Vascular hypertrophy in angiotensin II-induced hypertension is mediated by vascular smooth muscle cell-derived H2O2.
Angiotensin II induces the development of vascular hypertrophy and hypertension. An increasing number of studies have demonstrated that reactive oxygen species are involved in many of the vascular responses to angiotensin II. However, the role of specific cell types and the precise identity of the functionally relevant reactive oxygen species remain unclear. In this study, we established a line of transgenic mice with vascular smooth muscle cell (SMC)-specific overexpression of the human catalase gene to explicitly test the functional role of vascular smooth muscle-derived hydrogen peroxide in the hypertensive and hypertrophic responses to angiotensin II in vivo. Catalase overexpression was confirmed by increased expression of catalase mRNA and protein, as well as by an increase in catalase enzymatic activity. The catalase transgenic mice were viable, had no change in basal hydrogen peroxide release (0.36+/-0.03 versus 0.37+/-0.14 micromol/L), and showed no overt developmental abnormality. In response to angiotensin II treatment, catalase transgenic mice exhibited lower hydrogen peroxide release compared with control animals. There was no effect on the hypertensive response to angiotensin II (147+/-10 versus 148+/-12 mm Hg). However, angiotensin II-induced aortic wall hypertrophy was dramatically attenuated in the catalase transgenic mice (wall thickness 32.4+/-2.0 versus 43.2+/-7.6 microm; P<0.001). These results demonstrate that vascular SMC-derived hydrogen peroxide plays an important role in angiotensin II-induced hypertrophy of the arterial wall.
Zhang
Yong
Y
Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Griendling
Kathy K
KK
Dikalova
Anna
A
Owens
Gary K
GK
Taylor
W Robert
WR
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology*; D006984:Hypertrophy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D006861:Hydrogen Peroxide; D002374:Catalase