Abstract
Protein levels and polymorphisms of p22phox 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 p22phox expression would alter vascular ROS production and hemodynamics by targeting p22phox expression to smooth muscle in transgenic (Tg)p22smc. mice. Aortas of Tgp22smc mice had increased p22phox and Nox1 protein levels and produced more Superoxide and H2O2. Surprisingly, endothelium-dependent relaxation and blood pressure in Tgp22smc mice were normal. Aortas of Tgp22smc 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 Tgp22smc mice. Both eNOS expression and NO production were normalized by infusion of the glutathione peroxidase mimetic ebselen or by crossing Tgp22smc 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 Tgp22smc 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 H2O2 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.
Original language | English (US) |
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Pages (from-to) | H7-H12 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 288 |
Issue number | 1 57-1 |
DOIs | |
State | Published - Jan 2005 |
Externally published | Yes |
Keywords
- Endothelium
- Nitric oxide
- Oxidant stress
- Transgenic animals
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)