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Stickstoffmonoxid, L-Arginin und die Niere

No, L-arginine and the kidney: Experimental studies to novel therapeutic approaches

Experimentelle Studien zu neuen Therapieansätzen

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Zusammenfassung

□ Hintergrund

Stickstoffmonoxid (NO) ist ein gasförmiges, biologisches Effektormolekül mit multiplen Wirkungen. NO wird durch sogenannte NO-Synthasen (NOS) von der semi-essentiellen Aminosäure L-Arginin gebildet. In der Niere spielen die in der Macula densa lokalisierte neuronale NOS (bNOS) und die endotheliale NOS (ecNOS) eine bedeutsame Rolle in der Regulation der glomerulären Hämodynamik. Eine gestörte Funktion dieser beiden Enzyme könnte einen glomerulären Hochdruck und eine gesteigerte intraglomeruläre Thrombozytenaggregation zur Folge haben. Eine NO-Produktion in hohen Gewebekonzentrationen kann durch die induzierbare NOS-Isoform (iNOS) erreicht werden und scheint hingegen ein potenter Inflammationsmediator bei primär entzündlichen Nierenerkrankungen zu sein. Die selektive Hemmung der iNOS könnte zukünftig ein neues, antiinflammatorisches Therapieprinzip zum Beispiel in der Glomerulonephritisbehandlung werden. Im folgenden soll anhand von überwiegend experimentellen Daten die Bedeutung von NO, aber auch anderer Metaboliten der Aminosäure L-Arginin, für die Pathophysiologie und therapeutische Beeinflussung von Nierenkrankheiten dargestellt werden.

□ Schlußfolgerung

Die Modulation des renalen L-Arginin/NO-Systems repräsentiert einen vielversprechenden Therapieansatz bei akuten und chronischen Nierenkrankheiten.

Summary

□ Background

Nitric oxide (NO) is a small gaseous, molecule with multiple biological effects. NO is produced from the semi-essential amino acid L-arginine by NO synthases (NOS). In the kidney, neuronal NOS (bNOS), which is localized in the macula densa, and endothelial NOS (ec NOS) are involved in the regulation of glomerular hemodynamics. Dysfunction of these enzymes may cause glomerular hypertension and increased intraglomerular platelet aggregation. NO production in high tissue concentrations can be achieved by activation of an inducible NOS isoform (iNOS) and may act as a potent mediator of inflammation in immune-mediated renal diseases. Selective inhibition of iNOS may, therefore, become a novel anti-inflammatory approach in the treatment of glomerulonephritis. Based on experimental data, the potential importance of NO and other metabolites of L-arginine in the pathophysiology and therapy of renal diseases is summarized in this article.

□ Conclusion

Modulation of the renal L-arginine/NO-system represents a promising therapeutic target in the treatment of acute an chronic kidney diseases.

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  1. Abteilung für Allgemeine Innere Medizin und Nephrologie, Universitätsklinikum Benjamin Franklin, Hindenburgdamm 30, D-12200, Berlin

    Markus Ketteler, Faikah Abou-Rebyeh, Alexander Frey, Alexander Gawlik, Harm Peters, Ralf Westenfeld & Armin Distler

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Ketteler, M., Abou-Rebyeh, F., Frey, A. et al. Stickstoffmonoxid, L-Arginin und die Niere. Med. Klin. 93, 15–21 (1998). https://doi.org/10.1007/BF03045035

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