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  3. A low-salt diet with candesartan administration is associated with acute kidney injury in nephritis by increasing nitric oxide

A low-salt diet with candesartan administration is associated with acute kidney injury in nephritis by increasing nitric oxide

  • Biomed Pharmacother. 2023 Mar 13;161:114484. doi: 10.1016/j.biopha.2023.114484.
Yanting Yu 1,  Ping Wang 2,  Zhiyun Ren 2,  Ying Xue 2,  Yutao Jia 3,  Weiwan Wang 2,  Mingda Liu 2,  Kueiching Pan 4,  Leijuan Xiao 5,  Daxi Ji 6,  Xiaoyan Wang 7
Affiliations

Affiliations

  • 1 Department of Nephrology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China; Department of Nephrology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China.
  • 2 The Core Laboratory, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China.
  • 3 Department of Nephrology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China.
  • 4 Department of Nursing, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China.
  • 5 Department of Nephrology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. Electronic address: Eileen.Xiao@benqmedicalcenter.com.
  • 6 Department of Nephrology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. Electronic address: Darren.Ji@benqmedicalcenter.com.
  • 7 Department of Nephrology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China; The Core Laboratory, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. Electronic address: Xiaoyan.wang@benqmedicalcenter.com.
PMID: 36921530 DOI: 10.1016/j.biopha.2023.114484
Abstract

A low-salt diet may activate the renin-angiotensin-aldosterone system (RAAS) and is often applied simultaneously with RAAS inhibitors, especially for treatment of proteinuric nephritis. To explore the effect of a low-salt diet combined with Angiotensin Receptor blockers (ARB) on kidney function, the proteinuric nephritis model was induced by single intravenous injection of doxorubicin, and then the SD rats were administrated with candesartan intraperitoneal injection and fed with different salt diets. Rats with low-salt plus candesartan, not either alone, experienced acute kidney injury (AKI) at day 7 and could not self-restore when extending the experiment time from 7 days to 21 days, unless switching low-salt to normal-salt. Among three nitric oxide synthetases (NOS), endothelial NOS (eNOS) was obviously elevated and PI3K-Akt-eNOS signal pathway was activated. NG-Nitro-L-Arginine Methyl Ester (L-NAME), an eNOS Inhibitor, reversed the decreased blood pressure and recovered the kidney dysfunction induced by low-salt with candesartan. The increased TUNEL-positive cells, Bax/Bcl-2 and cleaved-caspase3 protein abundance was ameliorated by L-NAME in vivo. In vitro, sodium nitroprusside, a nitric oxide donor, can also increase Bax/Bcl-2 and cleaved-caspase3 protein level in HK-2 cell. Thus, low-salt diet combined with candesartan in nephritis rats led to AKI, and the mechanism involved the increase of eNOS/NO, which linked to the decrease of blood pressure and the increase of Apoptosis. This study provides practical guidance for salt intake in cases of Ras Inhibitor usage clinically.

Keywords

Acute kidney injury; Angiotensin receptor blocker; Low-salt; Nephritis; Nitric oxide.

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