Antioxidant treatment with tempol and apocynin prevents endothelial dysfunction and development of renovascular hypertension.
BACKGROUND
Two-kidney-one-clip (2K-1C) rats develop renovascular hypertension associated with endothelial dysfunction and elevated levels of oxidative stress. The role of oxidative damage is unknown in vascular dysfunction coupled with 2K-1C hypertension. The aims of this study were to evaluate the effects of chronic treatment with a superoxide dismutase (SOD) mimetic (tempol) and an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidase (apocynin) on the development of hypertension, endothelial dysfunction, and oxidative damage in 2K-1C rats.


METHODS
2K-1C rats and sham-operated rats were treated with tempol or apocynin for 40 days, while the corresponding nontreated groups received tap water. Blood pressure (BP), mesenteric arterial reactivity, plasma and mesentery oxidative damage, mesenteric protein expression, and antioxidant activities were compared among the four groups.


RESULTS
Chronic treatment with tempol (1 mmol/l) or apocynin (33 microg/kg/day) impaired the development of hypertension in 2K-1C rats and did not change the BP in control animals. The reduction in vasodilatory effect induced by acetylcholine (ACh) in the mesenteric arterial beds (MABs) of 2K-1C rats was restored by tempol and apocynin. Plasma and mesentery levels of malondialdehyde (MDA) were higher in 2K-1C rats, and these levels were significantly reduced by the administration of tempol and apocynin. Mesenteric SOD activity and expression were higher in 2K-1C rats than in the controls, and treatment with tempol resulted in a reduction in SOD activity.


CONCLUSIONS
The data suggest that a compromised mechanism of antioxidant defense and an increase in oxidative damage contribute to the development of hypertension and associated vascular dysfunction in 2K-1C rats, and that tempol and apocynin prevent these effects.
Departament of Pharmacology, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
Cristiane A
CA
Costa
Taline A S
TA
Amaral
Lenize C R M
LC
Carvalho
Dayane T
DT
Ognibene
Andréa F E
AF
da Silva
Monique B
MB
Moss
Samuel S
SS
Valença
Roberto S
RS
de Moura
Angela C
AC
Resende
D000098:Acetophenones / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism
D000098:Acetophenones; D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; C056165:acetovanillone; D002374:Catalase; D013482:Superoxide Dismutase; C001803:tempol