Einfluss von L-Arginin auf die Arterioskleroseentwicklung: Was ist therapeutisch gesichert?

Zusammenfassung

L-Arginin ist das Substrat für das Enzym Stickstoffmonoxidsynthase (NOS), welches für die Produktion von Stickstoffmonoxid (NO) verantwortlich ist. Stickstoffmonoxid ist ein endogenes Molekül, das eine zentrale Rolle in der Regulation von Gefäßtonus und Gefäßstruktur spielt und an vielen Prozessen beteiligt ist, die während der Entwicklung der Atherosklerose ablaufen. Es ist gezeigt worden, dass sowohl die akute als auch die chronische Gabe von L-Arginin die Endothelfunktion in Tiermodellen mit Hypercholesterinämie und Atherosklerose verbessern kann. Studien haben gezeigt, dass die diätetische Gabe von L-Arginin die NO-Bildung beim Menschen steigern kann und dadurch letztlich die Gefäßgesundheit verbessert werden kann. In dem vorliegenden Artikel wird eine Übersicht über die Studienergebnisse mit intravenöser und oraler Gabe von L-Arginin beim Menschen gegeben, die ein breites Spektrum von Dosierungen, Studiendauer und Surrogatparametern für die Endothelfunktion widerspiegeln. Die Pharmakokinetik von L-Arginin wurde untersucht, Nebenwirkungen sind selten, meistens ungefährlich und dosisabhängig. Verschiedene mögliche Wirkungsmechanismen von L-Arginin werden vorgestellt. Abschließend wird eine Bewertung von L-Arginin als Therapeutikum aus der Sicht der Klinischen Pharmakologie gegeben.

Summary

L-arginine is the substrate for the enzyme nitric oxide synthase (NOS), which is responsible for the production of nitric oxide (NO), an endogenous messenger molecule involved in many of the processes associated with the development of atherosclerosis. Acute and chronic administration of L-arginine has been shown to improve endothelial function in animal models of hypercholesterolemia and atherosclerosis. Therefore, a lot of studies were conducted to elucidate whether dietary L-arginine supplementation can augment NO production in man and thereby improve vascular health. In this review the results of studies of intravenous and oral L-arginine supplementation with a colorful spectrum of doses, study duration and surrogate parameters of endothelial function are summarized. The pharmacokinetics of L-arginine have been investigated, side effects are rare and mostly mild and dose-dependent. Several possible mechanisms of action of L-arginine are discussed. An assessment of L-arginine as a therapeutic agent from the point of view of a clinical pharmacologist is given.

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