C, Gelpí E: Simultaneous reversed-phase extraction of lipoxygenase and cyclooxygenase metabolites of arachidonic acid in nasal secretions: methodological aspects. J Chromatogr Biomed Appl 532:217-221, 1990

    Google Scholar 

  19. Desiderio DM, Cunninham MD, Trimble JA: High performance liquid chromatography separation and quantification of picomole amounts of prostaglandins utilizing a novel triethylamine formate buffer. J Liquid Chromatogr 4:1261-1268, 1981

    Google Scholar 

  20. Eskra JM, Pereira MJ, Ernest J: Solid phase extraction and high performance liquid chromatography analysis of lipoxygenase pathway products. Anal Biochem 154:332-338, 1986

    Google Scholar 

  21. Hotter G, Closa D, Prados M, Fernández-Cruz L, Prats N, Gelpí E, Roselló-Catafau J: Intestinal Preconditioning is mediated by a transient increase in nitric oxide. Biochem Biophys Res Commun 222:27-32, 1996

    Google Scholar 

  22. Koyama I, Bulkley GB, Williams GM, Im HJ: The role of oxygen free radicals in mediating the reperfusion injury of cold-preserved ischemic kidneys. Transplantation 40:590-595, 1985

    Google Scholar 

  23. McCord JM: Oxygen derived free radicals in post-ischemic tissue injury. N Engl J Med 312:159-165, 1985

    Google Scholar 

  24. Lefer A, Lefer D: Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock. Annu Rev Pharmacol Toxicol 33:71-90, 1993

    Google Scholar 

  25. Mangino MJ, Anderson CHB, Murphy MK, Brunt E, Turk J: Mucosal arachidonate metabolism and intestinal ischemia-reperfusion injury. Am J Physiol 257:G299-G323, 1989

    Google Scholar 

  26. Hotter G, Closa D, Pi F, Fernández-Cruz L, Gelpí E, Roselló-Catafau J: Nitric oxide enhances 12-HETE versus LTB4 generation in pancreas transplantation. Inflammation 20:23-31, 1996

    Google Scholar 

  27. López-Boado MA, Colomer J, Targarona EM, Pi F, Sáenz A, Martrat A, Klaustermeier J, Pavía A, Hotter G, Gelpí E, Fernández-Cruz L: Free radical ablation prevents ischemic injury after long periods of cold storage in rat pancreas transplantation. Transplant Proc 2:2241-2242, 1990

    Google Scholar 

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Fernandez-Cruz, L., Badosa, F., Gelpi, E. et al. Differential Effect of Nitric Oxide Inhibition as a Function of Preservation Period in Pancreas Transplantation. Dig Dis Sci 42, 962–971 (1997). https://doi.org/10.1023/A:1018824700470

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