© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Endothelin blockers and renal protection: a new strategy to prevent end-organ damage in cardiovascular disease?
aDepartment of Nephrology and Hypertension, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, Netherlands
bDepartment of Internal Medicine, Bosch Medicentrum, Utrecht, Netherlands
cKendle/U-Gene Clinical Pharmacology Unit, Utrecht, Netherlands
* Corresponding author. Tel: +31-30-250-7329; Fax: +31-30-254-3492; E-mail: t.rabelink@digd.azu.nl
Received 19 March 1998; accepted 22 May 1998
| The first 150 words of the full text of this article appear below. |
| 1 Introduction |
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The endothelin (ET) family comprises three 21-amino acid peptides: ET-1, ET-2 and ET-3. Endothelin-1 has been identified as the major cardiovascular isopeptide. Release of the active peptide ET-1 requires cleavage of a Trp21–Val22 bond in the carboxyterminal of the precursor molecule, big ET-1 [1]. This reaction is catalyzed by a membrane bound metalloprotease, endothelin converting enzyme (ECE-1) [1, 2]. An intracellularly located ECE (ECE-2) has been identified as well [3]. Endothelin release is increased transcriptionally when the endothelium is exposed to vasoconstrictor peptides, inflammatory cytokines and physical factors (e.g. angiotensin II, thrombin, TGF-β). Although the human kidney contains mRNA for all three isoforms of endothelin (ET), ET-1 appears to be the only peptide expressed at the protein level [4]. Expression of ET-1, its precursor, big ET-1, and the ECE in the non-diseased kidney is largely confined to the glomerular and vascular endothelium [4, 5].
| 2 Chronic renal failure: a cardiovascular complication? |
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| 3 Is endothelin a mediator of diabetic nephropathy? |
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| 4 Is ET-1 a mediator of hypertensive renal disease? |
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| 5 Pharmacology of the endothelin system |
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| 6 Clinical countdown |
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6.1 Hemodynamic effects:
6.2 Interaction with the renin angiotensin system
| 7 Conclusion |
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