Enhanced oxidative stress and impaired thioredoxin expression in spontaneously hypertensive rats.
As oxidative stress plays a crucial role in the development and pathogenesis of hypertension, we analyzed the redox (reduction/oxidation) status in tissues from Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP). Expressions of 8-hydroxy-2'-deoxyguanosine, a marker for oxidative stress-induced DNA damage, and protein carbonylation, a marker for oxidation status of proteins, were enhanced in aorta, heart, and kidney from SHR and SHRSP compared with WKY. The expression of redox regulating protein, thioredoxin (TRX), estimated by immunohistochemistry and western blot, and expression of TRX gene estimated by real-time RT-PCR were markedly suppressed in those tissues from SHR and SHRSP compared with WKY. Induction of TRX was impaired after angiotension II treatment in peripheral blood mononuclear cells isolated from SHR and SHRSP compared with those isolated from WKY. Although previous reports have shown that TRX is induced by a variety of oxidative stress in tissues, the present study shows the impaired induction of TRX in tissues from genetically hypertensive rats despite the relative increment of oxidative stress. Redox imbalance in essential organs may play a crucial role in the development and pathogenesis of hypertension.
Tanito
Masaki
M
Nakamura
Hajime
H
Kwon
Yong-Won
YW
Teratani
Akie
A
Masutani
Hiroshi
H
Shioji
Keisuke
K
Kishimoto
Chiharu
C
Ohira
Akihiro
A
Horie
Ryoichi
R
Yodoi
Junji
J
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013879:Thioredoxins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
D000804:Angiotensin II; D013879:Thioredoxins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine