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Angiotensin II-induced hypertrophy is potentiated in mice overexpressing p22phox in vascular smooth muscle.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2005 Jan; Vol. 288 (1), pp. H37-42. Date of Electronic Publication: 2004 Sep 02. - Publication Year :
- 2005
-
Abstract
- Increased reactive oxygen species (ROS) are implicated in several vascular pathologies associated with vascular smooth muscle hypertrophy. In the current studies, we utilized transgenic (Tg) mice (Tg(p22smc)) that overexpress the p22(phox) subunit of NAD(P)H oxidase selectively in smooth muscle. These mice have a twofold increase in aortic p22(phox) expression and H(2)O(2) production and thus provide an excellent in vivo model in which to assess the effects of increased ROS generation on vascular smooth muscle cell (VSMC) function. We tested the hypothesis that overexpression of VSMC p22(phox) potentiates angiotensin II (ANG II)-induced vascular hypertrophy. Male Tg(p22smc) mice and negative littermate controls were infused with either ANG II or saline for 13 days. Baseline blood pressure was not different between control and Tg(p22smc) mice. ANG II significantly increased blood pressure in both groups, with this increase being slightly exacerbated in the Tg(p22smc) mice. Baseline aortic wall thickness and cross-sectional wall area were not different between control and Tg(p22smc) mice. Importantly, the ANG II-induced increase in both parameters was significantly greater in the Tg(p22smc) mice compared with control mice. To confirm that this potentiation of vascular hypertrophy was due to increased ROS levels, additional groups of mice were coinfused with ebselen. This treatment prevented the exacerbation of hypertrophy in Tg(p22smc) mice receiving ANG II. These data suggest that although increased availability of NAD(P)H oxidase-derived ROS is not a sufficient stimulus for hypertrophy, it does potentiate ANG II-induced vascular hypertrophy, making ROS an excellent target for intervention aimed at reducing medial thickening in vivo.
- Subjects :
- Animals
Aorta drug effects
Aorta metabolism
Aorta pathology
Blood Pressure drug effects
Drug Synergism
Hypertrophy
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Muscle, Smooth, Vascular drug effects
NADPH Oxidases
Angiotensin II pharmacology
Membrane Transport Proteins metabolism
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular pathology
NADPH Dehydrogenase metabolism
Phosphoproteins metabolism
Vasoconstrictor Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 288
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 15345488
- Full Text :
- https://doi.org/10.1152/ajpheart.00638.2004