Nephrol Dial Transplant (2000) 15: 935-937
© 2000 European Renal Association-European Dialysis and Transplant Association
Editorial Comments
Transgenic animal models for the analysis of the renal endothelin system
1 Department of Nephrology, University Hospital Charité, Humboldt Universität zu Berlin and 2 Institute of Clinical Pharmacology and Toxicology, Benjamin Franklin Medical Center, Freie Universität Berlin, Berlin, Germany
The endothelin types
Endogenous peptidergic factors with vasoactive properties were first described by Hickey et al. in 1985 [1]. Yanagisawa and co-workers found that porcine endothelial cells generated a 21-aminoacid peptide, endothelin-1 in 1988 [2]. An i.v. injection of this new endothelium-derived peptide revealed that endothelin-1 (ET-1) is one of the most potent vasoconstrictors in vivo. Two further members of the ET family were described later and termed ET-2 and ET-3. Most studies on the ET system have focused on ET-1. Release of the active ET-1 peptide requires cleavage of a Trp21–Val22 bond in the carboxy terminal of the precursor molecule, big ET-1. This reaction is catalysed by a membrane-bound metalloprotease, ET-converting enzyme (ECE-1). ET synthesis is mainly regulated on the level of gene transcription when vasoconstrictor peptides, inflammatory cytokines, and physical factors (e.g. hypoxia and shear stress) act on the endothelium.
Endothelin and the kidney
Although the normal human kidney
The transgenic animal models
The knock-out animal models
What are the conclusions?
Notes
References
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