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Pathophysiologie der Herzinsuffizienz und das Renin-Angiotensin-System

  • J. Holtz

Zusammenfassung

Ursprünglich ist die Hemmung des Renin-Angiotensin-Systems bei Herzinsuffizienz in erster Linie als Vasodilatator-Therapie aufgefaßt worden. Dementsprechend wurde die Rolle des bei Herzinsuffizienz aktivierten Renin-Angiotensin-Systems in der Erhöhung der hämodynamischen Belastung gesehen, hervorgerufen durch Vasokonstriktion und Volumenretention. Mittlerweile deuten vorliegende klinische und experimentelle Erfahrung auf zusätzliche wichtige Aspekte der ACE-Hemmung bei Herzinsuffizienz hin. Dazu gehören die Hemmung der erhöhten neuroendokrinen Aktivität und die Umkehrung oder Prävention von problematischen trophischen Reaktionen des überlasteten Myokards. Bei kardialer Überlast ist die intrakardiale Angiotensin-Bildung erhöht aufgrund einer vermehrten kardialen Expression von Angiotensinogen und von ACE sowie aufgrund von kardialer Akkumulation von zirkulierendem, nephrogenen aktiven Renin. Im menschlichen Myokard trägt zur intrakardialen Angiotensinbildung auch eine überwiegend aus Mastzellen stammende Chymase bei, die durch ACE-Inhibitoren nicht blockierbar ist.

Das bei kardialer Überlast vermehrt intrakardial gebildete Angiotensin trägt bei zu Koronarkonstriktion, Verzögerung der diastolischen Relaxation, Kardiozytenwachstum und interstitieller Fibrosierung, die die diastolische Funktionseinbuße verschlimmert. Ein wichtiges Problem in überlasteten, hypertrophierten Kardiozyten ist die Dedifferenzierung mit Instabilisierung der Ca++-Homöostase aufgrund von Änderungen der Genexperession. Dedifferenzierte Kardiozyten haben eine verminderte Expression der sarkoplasmatischen Ca++-ATPase und eine erhöhte Expression des sarkolemmalen Na+/Ca++-Austauschers. Daraus ergibt sich eine Abschwächung der „aktiven Diastole“ (i.e.: der Reakkumulation von Ca++ ins sarkoplasmatische Retikulum), eine abgeflachte Kraft-Frequenz-Beziehung, und eine besondere Anfälligkeit für fatale Arrhythmien. Außerdem erscheint ein erhöhtes lokales Renin-Angiotensin-System in dehnbaren Arterien des Herzens und des Kreislaufs zu einer verminderten Freisetzbarkeit von EDRF (endothelium-derived relaxing factor) zu führen, möglicherweise über eine Verminderung der lokalen Bradykininverfügbarkeit. Diese Modulation der Endothel-Funktion scheint zur Lokalisation und Progression der Entwicklung von arteriosklerotischen Läsionen beizutragen, falls Risikofaktoren der Arteriosklerose erhöht sind.

Schlüsselwörter

Kardiale Angiotensinbildung Myokardhypertrophie Kardiozytendedifferenzierung Ca++-Homöostase der Kardiozyten Ca++-ATPase des sarkoplasmatischen Reti-kulums Endothelfunktion 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • J. Holtz
    • 1
  1. 1.Institut für PathophysiologieMartin-Luther-Universität HalleDeutschland

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