Carbonyl stress induces hypertension and cardio-renal vascular injury in Dahl salt-sensitive rats

Xianguang Chen, Takefumi Mori, Qi Guo, Chunyan Hu, Yusuke Ohsaki, Yoshimi Yoneki, Wanjun Zhu, Yue Jiang, Satoshi Endo, Keisuke Nakayama, Susumu Ogawa, Masaaki Nakayama, Toshio Miyata, Sadayoshi Ito

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27 Citations (Scopus)

Abstract

One major precursor of carbonyl stress, methylglyoxal (MG), is elevated in the plasma of chronic kidney disease (CKD) patients, and this precursor contributes to the progression of vascular injury, hypertension and renal injury in diabetic nephropathy patients. This molecule induces salt-sensitive hypertension via a reactive oxygen species-mediated pathway. We examined the role of MG in the pathogenesis of hypertension and cardio-renal injury in Dahl salt-sensitive (Dahl S) rats, which is a rat model of CKD. Nine-week-old Dahl S rats were fed a 1% NaCl diet, and 1% MG was added to their drinking water for up to 12 weeks. Blood pressure and cardio-renal injuries were compared with rats treated with tap water alone. The angiotensin II receptor blocker (ARB), candesartan (10 mg kg -1 day -1), was administered to MG Dahl S rats to determine the impact of this drug on the pathogenesis of MG-induced CKD. A progressive increase in systolic blood pressure was observed (123±1-148±5 mm Hg) after 12 weeks of MG administration. MG administration significantly increased urinary albumin excretion, glomerular sclerosis, tubular injury, myocardial collagen content and cardiac perivascular fibrosis. MG also enhanced the renal expression of Nε-carboxyethyl-lysine (an advanced glycation end product), 8-hydroxydeoxyguanosine (a marker of oxidative stress), macrophage (ED-1) positive cells (a marker of inflammation) and nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase activity. Candesartan treatment for 4 weeks significantly reduced these parameters. These results suggest that MG-induced hypertension and cardio-renal injury and increased inflammation and carbonyl and oxidative stress, which were partially preventable by an ARB.

Original languageEnglish
Pages (from-to)361-367
Number of pages7
JournalHypertension Research
Volume36
Issue number4
DOIs
Publication statusPublished - 2013 Apr 1

Keywords

  • carbonyl stress
  • chronic kidney disease
  • methylglyoxal
  • salt sensitivity

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Chen, X., Mori, T., Guo, Q., Hu, C., Ohsaki, Y., Yoneki, Y., Zhu, W., Jiang, Y., Endo, S., Nakayama, K., Ogawa, S., Nakayama, M., Miyata, T., & Ito, S. (2013). Carbonyl stress induces hypertension and cardio-renal vascular injury in Dahl salt-sensitive rats. Hypertension Research, 36(4), 361-367. https://doi.org/10.1038/hr.2012.204