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Das Renin-Angiotensin-System bei kardiovaskulären Erkrankungen

Renin-angiotensin system and cardiovascular diseases

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Zusammenfassung

□ Hintergrund

Die wesentlichen kardiovaskulären Erkrankungen wie die koronare Herzerkrankung, Kardiomyopathien, Klappenvitien und die arterielle Hypertonie, die alle zu einer Herzinsuffizienz führen können, sind mit einer Aktivierung des Renin-Angiotensin-Systems verbunden. Die Hemmung dieses Systems mittels Angiotensin-Konversions-Enzym-(ACE-) Hemmern oder Angiotensin-Rezeptor-Antagonisten ist in den letzten 15 Jahren zur wesentlichen Therapiesäule dieser Erkrankungen geworden.

□ Wirkungsmechanismus

Die lebensverlängernde, leistungsverbessernde und einer Progression der Herzinsuffizienz entegegenwirkende Wirkung von Eingriffen in das Renin-Angiotensin-System beruht auf mehreren Prinzipien:

  1. 1.

    Antagonisierung der als Kompensationsmechanismus bekannten Aktivierung des Renin-Angiotensin-Aldosteron-Systems mit Erhöhung des zirkulierenden Angiotensins II, Noradrenalins und Vasopressins.

  2. 2.

    Einflußnahme auf lokale Renin-Angiotensin-Systeme am Herzen und an den Gefäßen, die sowohl für die Progression der Herzinsuffizienz als auch der ihr zugrundeliegenden Erkrankungen verantwortlich sind. Die Regulationsmechanismen auf Gen- und Rezeptorebene sowie die Bedeutung weiterer Angiotensinrezeptoren bedürfen noch weiterer Klärung.

  3. 3.

    Der Verbindung zum Bradykininstoffwechsel kommt eine wichtige Bedeutung zu. Ein Teil der ACE-Hemmer-Wirkungen, wie zum Beispiel die Beeinflussung der Hypertrophie und die Vasodilatation, beruhen auf Bradykinineffekten. Hier werden zukünftige Untersuchungen mit selektiven Bradykinin-Rezeptor-Antagonisten klären, welcher Teil der ACE-Hemmer-Wirkungen auf einer Beeinflussung des Bradykininstoffwechsels beruht.

□ Schlußfolgerung

Untersuchungen mit spezifischen Rezeptorantagonisten werden weitere Klärung des komplexen Systems liefern, von dessen vollständigem Verständnis wir noch entfernt sind.

Abstract

□ Background

The renin-angiotensin system is mainly involved in several cardiovascular diseases and in the pathophysiology of heart failure. It exists as a circulating and a local system which can be differently regulated. Interventions in this system by angiotensin-converting enzyme (ACE) antagonists or angiotensin-receptor antagonists slow the progression of heart failure and result in prolongation of life expectancy and improvement of hemodynamics.

□ Mechanisms of Action

The main underlying mechanisms are:

  1. 1.

    Heart failure results in activation of the renin-angiotensin system as a compensatory mechanism with elevation of circulating angiotensin II, norepinephrine and vasopressin. Antagonists of this compensatory mechanisms acutely result in improvement of the hemodynamic situation.

  2. 2.

    Elevated circulating and local renin-angiotensin systems cause chronic structural myocardial and vascular effects. Angiotensin-converting enzyme antagonists and angiotensin-receptor blockers modulate and partly antagonize these structural changes such as myocardial hypertrophy, myocardial fibrosis and vascular proliferative responses. Gene and receptor regulation of the system are currently not fully understood and are subject of intensive research.

  3. 3.

    The renin-angiotensin system is closely related to the bradykinin system and thus indirectly to nitric oxide and endothelial function. Bradykinin has multiple other effects on the hemostatic system as a well as on the myocardium and vascular system.

□ Conclusion

These complex interactions require further evaluation. Research with specific bradykinin antagonists will give new insights into this system.

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  1. Abteilung Kardiologie und Pulmonologie der Medizinischen Universitätsklinik, Robert-Koch-Straße 40, D-37075, Göttingen, Deutschland

    Christina Unterberg & Arnd B. Buchwald

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  1. Christina Unterberg
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  2. Heinrich Kreuzer
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Unterberg, C., Kreuzer, H. & Buchwald, A.B. Das Renin-Angiotensin-System bei kardiovaskulären Erkrankungen. Med Klin 93, 416–425 (1998). https://doi.org/10.1007/BF03042638

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