gp91phox-containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension

Détails

ID Serval
serval:BIB_29F1C67AD902
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
gp91phox-containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension
Périodique
Circulation
Auteur(s)
Jung  O., Schreiber  J. G., Geiger  H., Pedrazzini  T., Busse  R., Brandes  R. P.
ISSN
1524-4539 (Electronic)
Statut éditorial
Publié
Date de publication
04/2004
Volume
109
Numéro
14
Pages
1795-801
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr 13
Résumé
BACKGROUND: Isoforms of the NADPH oxidase contribute to vascular superoxide anion (*O2-) formation and limit NO bioavailability. We hypothesized that the endothelial gp91phox-containing NADPH oxidase is predominant in generating the O2- to scavenge endothelial NO and thus is responsible for the development of endothelial dysfunction. METHODS AND RESULTS: Endothelial dysfunction was studied in aortic rings from wild-type (WT) and gp91phox-knockout (gp91phox-/-) mice with and without renovascular hypertension induced by renal artery clipping (2K1C). Hypertension induced by 2K1C was more severe in WT than in gp91phox-/- mice (158+/-2 versus 149+/-2 mm Hg; P<0.05). Endothelium-dependent relaxation to acetylcholine (ACh) was attenuated in rings from clipped WT but not from clipped gp91phox-/- mice. The reactive oxygen species (ROS) scavenger Tiron, PEG-superoxide dismutase, and the NADPH oxidase inhibitory peptide gp91ds-tat enhanced ACh-induced relaxation in aortae of clipped WT mice. Inhibition of protein kinase C, Rac, and the epidermal growth factor receptor kinase, elements involved in the activation of the NADPH oxidase, restored normal endothelium-dependent relaxation in vessels from clipped WT mice but had no effect on relaxations in those from gp91phox-/- mice. Relaxations to exogenous NO were attenuated in vessels from clipped WT but not clipped gp91phox-/- mice. After removal of the endothelium or treatment with PEG-superoxide dismutase, NO-induced relaxations were identical in vessels from clipped and sham-operated WT and gp91phox mice. CONCLUSIONS: These data indicate that the formation of O2- by the endothelial gp91phox-containing NADPH oxidase accounts for the reduced NO bioavailability in the 2K1C model and contributes to the development of renovascular hypertension and endothelial dysfunction.
Mots-clé
Acetylcholine/pharmacology Angiotensin II/blood Animals Antioxidants/pharmacology Aorta Bacterial Toxins/pharmacology Cardiomyopathy, Hypertrophic/etiology Cytochromes b/deficiency/genetics/*physiology Disease Models, Animal Endothelium, Vascular/*enzymology/physiopathology Enzyme Inhibitors/pharmacology Glycoproteins/pharmacology Hypertension, Renovascular/complications/*enzymology/physiopathology Indoles/pharmacology Male Membrane Glycoproteins Mice Mice, Inbred C57BL Mice, Knockout NADPH Oxidase Nitric Oxide/*metabolism Organ Culture Techniques Polyethylene Glycols/pharmacology Protein Kinase C/antagonists & inhibitors Protein-Serine-Threonine Kinases/antagonists & inhibitors Proto-Oncogene Proteins c-akt Receptor, Epidermal Growth Factor/antagonists & inhibitors Superoxide Dismutase/pharmacology Superoxides/*metabolism Tiron/pharmacology Tyrphostins/pharmacology Vasodilation/drug effects Vasodilator Agents/pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 8:45
Dernière modification de la notice
20/08/2019 13:09
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