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

Sep 29, 2026

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Portal hypertension develops with the progression of liver cirrhosis, and natriuretic peptides can lower portal pressure while simultaneously activating the renin-angiotensin-aldosterone system (RAAS). Angiotensin receptor-neprilysin inhibitors (ARNIs) may enhance natriuretic peptides and mitigate RAAS-related adverse effects. This study tested an ARNI in rats with both liver cirrhosis and portal hypertension.

LanguageEnglish

CategoryHealthcare

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Pages9

Reading Time23 min

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Abstract

Background

Methods

Results

Conclusion

Introduction

J Chin MedAssoc Original article Dual angiotensin receptor and neprilysin inhibitor reduced portal pressure through peripheral vasodilatation and decreasing systemic arterial pressure in cirrhotic rats Chon Kit Puna,b, Ching-Chih Changa,c, Chiao-Lin Chuanga,d, Hui-Chun Huanga,b,* , Shao-Jung Hsua,b,* , Yi-Hsiang Huanga,b, Ming-Chih Houa,b, Fa-Yauh Leea,b aFaculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC; bDivision of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; cDivision of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; dDivision of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC 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. Shamoperated 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. Keywords: Angiogenesis; Angiotensin receptor-neprilysin inhibitor; Liver cirrhosis; Natriuretic peptide; Portal hypertension; Renin-angiotensin-aldosterone system 1. INTRODUCTION Portal hypertension develops along with liver cirrhosis and results in lethal complications. The severity of portal hypertension has been shown to correlate with the prognosis of cirrhotic patients, and a *Address correspondence. Dr. Hui-Chun Huang and Dr. Shao-Jung Hsu, Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shi-Pai Road, Taipei 112, Taiwan, ROC. E-mail [address: hchuang2@vghtpe.gov.tw](address: hchuang2@vghtpe.gov.tw) (H.-C. Huang); [sjhsu@vghtpe.gov.tw](sjhsu@vghtpe.gov.tw) (S.-J. Hsu). Conflicts of interest: Dr. Yi-Hsiang Huang, Dr. Ming-Chih Hou and Dr. Fa-Yauh Lee, editorial board members at Journal of the Chinese Medical Association, have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article. Journal of Chinese Medical Association. (2023) 86: 786-794. Received February 9, 2023; accepted May 19, 2023. doi: 10. 1097/JCMA.0000000000000959. Copyri

FAQs

What problem does the study address in cirrhotic patients and rats?

The study addresses portal hypertension that progresses with liver cirrhosis and relates severity to poor outcomes, focusing on how to lower portal pressure without worsening systemic hemodynamics.

How were the animal models and treatment groups designed?

Male Sprague-Dawley rats received common bile duct ligation to induce cirrhosis and portal hypertension, with sham-operated rats as surgical controls. Rats were randomized to vehicle, LCZ696 (an ARNI), or valsartan for 4 weeks.

What were the main findings about portal pressure and systemic circulation?

Both LCZ696 and valsartan reduced portal hypertension and systemic arterial pressure, with the decrease in portal pressure strongly associated with lowered arterial pressure and systemic vascular resistance.

Are there cautions for ARNI use in liver cirrhosis?

The conclusion indicates caution, noting that while ARNI lowered portal pressure via peripheral vasodilatation and reduced systemic arterial pressure, there may be concerns when used in liver cirrhosis.

Sep 29, 2026

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