Sucralfate pp 151-162 | Cite as

Vascular Factors

Mucosal Vasoprotection and Angiogenesis
  • Zsuzsa Sandor
  • Sandor Szabo


Vascular factors refer to acute endothelial damage and protection, regulation of blood flow, and generation of new blood vessels (angiogenesis). The investigation of vascular factors is a relatively new subject in ulcer research. 15 Historically, most of the experimental work on the stomach was related to the structure and function of epithelial cells (e.g., gastric secretion) (Table 1). This was in part the result of conceptual focus on epithelial cells and availability of methods. Subsequently, blood flow was investigated per se in relation to gastric secretion, mucosal injury, and ulcer localization in the stomach and duodenum. If ischemia was considered, it was ascribed to external or internal (e.g., thrombosis) narrowing and not to active involvement of endothelial cells (e.g., in regulating vascular permeability).


Vascular Injury Granulation Tissue Ulcer Healing Mucosal Blood Flow Gastric Mucosal Injury 
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  1. 1.
    Burch RM, McMillan BA: Sucralfate induces proliferation of dermal fibroblasts and keratinocytes in culture and granulation tissue formation in full-thickness skin wounds. Agents Actions 34:229–231, 1991. Sucralfate has direct effects on wound healing in the skin; it increases the thickness of granulation tissue and induces the proliferation of keratinocytes and fibroblasts in culture.PubMedCrossRefGoogle Scholar
  2. 2.
    Chen BW, Hui WM, Lam SK, et al: Effect of sucralfate on gastric mucosal blood flow in rats. Gut 30:1544–1551, 1989. Sucralfate increases gastric mucosal blood flow and lessens the fall in blood flow after ethanol treatment in a dose-dependent manner in rats. This action may contribute to the gastroprotective effect of the drug.PubMedCrossRefGoogle Scholar
  3. 3.
    Cotran RC, Kumar V, Robbins SL: Robbins Pathologic Basis of Disease, ed 4. Philadelphia, WB Saunders, 1989. One of the best textbooks of pathology.Google Scholar
  4. 4.
    Folkman J, Szabo S, Shing, Y: Sucralfate affinity for fibroblast growth factor. J Cell Biol 111:223A, 1990. The first demonstration of bFGF binding to sucralfate in vitro, in comparison with heparin.Google Scholar
  5. 5.
    Folkman J, Szabo S, Stovroff M, et al: Duodenal ulcer: Discovery of a new mechanism and development of angiogenic therapy that accelerates healing. Ann Surg 214:414–426, 1991. Extensive in vitro and in vivo studies on sucralfate binding of bFGF, and the demonstration of elevated levels of bFGF in chronic duodenal ulcers treated with sucralfate in rats.PubMedCrossRefGoogle Scholar
  6. 6.
    Galli SJ, Bose R, Szabo S: Mast cell dependent augmentation of ethanol-induced acute gastric damage in mice. Dig Dis Sci 30:375, 1985. Demonstration of role of mast cells and vascular factors in acute mucosal injury using mouse strains deficient in mast cells.Google Scholar
  7. 7.
    Guth PH, Poulsen G, Nagata H: Histologic and microcirculatory changes in alcohol-induced gastric lesions in the rat: Effect of prostaglandin cytoprotection. Gastroenterology 87:1083–1090, 1984. This paper documents the stages of congestion in histologic sections of the rat stomach soon after administration of ethanol.PubMedGoogle Scholar
  8. 8.
    Hui WM, Chen BW, Cho CH, et al: Role of gastric blood flow in cytoprotection. Digestion 48:113–120, 1991. Comparative study on the effects of misoprostol, omeprazole, cimetidine, and sucralfate on gastric mucosal blood flow. Sucralfate, misoprostol, and omeprazole but not cimetidine increased gastric mucosal blood flow in a dose-dependent manner. The blood flow was significantly greater after sucralfate in comparison with other drugs.PubMedCrossRefGoogle Scholar
  9. 9.
    Morales RE, Johnson BR, Szabo S: Endothelin induces vascular and mucosal lesions, enhances the injury by HCl/ethanol, and the antibody exerts gastroprotection. FASEB J 6:2354–2360, 1992. Intraarterial infusion of endothelin caused vascular injury as revealed by monastral blue deposition and markedly aggravated the chemically induced gastric mucosal injury.PubMedGoogle Scholar
  10. 10.
    Pihan G, Majzoubi D, Haudenschild C, et al: Early microcirculatory stasis in acute gastric mucosal injury in the rat and prevention by 16,16-dimethyl prostaglandin E2 or sodium thiosulfate. Gastroenterology 91:1415–1426, 1986. This paper describes the functional detection of congestion by laser-Doppler technique. The ethanol-induced decrease in blood flow was counteracted both by prostaglandins and by sulfhydryl derivatives despite the fact that these two protective agents, given alone, have differential effects on mucosal blood flow.PubMedGoogle Scholar
  11. 11.
    Pihan G, Szabo S, Trier JS: The role of microvasculature in acute gastric mucosal damage and protection, in Szabo S, Pfeiffer CJ (eds): Ulcer Disease: New Aspects of Pathogenesis and Pharmacology. Boca Raton, Fla, CRC Press, 1989, pp 135–145. A general review on the functional and structural, including electron-microscopic alterations in blood vessels and supply during acute gastric mucosal injury and protection.Google Scholar
  12. 12.
