Titre
Endothelin, angiotensin II and adenosine in acute cyclosporine A nephrotoxicity.
Type
article
Institution
Externe
Périodique
Auteur(s)
Prévot, A.
Auteure/Auteur
Semama, D.S.
Auteure/Auteur
Tendron, A.
Auteure/Auteur
Justrabo, E.
Auteure/Auteur
Guignard, J.P.
Auteure/Auteur
Gouyon, J.B.
Auteure/Auteur
Liens vers les personnes
ISSN
0931-041X
Statut éditorial
Publié
Date de publication
2000
Volume
14
Numéro
10-11
Première page
927
Dernière page/numéro d’article
934
Peer-reviewed
Oui
Langue
anglais
Résumé
We previously developed a model of acute cyclosporine A (CsA)-induced vasomotor nephrotoxicity in rabbits. In the present study, we evaluated the role of endothelin (ET), angiotensin II (AII) and adenosine in this experimental model. All animals received CsA (25 mg/kg/day) for 5 days. Renal function parameters were first measured in a 30-min period, showing renal insufficiency in all animals. Then, rabbits were administered bosentan (10 mg/kg; antagonist of ET(AB) receptors), perindopril (20 microg/kg; angiotensin-converting enzyme inhibitor), or theophylline (1 mg/kg; adenosine receptor blocker at micromolar concentrations). After a 40-min equilibration period, renal function was assessed again for 30 min. Bosentan, perindopril and theophylline significantly reduced renal vascular resistance (-28+/-5%, -39+/-7% and -8+/-3%, respectively), and improved renal blood flow (+38+/-15%, +66+/-16% and +20+/-5%), glomerular filtration rate (+33+/-9%, +52+/-13% and +50+/-8%) and diuresis (+48+/-9%, +76+/-19% and +73+/-14%). Filtration fraction was unchanged with bosentan, decreased with perindopril (-10+/-9%) and increased with theophylline (+24+/-5%). The overall results suggest that ET, AII and adenosine are involved in the acute renal failure induced by CsA. We conclude that CsA administration for 5 days induced a vasomotor nephropathy with ET- and adenosine-mediated afferent arteriolar constriction as well as ET- and AII-mediated efferent arteriolar constriction.
Sujets
PID Serval
serval:BIB_C25A8B21E7DD
PMID
Date de création
2009-07-20T12:33:54.404Z
Date de création dans IRIS
2025-05-21T03:59:05Z