Oxidative stress promotes endothelial cell apoptosis and loss of microvessels in the spontaneously hypertensive rats.
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.


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.
Kobayashi
Nobuhiko
N
Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093-0412, USA.
DeLano
Frank A
FA
Schmid-Schönbein
Geert W
GW
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology*; D005456:Fluorescent Dyes; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D008297:Male; D008833:Microcirculation; D018482:Muscle, Skeletal / Q000098:blood supply; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010617:Phenanthridines; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013113:Spin Labels; D013152:Splanchnic Circulation
D000975:Antioxidants; D003497:Cyclic N-Oxides; D005456:Fluorescent Dyes; D010617:Phenanthridines; D013113:Spin Labels; C058428:hydroethidine; C001803:tempol