Iontophoresis of endothelin receptor antagonists in rats and men.

Abstract : INTRODUCTION: The treatment of scleroderma-related digital ulcers is challenging. The oral endothelin receptor antagonist (ERA) bosentan has been approved but it may induce liver toxicity. The objective of this study was to test whether ERAs bosentan and sitaxentan could be locally delivered using iontophoresis. METHODS: Cathodal and anodal iontophoresis of bosentan and sitaxentan were performed on anaesthetized rat hindquarters without and during endothelin-1 infusion. Skin blood flow was quantified using laser-Doppler imaging and cutaneous tolerability was assessed. Iontophoresis of sitaxentan (20 min, 20 or 100 µA) was subsequently performed on the forearm skin of healthy men (n = 5). RESULTS: In rats neither bosentan nor sitaxentan increased skin blood flux compared to NaCl. When simultaneously infusing endothelin-1, cathodal iontophoresis of sitaxentan increased skin blood flux compared to NaCl (AUC(0-20) were 44032.2 ± 12277 and 14957.5 ± 23818.8 %BL.s, respectively; P = 0.01). In humans, sitaxentan did not significantly increase skin blood flux as compared to NaCl. Iontophoresis of ERAs was well tolerated both in animals and humans. CONCLUSIONS: This study shows that cathodal iontophoresis of sitaxentan but not bosentan partially reverses endothelin-induced skin vasoconstriction in rats, suggesting that sitaxentan diffuses into the dermis. However, sitaxentan does not influence basal skin microvascular tone in rats or in humans.
Type de document :
Article dans une revue
PLoS ONE, Public Library of Science, 2012, 7 (7), pp.e40792. 〈10.1371/journal.pone.0040792〉
Liste complète des métadonnées

Littérature citée [24 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00767049
Contributeur : Matthieu Roustit <>
Soumis le : mercredi 19 décembre 2012 - 13:58:32
Dernière modification le : jeudi 30 novembre 2017 - 09:16:50
Document(s) archivé(s) le : mercredi 20 mars 2013 - 11:36:25

Fichier

Roustit_Iontophoresis_of_endot...
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

UGA

Citation

Matthieu Roustit, Sophie Blaise, Claire Arnaud, Marcin Hellmann, Claire Millet, et al.. Iontophoresis of endothelin receptor antagonists in rats and men.. PLoS ONE, Public Library of Science, 2012, 7 (7), pp.e40792. 〈10.1371/journal.pone.0040792〉. 〈inserm-00767049〉

Partager

Métriques

Consultations de la notice

599

Téléchargements de fichiers

406