Ketteler M, Abou-Rebyeh F, Frey A, Gawlik A, Peters H, Westenfeld R, Distler A
Abteilung für Allgemeine Innere Medizin and Nephrologie, Universitätsklinikum Benjamin Franklin, Berlin.
Med Klin (Munich). 1998 Jan 15;93(1):15-21. doi: 10.1007/BF03045035.
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 (ecNOS) 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.
Modulation of the renal L-arginine/NO-system represents a promising therapeutic target in the treatment of acute an chronic kidney diseases.
一氧化氮(NO)是一种具有多种生物学效应的小分子气体。NO由一氧化氮合酶(NOS)从半必需氨基酸L-精氨酸生成。在肾脏中,定位于致密斑的神经元型NOS(bNOS)和内皮型NOS(ecNOS)参与肾小球血流动力学的调节。这些酶功能异常可能导致肾小球高血压和肾小球内血小板聚集增加。通过诱导型NOS同工型(iNOS)的激活可实现高组织浓度的NO生成,并且在免疫介导的肾脏疾病中,NO可能作为炎症的强效介质。因此,选择性抑制iNOS可能成为治疗肾小球肾炎的一种新型抗炎方法。基于实验数据,本文总结了NO及L-精氨酸的其他代谢产物在肾脏疾病病理生理学和治疗中的潜在重要性。
调节肾脏L-精氨酸/NO系统是治疗急慢性肾脏疾病的一个有前景的治疗靶点。