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Die Bedeutung von Eicosanoiden bei glomerulären Erkrankungen

Eicosanoids and glomerular disease

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Summary

Prostanoids are local cyclooxygenase products, synthesized by mesangial and epithelial cells of the glomerulus as well as by a variety of inflammatory cells and platelets. Prostaglandins and thromboxane have direct vasodilatory and vasoconstrictory effects and can modulate glomerular function. Arachidonic acid, the main substrate for cyclooxygenase, can also be metabolized by the lipoxygenase pathway to leukotrienes, substances which are primarily synthesized in inflammatory cells.

In several models induction of immunologic glomerular injury is associated with an increased glomerular formation of cyclooxygenase and lipoxygenase products. The changes in cyclooxygenase products have been shown to account for some hemodynamic changes found in some of these models. Increased renal prostanoid formation is also present in patients with glomerular disease. There is some evidence that increased renal PG-formation in patients with moderate glomerular disease regulates GFR and mediates proteinurie in some of these patients. Leukotrienes are chemotactive substances which modulate the function of inflammatory cells, stimulate the growth of mesangial cells, and constrict mesangial cells in culture. Thus, these compounds might be mediators in the induction of immune mediated glomerular disease.

Zusammenfassung

Eicosanoide sind Syntheseprodukte der Zyklooxygenase und Lipoxygenase, Enzymkomplexe, die in fast allen Körperzellen vorkommen und ihr Hauptsubstrat, die mehrfach ungesättigte Arachidonsäure (AS), verstoffwechseln. Prostaglandine (PG) E2, I2 und Thromboxan (Tx) A2 sind Zyklooxygenaseprodukte mesangialer und epithelialer Zellen des Glomerulus, die direkte und indirekte vasodilatatorische und vasokonstriktorische Effekte am Glomerulus ausüben. Vasodilatatorische Prostaglandine E2 und I2 sind verantwortlich für die Aufrechterhaltung der GFR bei kritischer renaler Perfusion. Diese Prostanoide (PGE2 und PGI2) vermitteln darüberhinaus aber auch die glomeruläre Hyperperfusion nach experimenteller Nierenablation und bei Patienten mit chronischen Glomerulopathien. Die Induktion verschiedener tierexperimenteller Glomerulonephritiden steigert die glomeruläre PG- und Txsynthese. Der stimulatorische Einfluß auf den vasokostriktorischen Metaboliten TxA2 ist ausgeprägter als auf die Synthese der vasodilatatorischen PGE2 und I2. Einige Befunde weisen darauf hin, daß die erhöhte glomeruläre TxA2 Produktion mitverantwortlich ist für die reduzierte GFR, die bei experimentellen Nephritiden beobachtet wird. Bei einer Reihe von Glomerulopathien des Menschen ist die Produktion vasodilatatorischer Prostaglandine gesteigert. Die Gabe eines Zyklooxygenasehemmers führt bei diesen Patienten zur Reduktion der Proteinurie. Neben hämodynamischen Effekten scheint die erhöhte vasodilatatorische PG Produktion bei diesen Patienten auch die Permselektivität der glomerulären Filtrationsbarriere zu beeinflussen. Hauptsyntheseorte für Lipoxygenaseprodukte sind Granulozyten und Monozyten. Pharmakologische Untersuchungen zeigen, daß Lipoxygenaseprodukte (Leukotriene) vasokonstriktorische Effekte am Glomerulus haben. Leukotriene beeinflussen darüberhinaus das Wachstum mesangialer Zellen in Kultur und erhöhen die Adhäsion von Monozyten an mesangiale Zellen. Sie können deshalb bei zellvermittelten Glomerulonephritiden von Bedeutung sein.

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  1. Department of Medicine, Division of Nephrology, University of Washington, Seattle, USA

    R. A. K. Stahl

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Stahl, R.A.K. Die Bedeutung von Eicosanoiden bei glomerulären Erkrankungen. Klin Wochenschr 64, 813–823 (1986). https://doi.org/10.1007/BF01725553

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