Asymmetrisches Dimethylarginin (ADMA): Ein endogener Hemmstoff der NO-Synthase - und auch ein Risikomarker der Präeklampsie?

Zusammenfassung

Die Präeklampsie oder EPH-Gestose ist auch heute noch eine der wichtigsten Ursachen maternaler und neonataler Morbidität und Mortalität. Die Ursachen der Präeklampsie sind multifaktoriell, aber das Auftreten einer Präeklampsie ist häufig mit einer endothelialen Dysfunktion assoziiert. Das Gefäßendothel nimmt eine zentrale Stellung in der Aufrechterhaltung des physiologischen Gefäßtonus und der Gefäßstruktur ein; es ist auch für die Kreislaufanpassung an die Schwangerschaft mitverantwortlich. Einer der wichtigsten Mediatoren, die vom intakten Gefäßendothel freigesetzt werden, ist Stickstoffmonoxid (NO). Die Bildung von NO wird durch asymmetrisches Dimethylarginin (ADMA) gehemmt, ein Abkömmling der Aminosäure L-Arginin, der endogen vorkommt und dessen Plasmakonzentration in kardiovaskulären Risikokonstellationen ansteigt. In mehreren klinischen Studien wurde gezeigt, dass Präeklampsie-Patientinnen höhere ADMA-Spiegel aufweisen als gesunde Schwangere. Im Tierexperiment kann eine solche Hemmung der NO-Bildung eine Präeklampsie auslösen. Möglicherweise ist also ADMA ein neuer Marker eines erhöhten Präeklampsie-Risikos in der Schwangerschaft, ebenso wie es ein Marker eines erhöhten kardiovaskulären Risikos im Allgemeinen darstellt. Durch die Gabe von L-Arginin können die adversen Wirkungen von ADMA auf das Gefäßsystem aufgehoben werden; L-Arginin führte auch zur Senkung eines pathologisch erhöhten Blutdrucks bei schwangeren Frauen.

Abstract

Preeclampsia still is one of the major causes of maternal and neonatal morbidity and death. The causes of preeclampsia are multifactorial, but a common pathway of vascular impairment in preeclampsia is endothelial dysfunction. The endothelium plays a crucial role in regulating physiological vascular tone and structure as well as in the vascular adaptations to pregnancy. The major mediator responsible for this is nitric oxide (NO). NO formation is inhibited by asymmetric dimethylarginine (ADMA), an endogenous analogue of L-arginine. ADMA plasma levels are increased in patients at high cardiovascular risk. Several clinical studies have produced evidence to show that preeclampsia is associated with elevated ADMA plasma concentrations as compared to healthy pregnant women. In animal models, preeclampsia can be incuced by administration of NO synthase inhibitors. Therefore, ADMA may be a novel marker of the risk of preeclampsia, like it is a marker of cardiovascular risk in general. Administration of L-arginine can antagonize the adverse effects of ADMA on the vasculature; L-arginine has also been shown to reduce elevated blood pressure in pregnant women.

Schlüsselwörter

Endothel - L‐Arginin - Schwangerschaft - Risikomarker - Herz‐Kreislauf‐Erkrankungen

Key words

endothelium - L‐arginine - pregnancy - risk marker - cardiovascular disease

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