Role of the angiotensin II AT2 receptor in inflammation and oxidative stress: opposing effects in lean and obese Zucker rats

被引：58
作者：
Sabuhi, Rifat [1 ]
Ali, Quaisar [1 ]
Asghar, Mohammad [1 ]
Al-Zamily, Najah Riesh Hadi [2 ]
Hussain, Tahir [1 ]
机构：
[1] Univ Houston, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77204 USA
[2] Kufa Univ, Dept Pharmacol & Therapeut, Fac Med, Kufa, Iraq
来源：
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY | 2011年 / 300卷 / 03期
关键词：
CGP-42112A; superoxide dismutase; TNF-alpha; IL-6; NF-kappa B; nitric oxide; TYPE-2; RECEPTOR; KAPPA-B; METABOLIC SYNDROME; NATRIURESIS; DYSFUNCTION; INHIBITION; SYSTEM;
D O I：
10.1152/ajprenal.00616.2010
中图分类号：
Q4 [生理学];
学科分类号：
071003 ;
摘要：
Sabuhi R, Ali Q, Asghar M, Al-Zamily NR, Hussain T. Role of the angiotensin II AT2 receptor in inflammation and oxidative stress: opposing effects in lean and obese Zucker rats. Am J Physiol Renal Physiol 300: F700-F706, 2011. First published January 5, 2011; doi:10.1152/ajprenal.00616.2010.-Inflammation and oxidative stress are believed to contribute to hypertension in obesity/diabetes. Recently, we reported a role for the AT2 receptor in blood pressure control in obese Zucker rats. However, the role of AT2 receptors in inflammation and oxidative stress in obesity is not known. Therefore, in the present study, we tested the effects of the AT2 receptor agonist CGP-42112A on inflammation and oxidative stress in obese Zucker rats and compared them in their lean counterparts. Rats were systemically treated with either vehicle (control) or CGP-42112A (1 mu g.kg(-1).min(-1); osmotic pump) for 2 wk. Markers of inflammation (CRP, MCP-1, TNF-alpha, and IL-6) and oxidative stress (HO-1, gp-91phox) as well as an antioxidant (SOD) were determined. Control obese rats had higher plasma levels of CRP, MCP-1, TNF-alpha, IL-6, and HO-1 compared with control lean rats. Conversely, plasma SOD activity was lower in control obese than in control lean rats. Furthermore, the protein levels of TNF-alpha and gp-91phox were higher in the kidney cortex of control obese rats. Interestingly, CGP-42112A treatment in obese rats reduced the plasma and kidney cortex inflammatory (TNF-alpha, IL-6) and oxidative stress (gp-91phox) markers and increased plasma SOD activity to the levels seen in lean control rats. However, CGP-42112A treatment in lean rats increased inflammatory (TNF-alpha, IL-6) and oxidative stress (gp-91phox) markers in the plasma and kidney cortex. Our present studies suggest anti-inflammatory and antioxidative functions of AT2 receptor in obese Zucker rats but proinflammatory and prooxidative functions in lean Zucker rats.
引用
收藏
页码：F700 / F706
页数：7
相关论文
共 46 条
[1]   High glucose up-regulates angiotensin II subtype 2 receptors via interferon regulatory factor-1 in proximal tubule epithelial cells [J].
Ali, Quaisar ;
Sabuhi, Rifat ;
Hussain, Tahir .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2010, 344 (1-2) :65-71
[2]   Update on tissue renin-angiotensin systems [J].
Bader, Michael ;
Ganten, Detlev .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2008, 86 (06) :615-621
[3]  
Bokoch GM, 2009, ANTIOXID REDOX SIGN, V11, P2429, DOI 10.1089/ARS.2009.2590
[4]  
BRAY GA, 1977, FED PROC, V36, P148
[5]   Angiotensin type 2 receptor-mediated hypotension in angiotensin type-1 receptor-blocked rats [J].
Carey, RM ;
Howell, NL ;
Jin, XH ;
Siragy, HM .
HYPERTENSION, 2001, 38 (06) :1272-1277
[6]   The Effect of Chronic Candesartan Therapy on the Metabolic Profile and Renal Tissue Cytokine Levels in the Obese Zucker Rat [J].
Ecelbarger, Carolyn M. ;
Rash, Arjun ;
Sinha, Rajesh K. ;
Tiwari, Swasti .
MEDIATORS OF INFLAMMATION, 2010, 2010
[7]   Obesity is the major contributor to vascular dysfunction and inflammation in high-fat diet hypertensive rats [J].
Elmarakby, Ahmed A. ;
Imig, John D. .
CLINICAL SCIENCE, 2010, 118 (3-4) :291-301
[8]   The adipose-tissue renin-angiotensin-aldosterone system:: role in the metabolic syndrome? [J].
Engeli, S ;
Schling, P ;
Gorzelniak, K ;
Boschmann, M ;
Janke, E ;
Ailhaud, G ;
Teboul, M ;
Massiéra, F ;
Sharma, AA .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2003, 35 (06) :807-825
[9]   Much Ado about Adenosine: Adenosine Synthesis and Function in Regulatory T Cell Biology [J].
Ernst, Peter B. ;
Garrison, James C. ;
Thompson, Linda F. .
JOURNAL OF IMMUNOLOGY, 2010, 185 (04) :1993-1998
[10]   Effect of simultaneous blockade of AT1 and AT2 receptors on the NFκB pathway and renal inflammatory response [J].
Esteban, V ;
Ruperez, M ;
Vita, JR ;
López, ES ;
Mezzano, S ;
Plaza, JJ ;
Egido, J ;
Ruiz-Ortega, M .
KIDNEY INTERNATIONAL, 2003, 64 :S33-S38
12345