Dual angiotensin receptor and neprilysin inhibitor reduced portal pressure through peripheral vasodilatation and decreasing systemic arterial pressure in cirrhotic rats

Chon Kit Pun, Ching Chih Chang, Chiao Lin Chuang, Hui Chun Huang*, Shao Jung Hsu*, Yi Hsiang Huang, Ming Chih Hou, Fa Yauh Lee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Portal hypertension develops along with the progression of liver cirrhosis. Natriuretic peptides have been shown to reduce portal pressure but concomitantly activate the renin-angiotensin-aldosterone system (RAAS). Angiotensin receptor-neprilysin inhibitors (ARNIs) upregulate natriuretic peptides and avoid the adverse effects of RAAS activation. ARNIs have been shown to reduce portal pressure in rats with pre-hepatic portal hypertension, which involves relatively little liver injury. This study aimed to evaluate the relevant effects of an ARNI in rats with both liver cirrhosis and portal hypertension. Methods: Male Sprague-Dawley rats received common bile duct ligation to induce liver cirrhosis and portal hypertension. Sham-operated rats served as surgical controls. All rats were randomly allocated into three groups to receive distilled water (vehicle), LCZ696 (an ARNI), or valsartan for 4 weeks. Portal hypertension and relevant derangements were assessed after treatment. Results: Portal hypertension and hyperdynamic circulation developed in the cirrhotic rats. In the rats with cirrhosis and portal hypertension, both LCZ696 and valsartan reduced portal hypertension, mean arterial pressure, and systemic vascular resistance. The decrease in portal pressure was highly associated with the reduction in arterial pressure and systemic vascular resistance. Blood flow in hepatic, splanchnic, and portosystemic collateral systems was not altered. LCZ696 did not significantly influence liver injury or plasma cytokine levels. Liver fibrosis and splanchnic angiogenesis were not affected. Conclusion: ARNI treatment exerted portal pressure lowering effects via peripheral vasodilatation and decreasing systemic arterial pressure in the rats with liver cirrhosis and portal hypertension. Caution should be taken when using ARNIs in liver cirrhosis.

Original languageEnglish
Pages (from-to)786-794
Number of pages9
JournalJournal of the Chinese Medical Association
Volume86
Issue number9
DOIs
StatePublished - 1 Sep 2023

Keywords

  • Angiogenesis
  • Angiotensin receptor-neprilysin inhibitor
  • Liver cirrhosis
  • Natriuretic peptide
  • Portal hypertension
  • Renin-angiotensin-aldosterone system

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