J Korean Soc Hypertens.  2012 Sep;18(3):126-135.

Redox Regulating Protein APE1/Ref-1 Expression is Increased in Abdominal Aortic Coarctation-induced Hypertension Rats

• Song SH
• Cho EJ
• Park MS
• Lee YR
• Joo HK
• Kang G
• Kang SK
• Choi S
• Jeon BH

Abstract

BACKGROUND
Aim of study is designed to investigate whether apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) expression is changed in abdominal aortic coarctation models.
METHODS
Male Sprague-Dawley rats were randomly assigned with abdominal aortic coarctation, repaired group, sham, and control groups. Endothelial function was assessed with endothelium-dependent relaxations. Detection of superoxide anion and lipid peroxidation was performed by lucigenin chemiluminescence and thiobarbituric acid-reactive substances assay. APE1/Ref-1 expression was measured with Western blot and immunohistochemistry.
RESULTS
In anesthetized condition, the abdominal aortic coarctation rats showed hypertension as systolic/diastolic arterial pressure of 171/114 mm Hg, compared with 114/94 mm Hg of control. Endothelium-dependent relaxations were significantly impaired in the aortic coarctation which was recovered in 1 week after coarctation repair. Superoxide production and lipid peroxidation were elevated in aortic coarctation rats. In immunohistochemistry, APE1/Ref-1 expressions were increased at aorta and kidney in aortic coarctation rats. Increased APE1/Ref-1 expression in aorta was recovered by repair of coarctation.
CONCLUSIONS
Taken together, it suggests that APE1/Ref-1 expression was increased in aortic coarctation-induced hypertensive rats, suggesting a biomarker for hypertension. Impaired endothelium dependent relaxation in the aortic coarctation can be modulated by repair of coarctation or the modulation of blood pressure.

Keyword

Hypertension; Aortic coarctation; Kidney; Endothelium; Oxidative stress

MeSH Terms

Acridines
Animals
Aorta
Aortic Coarctation
Arterial Pressure
Blood Pressure
Blotting, Western
Endothelium
Humans
Hypertension
Immunohistochemistry
Kidney
Lipid Peroxidation
Luminescence
Male
Oxidation-Reduction
Oxidative Stress
Rats
Rats, Sprague-Dawley
Relaxation
Salicylamides
Superoxides
Acridines
Salicylamides
Superoxides

Figure

• 

  Fig. 1 Endothelium-dependent relaxations in the abdominal aortic coarctation rats. (A) Endothelium-dependent relaxation by acetylcholine in the abdominal aortic coarctation rats. Endothelium-dependent relaxation in the aortic rings was evoked by the treatment of acetylcholine at the range of 1 nM to 10 mM. Relaxations are expressed as a relaxation percentage of the precontracted tension obtained by phenylephrine. Each value is mean ± SEM (No. 6-9). Endothelium-dependent relaxation induced by acetylcholine was impaired in the aortic segments of aortic coarctation (AC) compared with sham controls. Repair group of aortic coarctation (ACR). p < 0.05 vs. AC. Each data showed mean ± SEM (No. 5-6). (B) Correlation between mean arterial blood pressure (MAP) and endothelium-dependent relaxations in rats. Correlation coefficient was calculated with Prism ver. 4.0 (GraphPad software, San Diego, CA, USA).

• 

  Fig. 2 Lipid peroxidation and superoxide production in the plasma of the abdominal aortic coarctation rats. (A) Lipid peroxidation in the plasma of the abdominal aortic coarctation rats. Lipid peroxidation of plasma that was obtained in each groups were determined by thiobarbituric acid-reactive substances (TBARS) assay as described in Methods. Each data showed mean ± SEM (No. 5-6). (B) Superoxide production in aorta of the abdominal aortic coarctation rats. Superoxide production was determined by lucigenin chemiluminescence assay as described in Methods. Each data showed mean ± SEM (No. 5-6). Basal and nicotinamide adenine dinucleotide phosphate (NADPH)-driven superoxide were measured in aorta of rats. NADPH (0.1 mM) was added to measure NADPH oxidase activity. CON, control; Sham, sham-operated group; AC, aortic coarctation; ACR, repair group of aortic coarctation. *p < 0.05 vs. Sham. †p < 0.05 vs. AC.

• 

  Fig. 3 Immunohistochemistry of apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) in kidney and aorta of coarctation rats. APE1/Ref-1 expression was increased in aortic coarctation groups (×400). Sham, sham-operated group; AC, aortic coarctation; ACR, repair group of aortic coarctation.

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  Fig. 4 Western blot analysis for apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) in the aorta (A, C) and kidney (B, D) of coarctation rats. Con, control; Sham, sham-operated group; AC, aortic coarctation; ACR, repair group of aortic coarctation. Each bar showed mean ± SEM (n = 4). *p < 0.05 vs. Sham. †p < 0.05 vs. AC.

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