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Hemodynamic and biochemical adaptations to vascular smooth muscle overexpression of p22phox in mice.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2005 Jan; Vol. 288 (1), pp. H7-12. Date of Electronic Publication: 2004 Oct 07. - Publication Year :
- 2005
-
Abstract
- Protein levels and polymorphisms of p22(phox) have been suggested to modulate vascular NAD(P)H oxidase activity and vascular production of reactive oxygen species (ROS). We sought to determine whether increasing p22(phox) expression would alter vascular ROS production and hemodynamics by targeting p22(phox) expression to smooth muscle in transgenic (Tg) mice. Aortas of Tg(p22smc) mice had increased p22(phox) and Nox1 protein levels and produced more superoxide and H(2)O(2). Surprisingly, endothelium-dependent relaxation and blood pressure in Tg(p22smc) mice were normal. Aortas of Tg(p22smc) mice produced twofold more nitric oxide (NO) at baseline and sevenfold more NO in response to calcium ionophore as detected by electron spin resonance. Western blot analysis revealed a twofold increase in endothelial NO synthase (eNOS) protein expression in Tg(p22smc) mice. Both eNOS expression and NO production were normalized by infusion of the glutathione peroxidase mimetic ebselen or by crossing Tg(p22smc) mice with mice overexpressing catalase. We have previously found that NO stimulates extracellular superoxide dismutase (ecSOD) expression in vascular smooth muscle. In keeping with this, aortic segments from Tg(p22smc) mice expressed twofold more ecSOD, and chronic treatment with the NOS inhibitor N(G)-nitro-L-arginine methyl ester normalized this, suggesting that NO regulates ecSOD protein expression in vivo. These data indicate that chronic oxidative stress caused by excessive H(2)O(2) production evokes a compensatory response involving increased eNOS expression and NO production. NO in turn increases ecSOD protein expression and counterbalances increased ROS production leading to the maintenance of normal vascular function and hemodynamics.
- Subjects :
- Animals
Hemodynamics
Hydrogen Peroxide metabolism
Mice
Mice, Transgenic
Muscle, Smooth, Vascular metabolism
NADPH Oxidases
Nitric Oxide biosynthesis
Nitric Oxide Synthase metabolism
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Superoxide Dismutase metabolism
Adaptation, Physiological
Membrane Transport Proteins metabolism
Muscle, Smooth, Vascular blood supply
Muscle, Smooth, Vascular physiology
NADPH Dehydrogenase metabolism
Phosphoproteins metabolism
Reactive Oxygen Species metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 288
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 15471976
- Full Text :
- https://doi.org/10.1152/ajpheart.00637.2004