Journal article
Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat
American journal of physiology. Heart and circulatory physiology, Vol.294(6), pp.H2659-H2668
06/01/2008
DOI: 10.1152/ajpheart.00953.2007
PMID: 18424632
Abstract
The transgenic (mRen2)27 (Ren2) rat overexpresses mouse renin in extrarenal tissues, causing increased local synthesis of ANG II, oxidative stress, and hypertension. However, little is known about the role of oxidative stress induced by the tissue renin-angiotensin system (RAS) as a contributing factor in pulmonary hypertension (PH). Using male Ren2 rats, we test the hypothesis that lung tissue RAS overexpression and resultant oxidative stress contribute to PH and pulmonary vascular remodeling. Mean arterial pressure (MAP), right ventricular systolic pressure (RVSP), and wall thickness of small pulmonary arteries (PA), as well as intrapulmonary NADPH oxidase activity and subunit protein expression and reactive oxygen species (ROS), were compared in age-matched Ren2 and Sprague-Dawley (SD) rats pretreated with the SOD/catalase mimetic tempol for 21 days. In placebo-treated Ren2 rats, MAP and RVSP, as well as intrapulmonary NADPH oxidase activity and subunits (Nox2, p22(phox), and Rac-1) and ROS, were elevated compared with placebo-treated SD rats (P < 0.05). Tempol decreased RVSP (P < 0.05), but not MAP, in Ren2 rats. Tempol also reduced intrapulmonary NADPH oxidase activity, Nox2, p22phox, and Rac-1 protein expression, and ROS in Ren2 rats (P < 0.05). Compared with SD rats, the cross-sectional surface area of small PA was 38% greater (P < 0.001) and luminal surface area was 54% less (P < 0.001) in Ren2 rats. Wall surface area was reduced and luminal area was increased in tempol-treated SD and Ren2 rats compared with untreated controls (P < 0.05). Collectively, the results of this investigation support a seminal role for enhanced tissue RAS/oxidative stress as factors in development of PH and pulmonary vascular remodeling.
Details
- Title: Subtitle
- Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat
- Creators
- Vincent G. DeMarco - University of MissouriJavad Habibi - University of MissouriAdam T. Whaley-Connell - University of MissouriRebecca I. Schneider - University of MissouriRandall L. Heller - University of MissouriJames P. Bosanquet - University of MissouriMelvin R. Hayden - University of MissouriKimberly Delcour - University of MissouriS. A. Cooper - University of MissouriBradley T. Andresen - University of MissouriJames R. Sowers - University of MissouriKevin C. Dellsperger - University of Missouri
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.294(6), pp.H2659-H2668
- Publisher
- Amer Physiological Soc
- DOI
- 10.1152/ajpheart.00953.2007
- PMID
- 18424632
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Number of pages
- 10
- Grant note
- R01HL073101 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01 HL-73101-01A1 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 06/01/2008
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359950002771
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