„Endogenes Digitalis” – der lange Weg vom herzwirksamen pflanzlichen Toxin zum Hormon der Säuger

W. Schoner; N. Bauer; G. Scheiner-Bobis

doi:10.1055/s-0037-1622553

Tierärztliche Praxis Ausgabe K: Kleintiere / Heimtiere, Table of Contents

Tierarztl Prax Ausg K Kleintiere Heimtiere 2006; 34(06): 389-397
DOI: 10.1055/s-0037-1622553

Allgemeines

Schattauer GmbH

„Endogenes Digitalis” – der lange Weg vom herzwirksamen pflanzlichen Toxin zum Hormon der Säuger

“Endogenous digitalis” – the long journey from a herbal cardiac toxin to a mammalian hormone

W. Schoner

¹Aus dem Institut für Biochemie und Endokrinologie (Prof. Dr. W. Schoner) und der, Fachbereich Veterinärmedizin der Justus-Liebig-Universität Gießen

,

N. Bauer

²Klinik für Kleintiere, Innere Medizin (Prof. Dr. R. Neiger), klinische Pathophysiologie und klinische Laboratoriumsdiagnostik (Prof. Dr. A. Moritz), Fachbereich Veterinärmedizin der Justus-Liebig-Universität Gießen

,

G. Scheiner-Bobis

¹Aus dem Institut für Biochemie und Endokrinologie (Prof. Dr. W. Schoner) und der, Fachbereich Veterinärmedizin der Justus-Liebig-Universität Gießen

› Author Affiliations

Abstract

Zusammenfassung

Endogene Herzglykoside wurden kürzlich aus Blut, Urin, Nebennieren und Hypothalamus von Säugetieren isoliert und in ihrer Struktur aufgeklärt. Zu den endogenen Herzglykosiden zählen so gut bekannte Hemmstoffe der Natriumpumpe wie Ouabain (g-Strophanthin), Digoxin und Marinobufagenin. Endogenes Ouabain und Digoxin werden in der Nebennierenrinde der Säuger aus Progesteron und Pregnenolon synthetisiert. Ouabain wird bei Kreislaufbelastung rasch freigesetzt, seine Konzentration fällt bei Ruhe innerhalb weniger Minuten wieder ab. ACEInhibitoren und β-Blocker verhindern bei Hunden diesen Anstieg. Ouabain wird durch ACTH, Adrenalin und Angiotensin II aus Nebennierenrindenzellen in Kultur freigesetzt. Nanomolare Ouabain-Konzentrationen stimulieren die Proliferation von glatten Muskelzellen. An schwerer dilatativer Kardiomyopathie erkrankte Hunde haben im Vergleich zu gesunden Hunden signifikant erniedrigte Ouabain-Blutwerte. Beim Menschen und Ratten führt eine lang dauernde zu hohe NaCl-Zufuhr über die Nahrung zum Konzentrationsanstieg von endogenem Ouabain im Blut und zum Bluthochdruck. Eine über lange Zeit durchgeführte Infusion von Ouabain, aber nicht von Digoxin, erzeugt bei Ratten Bluthochdruck. Digoxin senkt den Ouabain-induzierten Bluthochdruck. Da bei ca. 50% der Hochdruckpatienten erhöhte Ouabain-Werte vorliegen, ist es von großer medizinischer Bedeutung, dass mit dem Ouabain-Antagonisten Rostafuroxin ein neues Prinzip und eine neue Gruppe von Blutdrucksenkern gefunden wurde. Marinobufagenin, dessen Konzentration bei Herzinfarkt akut ansteigt, hat auf die Niere eine natriuretische Wirkung. Im Gehirn wird Ouabain im Hypothalamus synthetisiert und bei einer erhöhten intrazellulären Natriumkonzentration freigesetzt.

Summary

Endogenous cardiac glycosides were recently identified in blood, urine, adrenal glands and hypothalamus of mammals. Such endogenous cardiac glycosides are ouabain, digoxin and marinobufagenin, all well known inhibitors of the sodium pump. The compounds are synthesized in the adrenal cortex from progesterone and pregnenolone as precursors. Physical exercise leads to a rapid increase of ouabain and it declines within minutes upon rest. However, treatment with ACE-inhibitors and β-blockers abolishes this rise. Adrenal cortical cells release ouabain rapidly upon treatment with ACTH, angiotensin II and epinephrine. Nanomolar concentrations of ouabain stimulate the proliferation of smooth muscle cells and the release of endothelin 1 from endothelial cells. Dogs suffering from dilatative cardiomyopathy have reduced plasma concentrations of endogenous ouabain as compared to healthy dogs. Increased dietary exposition of humans and rats to NaCl results in a parallel increase of endogenous ouabain and arterial blood pressure. Long-term infusion of rats with nanomomolar concentrations of ouabain– but not digoxin– results in the development of arterial hypertension. However, digoxin lowers ouabain-induced hypertension. About 50% of the European population suffering from arterial hypertension show elevated concentrations of endogenous ouabain in blood plasma. Hence it is of considerable importance that rostafuroxin– an ouabain antagonist – effectively lowers blood pressure. Marinobufagenin which rises in blood plasma of human patients with cardiac infarction induces natriuresis. Ouabain is synthesized in the hypothalamus as well. It is released quite certainly in some areas of the brain upon intracellular rise of sodium.

Schlüsselwörter

endogenes Digitalis - endogenes Ouabain - endogenes Marinobufagenin - Kardiomyopathie - arterieller Bluthochdruck - Ouabain-Antagonist Rostafuroxin

Key words

Endogenous digitalis - endogenous ouabain - endogenous marinobufagenin - cardiomyopathy - arterial hypertension - ouabain antagonist rostafuroxin

Full Text

References

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