Skip to Main content Skip to Navigation
Journal articles

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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [24 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00767049
Contributor : Matthieu Roustit <>
Submitted on : Wednesday, December 19, 2012 - 1:58:32 PM
Last modification on : Thursday, July 11, 2019 - 2:10:07 PM
Long-term archiving on: : Wednesday, March 20, 2013 - 11:36:25 AM

File

Roustit_Iontophoresis_of_endot...
Publisher files allowed on an open archive

Identifiers

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⟩

Share

Metrics

Record views

2343

Files downloads

844