Skip to main content
Log in

Captopril increases endothelin serum concentrations and preserves intestinal mucosa after mesenteric ischemia-reperfusion injury

  • Original Papers
  • Published:
Research in Experimental Medicine

Abstract

Endothelial cells modulate the tone of the underlying smooth muscle by generating endothelium-derived relaxing and constricting factors. Captopril (CPT), unlike other angiotensin-converting enzyme (ACE) inhibitors, contains a sulfhydryl (-SH) group and can act as a free radical scavenger. Iloprost (ILO) is a synthetic analogue of prostacyclin and mimics the effects of this compound. This study was designed to investigate the effect of ILO and CPT on the mechanism of endothelin (ET) release after mesenteric ischemia-reperfusion (I/R) injury in the rat. Sprague-Dawley rats were divided into five groups: sham-operated, control, ILO (25 μg/kg), CPT (10 μg/kg), and ILO+CPT. The superior, mesenteric artery was occluded for 30 min and then allowed 90 min of reperfusion, except in the sham-operated group, and the corresponding agents were given to the treated groups prior to I/R injury. After I/R injury, portal venous blood was obtained for ET assay, and ileal tissue samples were also obtained for the determination of malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) and for histopathological examination. MDA levels were significantly lower in the CPT, ILO and, ILO+CPT groups than in the control group, indicating the inhibition of lipid peroxidation in all groups. ET levels increased in the control group, and this increase was reversed with ILO. In the CPT group, ET levels were significantly increased, and the addition of ILO did not affect this increase. Significant cytopreservative effect was achieved with ILO and CPT, the latte being more prominent histopathologically. CPT exerts a significant protective effect on the intestinal mucosa after I/R injury. This protection is accomplished by increased ET levels and seems to be unrelated to its inhibitory effect on lipid peroxidation and also unrelated to the arachidonic acid cascade.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Adeagbo ASO, Malik KU (1990) Mechanism of vascular actions of prostacyclin in the rat isolated perfused mesenteric arteries. J Pharmacol Exp Ther 252: 26–34

    PubMed  CAS  Google Scholar 

  2. Aktan AÖ, Büyükgebiz O, Yeĝen C, Yalçin AS, Haklar G, Yalin R, Ercan ZS (1994) Does PGE2 act as a mediator for endothelin release?. Prostaglandins Leukot Essent Fatty Acids 50:37–41

    Article  PubMed  CAS  Google Scholar 

  3. Andersen WH, O'Donnel M, Simco BA, Welton AF (1983) An in vivo model for measuring antigen-induced SRS-A mediated bronchoconstriction and plasma SRS-A levels in the guinea pig. Br J Pharmacol 78:67–71

    Google Scholar 

  4. Arai H, Hori S, Aramori I, Ohkubo H, Nakanishi S (1990) Cloning and expression of a cDNA encoding an endothelin receptor. Nature 348: 730–732

    Article  PubMed  CAS  Google Scholar 

  5. Bulkley GB (1983) The role of oxygen free radicals in human disease, processes. Surgery 94:404–411

    Google Scholar 

  6. Carrico CJ, Meakins JL, Marshall JC et al (1986) Multiple organ failure syndrome. Arch Surg 121:196–208

    PubMed  CAS  Google Scholar 

  7. Casini A, Ferrali M, Pompella A, Maellaro E, Comporti M (1986) Lipid peroxidation and cellular damage in extrahepatic damage to tissues of bromobenzene-intoxicated mice. Am J Pathol 123:520–521

    PubMed  CAS  Google Scholar 

  8. Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN (1970) Intestinal mucosal lesions in low-flow states. A morphological, hemodynamic and metabolic reappraisal. Arch Surg 101:478–483

    PubMed  CAS  Google Scholar 

  9. De Nucci G, Thomas R, D'Orleans-Juste P, Antunes E, Walder C, Warner TD, Vane JR (1988) Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci USA 85:9797–9800

    Article  PubMed  Google Scholar 

  10. Döşlüoĝlu HH, Aktan AÖ, Yeĝen C, Okboy N, Yalçin AS, Yalin R, Ercan ZS (1993) The cytoprotective effects of verapamil and iloprost (ZK 36374) on ischemia/reperfusion injury of kidneys. Transpl Int 6: 138–142

