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Role of endogenous endothelin in endothelial dysfunction in murine model of systemic sclerosis: tight skin mice 1.
Fundam Clin Pharmacol. 2008 Dec; 22(6):649-55.FC

Abstract

Systemic sclerosis (SSc) is a systemic inflammatory disorder, resulting in severe vascular dysfunction. The endothelin (ET) system has vasoconstrictor and profibrotic properties and has been shown to be activated in SSc. ET antagonists are currently used in SSc-related pulmonary arterial hypertension, but the endothelial impact of ET antagonists remains less known in SSc. We thus assessed the effects of the dual ET(A)-ET(B) antagonist, bosentan, on endothelial dysfunction in a murine model of SSc, the heterozygous tight-skin mice 1 (TSK1(+)). Six-week-old TSK1(+) were either untreated or treated for 6 weeks with bosentan (100 mg/kg/day), and compared with controls. Endothelial function was evaluated in isolated mesenteric resistance arteries, using a small vessel myograph. TSK1(+) displayed endothelial dysfunction, as shown by a decreased response of mesenteric arteries to acetylcholine, especially in the presence of L-nitro-arginine methyl ester (L-NAME), corresponding to NO-independent, prostaglandin-mediated relaxation. The NO-independent relaxation was partially restored in bosentan-treated TSK1(+), and this was abolished by a cyclo-oxygenase inhibitor. Therefore, the murine model of SSc, TSK1(+) exhibits severe endothelial dysfunction of peripheral resistance arteries. The ET antagonist bosentan prevents endothelial alterations, suggesting a major role of ET in the adverse vascular effects of SSc.

Authors+Show Affiliations

Inserm U644 & Rouen University Hospital, Institute for Biomedical Research and IFRMP 23, University of Rouen, Rouen, France. vincent.richard@univ-rouen.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19049669

Citation

Richard, Vincent, et al. "Role of Endogenous Endothelin in Endothelial Dysfunction in Murine Model of Systemic Sclerosis: Tight Skin Mice 1." Fundamental & Clinical Pharmacology, vol. 22, no. 6, 2008, pp. 649-55.
Richard V, Solans V, Favre J, et al. Role of endogenous endothelin in endothelial dysfunction in murine model of systemic sclerosis: tight skin mice 1. Fundam Clin Pharmacol. 2008;22(6):649-55.
Richard, V., Solans, V., Favre, J., Henry, J. P., Lallemand, F., Thuillez, C., & Marie, I. (2008). Role of endogenous endothelin in endothelial dysfunction in murine model of systemic sclerosis: tight skin mice 1. Fundamental & Clinical Pharmacology, 22(6), 649-55. https://doi.org/10.1111/j.1472-8206.2008.00634.x
Richard V, et al. Role of Endogenous Endothelin in Endothelial Dysfunction in Murine Model of Systemic Sclerosis: Tight Skin Mice 1. Fundam Clin Pharmacol. 2008;22(6):649-55. PubMed PMID: 19049669.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of endogenous endothelin in endothelial dysfunction in murine model of systemic sclerosis: tight skin mice 1. AU - Richard,Vincent, AU - Solans,Violaine, AU - Favre,Julie, AU - Henry,Jean-Paul, AU - Lallemand,Françoise, AU - Thuillez,Christian, AU - Marie,Isabelle, PY - 2008/12/4/pubmed PY - 2009/2/20/medline PY - 2008/12/4/entrez SP - 649 EP - 55 JF - Fundamental & clinical pharmacology JO - Fundam Clin Pharmacol VL - 22 IS - 6 N2 - Systemic sclerosis (SSc) is a systemic inflammatory disorder, resulting in severe vascular dysfunction. The endothelin (ET) system has vasoconstrictor and profibrotic properties and has been shown to be activated in SSc. ET antagonists are currently used in SSc-related pulmonary arterial hypertension, but the endothelial impact of ET antagonists remains less known in SSc. We thus assessed the effects of the dual ET(A)-ET(B) antagonist, bosentan, on endothelial dysfunction in a murine model of SSc, the heterozygous tight-skin mice 1 (TSK1(+)). Six-week-old TSK1(+) were either untreated or treated for 6 weeks with bosentan (100 mg/kg/day), and compared with controls. Endothelial function was evaluated in isolated mesenteric resistance arteries, using a small vessel myograph. TSK1(+) displayed endothelial dysfunction, as shown by a decreased response of mesenteric arteries to acetylcholine, especially in the presence of L-nitro-arginine methyl ester (L-NAME), corresponding to NO-independent, prostaglandin-mediated relaxation. The NO-independent relaxation was partially restored in bosentan-treated TSK1(+), and this was abolished by a cyclo-oxygenase inhibitor. Therefore, the murine model of SSc, TSK1(+) exhibits severe endothelial dysfunction of peripheral resistance arteries. The ET antagonist bosentan prevents endothelial alterations, suggesting a major role of ET in the adverse vascular effects of SSc. SN - 1472-8206 UR - https://www.unboundmedicine.com/medline/citation/19049669/Role_of_endogenous_endothelin_in_endothelial_dysfunction_in_murine_model_of_systemic_sclerosis:_tight_skin_mice_1_ L2 - https://doi.org/10.1111/j.1472-8206.2008.00634.x DB - PRIME DP - Unbound Medicine ER -