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, Volume 54, Supplement 5, pp 23–30 | Cite as

The Role of Kinins in the Antihypertensive and Cardioprotective Effects of ACE Inhibitors

  • Gerd Bönner
Article

Summary

Kinins are highly potent vasoactive peptides. They reduce blood pressure by vasodilation and are cardio- and vasoprotective. ACE inhibitors potentiate the actions of endogenous kinins by about 50-fold. Kinins are involved in the blood pressure-lowering effects of ACE inhibitors in all forms of hypertension associated with stimulation of the renin-angiotensin system. In addition, kinins play an important role in the metabolic, and cardio- and vasoprotective effects of ACE inhibitors.

Keywords

Captopril Bradykinin Ramipril Systemic Blood Pressure Brown Norway 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Bönner G, Preis S, Schunk U, et al. In: Fritz H, Schmidt I, Dietze G, editors. The kallikrein-kinin system in health and disease. Braunschweig: Limbach Verlag, 1989: 79–96Google Scholar
  2. 2.
    Wiemer G, Schölkens BA, Becker RHA, et al. Ramiprilat enhances endothelial autacoid formation by inhibiting breakdown of endothelium-derived bradykinin. Hypertension 1991; 18(4): 558–63PubMedCrossRefGoogle Scholar
  3. 3.
    Bönner G, Schunk U, Preis S, et al. Effect of bradykinin on systemic and pulmonary hemodynamics in the human. Klin Wochenschr 1989; 67(21): 1085–95PubMedCrossRefGoogle Scholar
  4. 4.
    Bönner G, Preis S, Schunk U, et al. Hemodynamic effects of bradykinin on systemic and pulmonary circulation in healthy and hypertensive humans. J Cardiovasc Pharmacol 1990; 15 Suppl. 6: S46–56PubMedGoogle Scholar
  5. 5.
    Bönner G, Preis S, Schunk U, et al. Effect of bradykinin on arteries and veins in systemic and pulmonary circulation. J Cardiovasc Pharmacol 1992; 20 Suppl. 9: S21–7PubMedCrossRefGoogle Scholar
  6. 6.
    Collier J, Vallance P. Role of nitric oxide in the vasodilator response to bradykinin in human peripheral veins and arteries in situ [abstract]. In: Kinin 91 Abstract book: International Conference Kinin 91. Munich: 1991: 47Google Scholar
  7. 7.
    Bönner G, Rütten H, Chrosch R, et al. Efficacy of HOE 140, a B2-kinin receptor antagonist, measured by bradykinin injections — a dose finding study. Am J Hypertens 1994; 7: 137AGoogle Scholar
  8. 8.
    Rütten H, Chrosch R, Müller R, et al. Hemodynamic effects of the kinin B2-receptor antagonist HOE 140 on systemic and pulmonary circulation in healthy men. Can J Physiol Pharmacol 1994; 72 Suppl. 2: 23Google Scholar
  9. 9.
    Cockcroft JR, Chowienczyk PJ, Brett SA, et al. Inhibition of bradykinin-induced vasodilation in the human forearm vasculature by icatibant, a B2-receptor antagonist. Br J Clin Pharmacol 1994; 38: 317–22PubMedCrossRefGoogle Scholar
  10. 10.
    Bönner G, Rütten H, Chrosch R, et al. Changes in systemic and pulmonary hemodynamics by kinin B2-receptor antagonist HOE 140 in healthy man [abstract book]. 18th Meeting of the German Society of Hypertension. M:unster: 1994: 17Google Scholar
  11. 11.
    Dietze G, Wicklmayr M, Mayer L. In: Haberland GL, Rohen JW, Suzuki T, editors. Kininogenases. Kallikrein. Stuttgart: Schattauer Verlag, 1977; 291–8Google Scholar
  12. 12.
    Linz W, Martorana PA, Schölkens BA. Local inhibition of bradykinin degradation in ischemic hearts. J Cardiovasc Pharmacol 1990; 15 Suppl. 6: S99–109PubMedGoogle Scholar
  13. 13.
    Martorana PA, Kettenbach B, Breipohl G, et al. Reduction of infarct size by local angiotensin-converting enzyme inhibition is abolished by a bradykinin antagonist. Eur J Pharmacol 1990; 182(2): 395–6PubMedCrossRefGoogle Scholar
  14. 14.
    Bönner G, Barbulescu I, Toussaint C. Protektive Wirkung von Bradykinin auf die Reperfusionsarrhythmie am isoliert perfundierten Rattenherz. Herz/Kreislauf 1989; 21 Suppl. 11: 39–42Google Scholar
  15. 15.
    Bönner G, Barbulescu I, Toussaint C. Zofenopril verhindert die Reperfusionsarrhythmie nach regionaler Ischämie am isoliert, fluss-konstant perfundierten Rattenherz. Hochdruck 1989; 9: 41Google Scholar
  16. 16.
    Haberland GL. The role of kininogenases, kinin formation and kininogenase inhibition in post-traumatic shock and related conditions. Klin Wochenschr 1978; 56: 325–31PubMedCrossRefGoogle Scholar
  17. 17.
    Scicli AG, Orstavik TB, Rabito S, et al. Blood kinins after sympathetic nerve Stimulation of the rat submandibular gland. Hypertension 1983; 5 (2 Pt 2): 1101–6Google Scholar
  18. 18.
    Orstavik TB, Carretero OA, Johansen L, et al. Role of kallikrein in the hypotensive effect of captopril after sympathetic Stimulation of the rat submandibular gland. Circ Res 1982; 51: 385–90PubMedCrossRefGoogle Scholar
  19. 19.
