Extracellular superoxide dismutase is a major determinant of nitric oxide bioavailability: in vivo and ex vivo evidence from ecSOD-deficient mice.

Détails

ID Serval
serval:BIB_D172FFB48CCE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Extracellular superoxide dismutase is a major determinant of nitric oxide bioavailability: in vivo and ex vivo evidence from ecSOD-deficient mice.
Périodique
Circulation research
Auteur(s)
Jung O., Marklund S.L., Geiger H., Pedrazzini T., Busse R., Brandes R.P.
ISSN
1524-4571[electronic]
Statut éditorial
Publié
Date de publication
2003
Volume
93
Numéro
7
Pages
622-9
Langue
anglais
Notes
Publication types: In Vitro ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
The bioavailability of nitric oxide (NO) within the vascular wall is limited by superoxide anions (O2.-). The relevance of extracellular superoxide dismutase (ecSOD) for the detoxification of vascular O2.- is unknown. We determined the involvement of ecSOD in the control of blood pressure and endothelium-dependent responses in angiotensin II-induced hypertension and renovascular hypertension induced by the two-kidney, one-clip model in wild-type mice and mice lacking the ecSOD gene. Blood pressure was identical in sham-operated ecSOD+/+ and ecSOD-/- mice. After 6 days of angiotensin II-treatment and 2 and 4 weeks after renal artery clipping, blood pressure was significantly higher in ecSOD-/- than ecSOD+/+ mice. Recombinant ecSOD selectively decreased blood pressure in hypertensive ecSOD-/- mice, whereas ecSOD had no effect in normotensive and hypertensive ecSOD+/+ mice. Compared with sham-operated ecSOD+/+ mice, sham-operated ecSOD-/- mice exhibited attenuated acetylcholine-induced relaxations. These responses were further depressed in vessels from clipped animals. Vascular O2.-, as measured by lucigenin chemiluminescence, was higher in ecSOD-/- compared with ecSOD+/+ mice and was increased by clipping. The antioxidant tiron normalized relaxations in vessels from sham-operated and clipped ecSOD-/-, as well as from clipped ecSOD+/+ mice. In contrast, in vivo application of ecSOD selectively enhanced endothelium-dependent relaxation in vessels from ecSOD-/- mice. These data reveal that endogenous ecSOD is a major antagonistic principle to vascular O2.-, controlling blood pressure and vascular function in angiotensin II-dependent models of hypertension. ecSOD is expressed in such an abundance that even in situations of high oxidative stress no relative lack of enzyme activity occurs.
Mots-clé
Acetylcholine, Angiotensin II, Animals, Blood Pressure, Blotting, Western, Catalase, Dose-Response Relationship, Drug, Endothelium, Vascular, Female, Humans, Hypertension, Hypertension, Renovascular, Male, Mice, Mice, Knockout, Nitric Oxide, Nitroprusside, Phenylephrine, Recombinant Proteins, Superoxide Dismutase, Superoxides, Vasoconstrictor Agents, Vasodilation, Vasodilator Agents
Pubmed
Web of science
Création de la notice
25/01/2008 8:45
Dernière modification de la notice
20/08/2019 15:51
Données d'usage