Supplementary file 1_NADPH oxidase 4 as a source of hydrogen peroxide can regulate norepinephrine levels and vascular contraction.docx

In chromaffin cells, treatment with hydrogen peroxide stimulated catecholamine release and increased dopamine beta-hydroxylase expression, indicating a regulatory role of hydrogen peroxide in catecholamine synthesis and secretion. Further analysis of the physiological consequences of reduced norepinephrine levels in Nox4^−/− mice revealed decreased alpha-1 adrenergic receptor expression and impaired adrenergic vascular contraction, while cardiac function remained unaffected.

In a model of physical activity, Nox4 depletion resulted in smaller adrenal glands and lower urinary norepinephrine concentrations, further explaining diminished physical activity of Nox4^−/− mice.</p>Conclusion<p>Our findings provide evidence that Nox4-derived H₂O₂ plays a role in norepinephrine release and norepinephrine-mediated functions. Hence, loss of Nox4 impairs vascular contractility and reduces physical activity performance, highlighting the physiological importance of Nox4 in adrenal function.</p>