Reduction of pressor response to vasoconstrictor agents by overexpression of catalase in mice

Background: Hydrogen peroxide (H₂O₂) has been shown to induce vascular smooth muscle cell contraction in vitro. In this study, the effect of endogenously produced H₂O₂ on blood pressure (BP) was examined using a transgenic mouse model (hCatTg^+/0) in which catalase is over-expressed. Methods: The hCatTg^+/0 and wild-type mice received a bolus injection of norepinephrine (NE; 1 μg/g) or angiotensin II (Ang II; 0.5 μg/g), or an osmotic minipump infusion of NE (2.5 μg/g/day) or Ang II (0.5 μg/g/day) for 7 days. Systolic BP (SBP) was measured using a tail-cuff apparatus. H₂O₂ release from mouse aortas was measured using an H₂O₂ assay kit. Results: The hCatTg^+/0 and wild-type mice showed similar basal levels of systolic BP (SBP) and H₂O₂ release from the aorta. A bolus injection of NE or Ang II increased SBP 31 ± 5 and 37 ± 6 mm Hg, respectively, in wild-type mice. In contrast, same doses of NE and Ang II increased SBP only 15 ± 3 and 17 ± 4 mm Hg, respectively, in hCatTg^+/0 mice. Osmotic minipump infusion of NE or Ang II increased SBP by approximately 30 mm Hg in wild-type mice, but only by about 10 mm Hg in hCatTg^+/0 mice. The addition of NE or Ang II to the incubation media significantly increased H₂O₂ release from the aortic segment of wild-type mice but did not alter H₂O₂ release from the aortic segment of hCatTg^+/0 mice. Conclusion: Overexpression of catalase diminishes the pressor response to NE and Ang II by reducing H₂O₂ production in the arterial wall.