    Article  PubMed  Google Scholar 

  11. Flaherty JT, Weisfeldt ML (1988) Reperfusion injury. Free Radic Biol Med 5: 409–419

    Article  PubMed  CAS  Google Scholar 

  12. Galli C, Parratt JR, Schrör (1987) Discussion. In: Gryglewski RJ, Stock G (eds) Prostacyclin and its stable analogue iloprost. Springer, Berlin Heidelberg New York, pp 279–286

    Google Scholar 

  13. Gardiner SM, Kemp PA, Compton AM, Bennett T (1992) Coeliac haemodynamic effects of endothelin-1, endothelin-3, proendothelin-1 [1–38] and proendothelin-3 [1–41] in conscious rats. Br J Pharmacol 106:483–488

    PubMed  CAS  Google Scholar 

  14. Gilst WH van, Wijngaarden J van, Scholtens E, Graeff PA de, Langen CDJ de, Wesseling H (1987) Captopril-induced increase in coronary flow: an SH-dependent effect on arachidonic acid metabolism?. J Cardiovasc Pharmacol 9 [Suppl 2]:S31-S36.

    Article  PubMed  Google Scholar 

  15. Goldsmith JE, Tallarida RJ (1981) Pharmacological evidence that captopril possesses an endothelium-mediated component of vasodilation: effect of sulphydryl groups on endothelium-derived relaxing factor. J Pharmacol Exp Ther 257:1136–1145

    Google Scholar 

  16. Graeff PA de, Gilst WH van, Bel K, Langen CDJ de, Kingma JH, Wesseling H (1987) Concentration-dependent protection by captopril against myocardial damage during ischemia and reperfusion in a closed chest pig model. J Cardiovasc Pharmacol 9 [Suppl 2]:S37-S42

    Article  PubMed  Google Scholar 

  17. Granger DN, Rutili G, McCord JM (1981) Superoxide radicals in feline intestinal ischemia. Gastroenterology 81:22–29

    PubMed  CAS  Google Scholar 

  18. Hock CE, Riberio LGT, Lefer AM (1985) Preservation of, ischemic myocardium by a new converting enzyme inhibitor, enalprilic acid, in acute myocardial infarction. Am Heart J 109:222–228

    Article  PubMed  CAS  Google Scholar 

  19. Ignarro LJ, Byrns RE, Buga GM, Wood KS, Chaudhuri G (1988) Pharmacological evidence that endothelium-derived relaxing factor is nitric oxide: use of pyrogallol and superoxide dismutase to study endothelium-dependent and nitric oxide-elicited vascular smooth muscle relaxation. J Pharmacol Exp Ther 244: 181–189

    PubMed  CAS  Google Scholar 

  20. Korthius RJ, Granger DN, Townsley MI et al (1985) The role of oxygen-derived free radicals in ischemia-induced increases in canine muscle vascular permeability. Circ Res 57: 599–609

    Google Scholar 

  21. Lüscher TF, Oemar BS, Boulanger CM, Hahn AWA (1993) Molecular review. Molecular and cellular biology of endothelin and its receptors. I. J Hypertens 11: 7–11

    Article  PubMed  Google Scholar 

  22. Lüscher TF, Oemar BS, Boulanger CM, Hahn AWA (1993) Molecular review. Molecular and cellular biology of endothelin, and its receptors. II. J Hypertens 11: 121–126

    Article  PubMed  Google Scholar 

  23. McCord JM (1985) Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 315: 159–163

    Google Scholar 

  24. McCord JM (1987) Oxygen-derived radicals: a link between reperfusion injury and inflammation. Fed Proc 45: 2933

    Google Scholar 

  25. Okboy N, Yeĝen C, Aktan AÖ, Döşlüoĝlu HH, Sav A, Yalin R, Ercan ZS (1992) The effect of iloprost and DNGA in ischemia reperfusion injury of rat liver. Prostaglandins Leukot Essent Fatty Acids 47:291–295

    Article  PubMed  CAS  Google Scholar 

  26. Parks DA, Granger DN (1983) Ischemia-induced microvascular changes: role of xanthine oxidase and hydroxyl radicals. Am J Physiol 245 [Gastrointest Liver Physiol 8]:G285-G289

    PubMed  CAS  Google Scholar 

  27. Parks DA, Granger DN (1986) Contributions of ischemia and reperfusion to mucosal lesion formation. Am J Physiol 250 [Gastrointest Liver Physiol 13]:G749-G753

