Background--Although many studies suggested direct vasomotor effects of hydrogen peroxide (H₂O₂) in vitro, little is known about the vasomotor effects of H₂O₂ in vivo.

Methods and Results--We have generated mice overexpressing human catalase driven by the Tie-2 promoter to specifically target this transgene to the vascular tissue. Vessels of these mice (cat⁺⁺) expressed significantly higher levels of catalase mRNA, protein, and activity. The overexpression was selective for vascular tissue, as evidenced by immunohistochemistry in specimens of aorta, heart, lung, and kidney. Quantification of reactive oxygen species by fluorescence signals in cat⁺⁺ versus catalase-negative (catⁿ) mice showed a strong decrease in aortic endothelium and left ventricular myocardium but not in leukocytes. Awake male cat⁺⁺ at 3 to 4 months of age had a significantly lower systolic blood pressure (sBP, 102.7±2.2 mm Hg, n=10) compared with their transgene-negative littermates (catⁿ, 115.6±2.5 mm Hg, P=0.0211) and C57BL/6 mice (118.4±3.06 mm Hg, n=6). Treatment with the catalase inhibitor aminotriazole increased sBP of cat⁺⁺ to 117.3±4.3 mm Hg (P=0.0345), while having no effect in catⁿ (118.4±2.4 mm Hg, n=4, P>0.05). In contrast, treatment with the NO-synthase inhibitor nitro-L-arginine methyl ester (100 mg · kg BW^-1 · d^-1) increased sBP in cat⁺⁺ and C57Bl/6 to a similar extent. Likewise, phosphorylation of vasodilator-stimulated phosphoprotein in skeletal muscle, left ventricular myocardium, and lung was identical in cat⁺⁺ and catⁿ. Endothelium- and NO-dependent aortic vasodilations were unchanged in cat⁺⁺. Aortic KCl contractions were significantly lower in cat⁺⁺ and exogenous H₂O₂ (10 µmol/L)-induced vasoconstriction.

Conclusions--These data suggest that endogenous H₂O₂ may act as a vasoconstrictor in resistance vessels and contribute to the regulation of blood pressure.