on July 21, 2005
Published online before print July 21, 2005, doi: 10.1161/01.ATV.0000178993.13222.f2
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Submitted on January 11, 2005
Accepted on July 11, 2005
Oxidative Stress Promotes Endothelial Cell Apoptosis and Loss of Microvessels in the Spontaneously Hypertensive Rats
Nobuhiko Kobayashi ;
From the Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, Calif.
* To whom correspondence should be addressed. E-mail: gwss{at}bioeng.ucsd.edu.
Objective--Endothelial cell apoptosis caused by oxidative stress may lead to the loss of microvessels (rarefaction) in hypertension. We examine here the effects of antioxidants on cell apoptosis and rarefaction.
Methods and Results--The juvenile spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were treated with superoxide scavengers, Tempol or Tiron, during growth. After the treatment, oxidative stress status, endothelial cell apoptosis rate, and microvessel length density in skeletal muscle and mesentery were evaluated in comparison with age-matched controls. Untreated 16-week-old SHR had higher oxidative stress (P<0.01) and cell apoptosis rate (P<0.05) and lower microvessel length density (371±17 mm/mm3 [P<0.01]) compared with age-matched WKY rats (435±15 mm/mm3). In the SHR, but not in WKY rats, systemically applied antioxidants attenuated oxidative stress and cell apoptosis rate (P<0.05 versus untreated controls) and prevented the loss of microvessels (411±15 mm/mm3 for Tempol [P<0.01 versus untreated control] and 399±17 mm/mm3 for Tiron [P<0.05]).
Conclusions--Antioxidant treatment with cell-permeable superoxide scavengers inhibits endothelial cell apoptosis and prevents microvessel rarefaction in the SHR during growth.
Key words: arterial hypertension • capillary • endothelial cell apoptosis • microvessels • oxidative stress • rarefaction • superoxide
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