    PubMed  CAS  Google Scholar 

  28. Parks DA, Granger DN (1986) Xanthine oxidase: biochemistry, distribution and physiology. Acta Physiol Scand 548 [Suppl]:87–100

    CAS  Google Scholar 

  29. Parks DA, Bulkley DB, Granger DN, Hamilton SR, McCord JM (1982) Ischemic injury to the cat small intestine: role of free radicals. Gastroenterology 82:9–15

    PubMed  CAS  Google Scholar 

  30. Sakamato A, Yanagisawa M, Sawamura T, Enoki T, Ohtani T, Sakurai, T, Nakao K, Toyoka T, Masaki T (1993) Distinct subdomains of human endothelin receptors determine their selectivity to endothelin A-selective antagonist and endothelin, B-selective agonists. J Biol Chem 268:8547–8553

    Google Scholar 

  31. Sakurai T, Yanagisawa M, Tekuwa Y, Miyazaki H, Kimura S, Goto K, Masaki T (1990) Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature 348:732–735

    Article  PubMed  CAS  Google Scholar 

  32. Samnoun MN, Piper PJ (1984) A combined use of isolated strips of guinea pig lung parenchyma and ileum as a sensitive bioassay for leukotriene C4. Prostaglandins 27:711–714

    Article  Google Scholar 

  33. Schroeder G, Beckmann R, Schillinger E (1987) Studies on vasorelax effects and mechanisms of iloprost and isolated preparations. In: Gryglevski RJ, Stock G (eds) Prostacyclin and its stable analogue iloprost. Springer, Berlin Heidelberg New York, pp 129–137

    Google Scholar 

  34. Shepherd JT, Katusic ZS (1991) Endothelium-derived vasoactive factors I.. Hypertension 18 [Suppl III]:76–85

    Google Scholar 

  35. Swartz SL, Williams GH, Hollenberg NK, Levine L, Dluhy RG, Moore TC (1980) Captopril-induced changes in prostaglandin production: relationship to vascular responses in normal man. J Clin Invest 65:1257–1264

    PubMed  CAS  Google Scholar 

  36. Türker RK, Demirel E, Ercan ZS (1988) Iloprost preserves kidney function against anoxia. Prostaglandins Leukot Essent Fatty Acids 31: 45–52

    Article  PubMed  Google Scholar 

  37. Vanhoutte PM (1988) The endothelium—modulator of vascular smooth-muscle tone. N Engl J Med 25: 512–513

    Article  Google Scholar 

  38. Vanhoutte PM, Katusic ZS (1988) Endothelium-derived contracting factor: endothelium and/or superoxide anion?. Trends Pharmacol Sci 332:411–415

    Google Scholar 

  39. Warner TD, De Nucci G, Vane JR (1989) Rat endothelin is a vasodilator in the isolated perfused mesentery of the rat. Eur J Pharmacol 159:325–326

    Article  PubMed  CAS  Google Scholar 

  40. Westlin W, Mullane K (1988) Does captopril attenuate reperfusion-induced myocardial dysfunction by scavenging free radicals?. Circulation 77 [Suppl 6]:130–139

    Google Scholar 

  41. Yanagisava M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415

    Article  Google Scholar 

  42. Yeĝen C, Aktan AÖ, Büyükgebiz O, Haklar G, Yalçin AS, Yalin R, Ercan ZS (1994) The effect of verapamil and iloprost (ZK 36374) on endothelin release after mesenteric ischemia reperfusion injury. Eur Surg Res 26: 69–75

    PubMed  Google Scholar 

  43. Zusman RM (1984) Renin-and nonrenin-mediated antihypertensive action of converting enzyme inhibition. Kidney Int 25:96–983

    Google Scholar 

  44. Zweier JL, Rayburn BK, Flaherty JT et al (1987) Recombinant superoxide dismutase reduces oxygen free radical concentrations in reperfused myocardium. J Clin Invest 80: 1728–1734

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Büyükgebiz, O., Aktan, A.Ö., Yeĝen, C. et al. Captopril increases endothelin serum concentrations and preserves intestinal mucosa after mesenteric ischemia-reperfusion injury. Res. Exp. Med. 194, 339–348 (1994). https://doi.org/10.1007/BF02576396

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02576396

Key words

Navigation