    Rabito SF, Orstavik TB, Scicli AG, et al. Role of the autonomic nervous system in the release of rat submandibular gland kallikrein into the circulation. Circ Res 1983; 52: 635–41PubMedCrossRefGoogle Scholar
  20. 20.
    Hornig B, Köhler C, Drexler H. Role of bradykinin in mediating vascular effects of angiotensin-converting enzyme inhibitors in humans. Circulation 1997; 95: 1115–8PubMedCrossRefGoogle Scholar
  21. 21.
    Bönner G. Kinin-related effects of ACE inhibition. Clin Physiol Biochem 1990; 8 Suppl. 1: 6–15PubMedGoogle Scholar
  22. 22.
    Carretero OA, Miyazaki S, Scicli AG. Role of kinins in the acute antihypertensive effect of the converting enzyme inhibitor captopril. Hypertension 1981; 3: 18–22PubMedCrossRefGoogle Scholar
  23. 23.
    Rasmussen S, Nielsen F, Ibsen H, et al. Blood bradykinin concentration remains unchanged during captopril treatment. Agents Actions 1982; 9 Suppl.: 592–7Google Scholar
  24. 24.
    Bönner G. Haben die Kinine eine Bedeutung für die antihypertensive Wirkung der ACE-Hemmer? Z Kardiol 1988; 77 Suppl.: 23–7PubMedGoogle Scholar
  25. 25.
    Masuda A, Shimamoto K, Ando T, et al. The mechanism of the hypotensive effect of ramipril (HOE 498) in patients with essential hypertension. In: Iimura O, Margolius HS, editors. Renal function, hypertension and the kallikrein-kinin system. Tokyo: Hokusen-sha Publishing CO, 1988: 189–94Google Scholar
  26. 26.
    Rett K, Lotz N, Wicklmayr M, et al. Verbesserte Insulinwirkung durch ACE-Hemmung beim Typ II-Diabetiker. Dtsch Med Wochenschr 1988; 113: 243–9PubMedCrossRefGoogle Scholar
  27. 27.
    Shimamoto K, Iimura O. Measurements of circulating kinins, their changes by inhibition of kininase II and their possible blood pressure lowering effect. Agents Actions 1987; 22 Suppl.: 297–307Google Scholar
  28. 28.
    Campbell DJ, Kladis A, Duncan AM. Differential effects of converting enzyme inhibition on angiotensin and bradykinin peptides in rat kidney and heart. Ricera Scientifica ed Educatione Permanente (Milan) 1993; Suppl. 95: 102Google Scholar
  29. 29.
    Bönner G, Iwersen D, Shimamoto K. The analytical value for kinin concentration in blood depends on the antiserum used in the bradykinin radioimmunoassay. J Clin Chem Clin Biochem 1987; 25: 39–43PubMedGoogle Scholar
  30. 30.
    Benetos A, Gavras I, Gavras H. Hypertensive effect of a bradykinin antagonist in normotensive rats. Hypertension 1986; 8(11): 1089–92PubMedCrossRefGoogle Scholar
  31. 31.
    Benetos A, Gavras H, Stewart JM, et al. The antihypertensive contribution of bradykinin as assessed by a specific bradykinin antagonist. Agents Actions 1987; 22 Suppl.: 355–64CrossRefGoogle Scholar
  32. 32.
    Carbonell LF, Carretero OA, Maddedu P, et al. Effects of a kinin antagonist on mean blood pressure. Hypertension 1988; 11 Suppl.: 84–8CrossRefGoogle Scholar
  33. 33.
    Carbonell LF, Carretero OA, Stewart JM, et al. Effect of a kinin antagonist on the acute antihypertensive activity of enalaprilat in severe hypertension. Hypertension 1988; 11(3): 239–43PubMedCrossRefGoogle Scholar
  34. 34.
    Danckwardt L, Shimizu I, Bönner G, et al. Converting enzyme inhibition in kinin-deficient Brown Norway rats. Hypertension 1990; 16(4): 429–35PubMedCrossRefGoogle Scholar
  35. 35.
    Bönner G, Baumann J, Chrosch R, et al. ACE-Hemmung und Zuckerstoffwechsel. Hochdruck 1991; 11: 43–6Google Scholar
  36. 36.
    Bönner G. Bedeutung der Kinine für die ACE-Hemmer. Cassella Riedel Arch 1992; 75(3): 17–20Google Scholar
  37. 37.
    Bönner G, Döring R, Baumanns J, et al. ACE-Hemmer wirken über endogene Kinine auf den Zuckerstoffwechsel. Hochdruck 1992; 12: 37–8Google Scholar
  38. 38.
    Roesen P, Eckel J, Reinauer H. Influence of bradykinin on glucose uptake and metabolism studied in isolated cardiac myocytes and isolated perfused rat hearts. Hoppe Seylers Zeitschr Physiol Chem 1983; 364: 1431–8CrossRefGoogle Scholar
  39. 39.
    van Gilst WH, de Graeff PA, Wesseling H, et al. Reduction of reperfusion arrhythmias in the ischemic isolated rat heart by angiotensin converting enzyme inhibitors: a comparison of captopril, enalapril, and HOE 498. J Cardiovasc Pharmacol 1986; 8: 722–8PubMedGoogle Scholar
  40. 40.
    Linz W, Schölkens BA. In: Bönner G, Schölkens BA, Scicli AG, editors. The role of bradykinin in the cardiovascular action of the converting enzyme inhibitor ramipril. Chichester: Media Medica, 1992: 85–90Google Scholar
  41. 41.
    Farhy RD, Ho KL, Carretero OA, et al. Kinins mediate the antiproliferative effect of ramipril in rat carotid artery. Biochem Biophys Res Comm 1992; 182(1): 283–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  • Gerd Bönner
    • 1
  1. 1.Clinic Lazariterhof at the Centre for Medical RehabilitationBad KrozingenGermany

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