Reduction of pressor response to vasoconstrictor agents by overexpression of catalase in mice.
BACKGROUND
Hydrogen peroxide (H(2)O(2)) has been shown to induce vascular smooth muscle cell contraction in vitro. In this study, the effect of endogenously produced H(2)O(2) on blood pressure (BP) was examined using a transgenic mouse model (hCatTg(+/0)) in which catalase is overexpressed.


METHODS
The hCatTg(+/0) and wild-type mice received a bolus injection of norepinephrine (NE; 1 microg/g) or angiotensin II (Ang II; 0.5 microg/g), or an osmotic minipump infusion of NE (2.5 microg/g/day) or Ang II (0.5 microg/g/day) for 7 days. Systolic BP (SBP) was measured using a tail-cuff apparatus. H(2)O(2) release from mouse aortas was measured using an H(2)O(2) assay kit.


RESULTS
The hCatTg(+/0) and wild-type mice showed similar basal levels of systolic BP (SBP) and H(2)O(2) 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 H(2)O(2) release from the aortic segment of wild-type mice but did not alter H(2)O(2) release from the aortic segment of hCatTg(+/0) mice.


CONCLUSIONS
Overexpression of catalase diminishes the pressor response to NE and Ang II by reducing H(2)O(2) production in the arterial wall.
Yang
Hong
H
Department of Anatomy and Physiology, Meharry Medical College, Nashville, Tennessee 37208, USA.
Shi
MingJian
M
VanRemmen
Holly
H
Chen
XinLian
X
Vijg
Jan
J
Richardson
Arlan
A
Guo
ZhongMao
Z
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002374:Catalase / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D006861:Hydrogen Peroxide; D002374:Catalase; D009638:Norepinephrine