title: Oxidative stress causes imbalance of renal renin angiotensin system (RAS) components and hypertension in obese Zucker rats.
abstract: BACKGROUND
  Oxidative stress plays an important role in the pathogenesis of hypertension, especially in obesity-related hypertension. The natriuretic and antinatriuretic components of the renal renin angiotensin system (RAS) maintain sodium homeostasis and blood pressure. Here, we test the hypothesis that increased oxidative stress leads to the imbalance of RAS components and hypertension in obese Zucker rats.
  
  
  RESULTS
  Lean and obese rats received vehicle or tempol, a superoxide dismutase mimetic in the drinking water for 4 weeks. Compared with vehicle-treated lean rats, vehicle-treated obese rats exhibited higher blood pressure and increased renal oxidative stress, accompanied by increased diuretic and natriuretic responses to AT1R antagonist (Candesartan) and AT2R agonist (CGP-42112A) and reduced diuretic and natriuretic response to MasR agonist (Ang-[1 to 7]). Moreover, obese rats had higher ACE, AT1R and AT2R, lower ACE2 and MasR expressions in the kidney. All of the above-mentioned abnormalities were reversed to some degree by tempol treatment. In primary cultures of renal proximal tubular (RPT) cells from lean and obese rats, tempol treatment also increased AT2R, ACE2, and MasR expressions but decreased AT1R and ACE expressions in obese rats.
  
  
  CONCLUSIONS
  Taken together, our study indicated that the imbalance of renal RAS components was associated with increased oxidative stress in obese rats. Furthermore, antioxidant treatment with tempol reversed the imbalance of renal RAS components and led to diuresis and natriuresis, which, at least in part, explains the blood pressure-lowering effect of antioxidant supplementation in obesity-related hypertension.
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China (H.L., X.W., C.C., J.W., X.Z., C.L., Z.X., X.Y., W.S., C.Z.).
authors: Hao
authors: H
authors: Luo
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China (H.L., X.W., C.C., J.W., X.Z., C.L., Z.X., X.Y., W.S., C.Z.).
authors: Xinquan
authors: X
authors: Wang
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China (H.L., X.W., C.C., J.W., X.Z., C.L., Z.X., X.Y., W.S., C.Z.).
authors: Caiyu
authors: C
authors: Chen
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China (H.L., X.W., C.C., J.W., X.Z., C.L., Z.X., X.Y., W.S., C.Z.).
authors: Jialiang
authors: J
authors: Wang
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China (H.L., X.W., C.C., J.W., X.Z., C.L., Z.X., X.Y., W.S., C.Z.).
authors: Xue
authors: X
authors: Zou
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China (H.L., X.W., C.C., J.W., X.Z., C.L., Z.X., X.Y., W.S., C.Z.).
authors: Chuanwei
authors: C
authors: Li
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China (H.L., X.W., C.C., J.W., X.Z., C.L., Z.X., X.Y., W.S., C.Z.).
authors: Zaicheng
authors: Z
authors: Xu
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China (H.L., X.W., C.C., J.W., X.Z., C.L., Z.X., X.Y., W.S., C.Z.).
authors: Xiaoli
authors: X
authors: Yang
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China (H.L., X.W., C.C., J.W., X.Z., C.L., Z.X., X.Y., W.S., C.Z.).
authors: Weibin
authors: W
authors: Shi
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing, China (H.L., X.W., C.C., J.W., X.Z., C.L., Z.X., X.Y., W.S., C.Z.).
authors: Chunyu
authors: C
authors: Zeng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004326:Drinking; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009765:Obesity / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D018384:Oxidative Stress; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013113:Spin Labels; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: C524087:Agtrap protein, rat; D000975:Antioxidants; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D003497:Cyclic N-Oxides; D009842:Oligopeptides; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D043562:Receptors, G-Protein-Coupled; D013113:Spin Labels; D013777:Tetrazoles; C060894:CGP 42112A; D007703:Peptidyl-Dipeptidase A; C081643:candesartan; C001803:tempol
keywords: hypertension; obesity; oxidative stress; renin‐angiotensin system; tempol