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Updated: Feb 27, 2026
Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models
Published on: October 22, 2012
Genetic Deletion of NADPH Oxidase 1 Rescues Microvascular Function in Mice With Metabolic Disease
Jennifer A Thompson1, Sebastian Larion1, James D Mintz1
1From the Vascular Biology Center (J.A.T., S.L., J.D.M., E.J.B.d.C., D.J.F., D.W.S.), Department of Physiology (D.W.S), Department of Pharmacology (D.J.F.), and Department of Medicine (S.L., E.J.B.d.C.), Augusta University, GA.
Rationale:
Early vascular changes in metabolic disease that precipitate the development of cardiovascular complications are largely driven by reactive oxygen species accumulation, yet the extent to which excess reactive oxygen species derive from specific NADPH oxidase isoforms remains ill defined.
Objective:
Identify the role of Nox1 in the development of microvascular dysfunction in metabolic disease.
Methods And Results:
Four genotypes were generated by breeding Nox1 knockout mice with db/db mice: lean (HdbWnox1), lean Nox1 knockout (HdbKnox1), obese (KdbWnox1), and obese KK (KdbKnox1). The degree of adiposity, insulin resistance, and dyslipidemia in KW mice was not influenced by Nox1 deletion as determined by nuclear magnetic resonance spectroscopy, glucose tolerance tests, and plasma analyses. Endothelium-dependent responses to acetylcholine in pressurized mesenteric arteries were reduced in KW versus HW (P<0.01), whereas deletion of Nox1 in KW mice normalized dilation. Vasodilator responses after inhibition of NO synthase blunted acetylcholine responses in KK and lean controls, but had no impact in KW, attributing recovered dilatory capacity in KK to normalization of NO. Acetylcholine responses were improved (P<0.05) with Tempol, and histochemistry revealed oxidative stress in KW animals, whereas Tempol had no impact and reactive oxygen species staining was negligible in KK. Blunted dilatory responses to an NO donor and loss of myogenic tone in KW animals were also rescued with Nox1 deletion.
Conclusions:
Nox1 deletion reduces oxidant load and restores microvascular health in db/db mice without influencing the degree of metabolic dysfunction. Therefore, targeted Nox1 inhibition may be effective in the prevention of vascular complications.
Insights
Targeting NADPH oxidase 1 (Nox1) reduces oxidative stress and improves microvascular function in metabolic disease, independent of metabolic changes. This suggests Nox1 inhibition can prevent vascular complications.
Area of Science:
- Vascular Biology
- Metabolic Disease
- Oxidative Stress
Background:
- Cardiovascular complications in metabolic disease stem from early vascular changes driven by reactive oxygen species (ROS).
- The specific NADPH oxidase (NADPHOX) isoforms contributing to excess ROS in metabolic disease are not fully understood.
- NADPHOX family, including Nox1, are key sources of cellular ROS.
Purpose of the Study:
- To investigate the role of Nox1 in the development of microvascular dysfunction in a mouse model of metabolic disease.
- To determine if Nox1 deletion impacts metabolic parameters such as adiposity, insulin resistance, and dyslipidemia.
Main Methods:
- Generated four mouse genotypes by breeding Nox1 knockout mice with db/db mice (lean, lean Nox1 knockout, obese, obese Nox1 knockout).
- Assessed adiposity, insulin resistance, and dyslipidemia using nuclear magnetic resonance spectroscopy, glucose tolerance tests, and plasma analyses.
- Evaluated endothelium-dependent responses in mesenteric arteries and responses to nitric oxide (NO) donors, with and without NO synthase inhibition and antioxidant treatment (Tempol).
Main Results:
- Nox1 deletion did not alter adiposity, insulin resistance, or dyslipidemia in obese mice.
- Microvascular dysfunction, characterized by reduced endothelium-dependent vasodilation, was observed in obese mice and normalized upon Nox1 deletion.
- Nox1 deletion restored nitric oxide (NO)-dependent vasodilation and myogenic tone in obese mice, indicating improved microvascular health.
- Antioxidant treatment (Tempol) improved vasodilation in obese mice, confirming the role of oxidative stress, which was reduced by Nox1 deletion.
Conclusions:
- Nox1 deletion effectively reduces the oxidant load and restores microvascular health in a mouse model of metabolic disease.
- The beneficial vascular effects of Nox1 deletion occur independently of improvements in metabolic dysfunction.
- Targeted inhibition of Nox1 presents a potential therapeutic strategy for preventing vascular complications associated with metabolic disease.