    Robert A: On the mechanism of cytoprotection, in Szabo S, Pfeiffer CJ (eds): Ulcer Disease: New Aspects of Pathogenesis and Pharmacology. Boca Raton, Fla, CRC Press, 1989, pp 417–421. A historic review by the discoverer of “cytoprotection” on the mechanisms of acute gastric mucosal protection, concluding that one of the key events is the maintenance of mucosal blood flow by protective agents.Google Scholar
  13. 13.
    Sandor Z, Szabo S: Steroids and ulcers, in Braga PC, Guslandi M (eds): Drug-Induced Injury to the Digestive System. Berlin, Springer-Verlag, 1993 (in press). A modern review on the effect of all types of steroids on the gut, synthesizing both human and animal data. Special emphasis is placed on glucocorticoids and the recently discovered angiosteroids, i.e., angiogenic and angiostatic naturally occurring and synthetic steroids.Google Scholar
  14. 14.
    Szabo S: Critical and timely review of the concept of gastric cytoprotection. Acta Physiol Hung 73:115–127, 1989. A critical and historical review that covers not only prostaglandins but other gastroprotective agents as well, and emphasizes the vascular factors as key elements in the mechanisms of mucosal protection.PubMedGoogle Scholar
  15. 15.
    Szabo S: Pharmacological modulation of cellular, vascular and motility factors, in Garner A, Whittle BJR (eds): Advances in Drug Therapy of Gastrointestinal Ulceration. New York, John Wiley &0026; Sons, Ltd, 1989. An in-depth and analytic review of mucosal protection through separate discussion of cellular, vascular, and motility factors.Google Scholar
  16. 16.
    Szabo S: The mode of action of sucralfate: The 1×1×1 mechanism of action. Scand J Gastroenterol 26(suppl 185):7–12, 1991. This is a detailed and critical review of the mechanisms of actions of sucralfate, emphasizing that not all actions of the drug are equally important for acute gastroprotection and healing of chronic ulcers. It is proposed that prevention of vascular injury, maintenance of mucosal blood flow allowing rapid epithelial restitution are key mechanisms for acute gastroprotection, in both acute and chronic action of sucralfate, while local binding and concentration of growth factors such as bFGF and EGF are the elements of stimulated chronic ulcer healing by sucralfate.CrossRefGoogle Scholar
  17. 17.
    Szabo S, Brown A: Prevention of ethanol-induced vascular injury and gastric mucosal lesions by sucralfate and its components: Possible role of endogenous sulfhydryls. Proc Soc Exp Biol Med 185:493–497, 1987. This rat study demonstrated that the gastroprotective action of sucralfate is mediated by a sulfhydryl-sensitive process, which is counteracted by the sulfhydryl alkylator N-ethylmaleimide. It was also shown that sulfate and sucrose octasulfate are the most potent gastroprotective components of sucralfate, and that the early ethanol-induced vascular injury is preventable not only by sucralfate but by its components as well, especially sulfates.PubMedGoogle Scholar
  18. 18.
    Szabo S, Folkman J, Vattay P, et al: Duodenal ulcerogens: Effect of FGF on cysteamine-induced duodenal ulcer, in Halter F, Garner A, Tytgat GNJ (eds): Mechanisms of Peptic Ulcer Healing. London, Kluwer Academic Pub, 1991, pp 139–150. Review of animal models of duodenal ulceration, and the first overview of the very potent ulcer healing properties of bFGF in rats with experimental duodenal ulcer.Google Scholar
  19. 19.
    Szabo S, Hollander D: Pathways of gastrointestinal protection and repair: Mechanism of action of sucralfate. Am J Med 86(suppl 6A):23–31, 1989. Detailed overview of the processes of gastrointestinal protection and repair with special emphasis on the mechanism of sucralfate in acute gastroprotection and chronic ulcer healing.PubMedCrossRefGoogle Scholar
  20. 20.
    Szabo S, Trier JS, Brown A, et al: Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology 88:228–236, 1985. This is the first paper in a peer-reviewed journal describing the rapidly developing vascular tracers, monastral blue and colloidal carbon after administration of ethanol in rat. The lesions were prevented by prostaglandins and sulfhydryl derivatives.PubMedGoogle Scholar
  21. 21.
    Szabo S, Vattay P, Scarbrough E, et al: Role of vascular factors, including angiogenesis, in the mechanism of action of sucralfate. Am J Med 91(suppl 2A):158–160, 1991. Demonstration of enhanced angiogenesis and granulation tissue production in s.c.-implanted sponges in rats: sucralfate was more potent than the water-soluble sucrose octasulfate.CrossRefGoogle Scholar
  22. 22.
    Tarnawski A, Hollander D, Stachura J, et al: Prostaglandin protection of the gastric mucosa against alcohol injury—A dynamic time-related process. Role of the mucosal proliferative zone. Gastroenterology 88:334–352, 1985. This paper compares the protective effect of prostaglandins and emphasizes the importance of preserving the proliferative zone for rapid restitution.PubMedGoogle Scholar

Copyright information

© Plenum Press 1995

Authors and Affiliations

  • Zsuzsa Sandor
    • 1
  • Sandor Szabo
    • 1
  1. 1.Chemical Pathology Research Division, Department of PathologyBrigham & Women’s Hospital, and Harvard Medical SchoolBoston

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