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Published on: October 26, 2020

Candesartan Cilexetil Restores Renal Endothelial Function Through Modulation of the ADMA-DDAH-eNOS Pathway in

Balasubramaniyan Vairappan1, Ravikumar T S2, Sundhar Mohandas1

  • 1Liver Diseases Research Lab, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India.

Journal of Clinical and Experimental Hepatology
|July 13, 2026
PubMed

Insights

CC treatment improved kidney function in cirrhotic rats by restoring nitric oxide (NO) levels and enhancing endothelial function. This suggests targeting the DDAH-1 pathway may be a promising therapy for renal dysfunction in cirrhosis.

Area of Science:

  • Nephrology
  • Hepatology
  • Pharmacology

Background:

  • Renal dysfunction is a severe complication of advanced cirrhosis and acute-on-chronic liver failure (ACLF), leading to high mortality.
  • The asymmetric dimethylarginine (ADMA)-dimethylarginine dimethylaminohydrolase (DDAH)-endothelial nitric oxide synthase (eNOS) axis plays a critical role in renal function during cirrhosis.

Purpose of the Study:

  • To investigate the role of the renal ADMA-DDAH-eNOS pathway in cirrhosis with renal dysfunction.
  • To evaluate the therapeutic effects of Compound C (CC) on this pathway in a rat model of cirrhosis and ACLF.

Main Methods:

  • Cirrhosis and renal dysfunction were induced in Wistar rats using carbon tetrachloride (CCl4).
  • Rats were treated with Compound C (CC) before an acute lipopolysaccharide (LPS) challenge to mimic ACLF.
  • Renal function, inflammatory markers, ADMA levels, DDAH-1/2 expression, and nitric oxide (NO) levels were assessed.

Main Results:

  • CCl4-induced cirrhosis led to decreased mean arterial pressure, renal blood flow, and elevated kidney injury markers and inflammation.
  • CC treatment reduced renal injury and inflammation, lowered ADMA levels, and increased phosphorylated eNOS and DDAH-1 expression.
  • CC restored renal NO levels, enhanced antioxidant activity, and reduced oxidative stress in cirrhotic rats with renal dysfunction.

Conclusions:

  • CC enhances renal NO bioavailability by upregulating DDAH-1 and eNOS, and reducing ADMA, thereby improving renal endothelial function in cirrhosis.
  • Targeting DDAH-1-mediated NO restoration offers a potential therapeutic strategy for managing renal dysfunction in cirrhosis.
Abstract

Keywords:
ADMADDAHcandesartan cilexetilcirrhosisendothelial dysfunction and renal dysfunction

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