PMID- 34450166
OWN - NLM
STAT- MEDLINE
DCOM- 20211005
LR  - 20240226
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 284
DP  - 2021 Nov 1
TI  - DPP4 inhibitor reduces portal hypertension in cirrhotic rats by normalizing 
      arterial hypocontractility.
PG  - 119895
LID - S0024-3205(21)00882-1 [pii]
LID - 10.1016/j.lfs.2021.119895 [doi]
AB  - AIMS: Dipeptidyl peptidase-4 inhibitor (DPP4i), a new antidiabetic agent, is 
      reported to affect the progression of chronic liver diseases. The study aims to 
      investigate the effects of DPP4i on contractile response, splanchnic 
      hemodynamics, and portal pressure in cirrhotic rats. MATERIALS AND METHODS: A rat 
      model of carbon tetrachloride-induced cirrhosis was used in this study. Sixteen 
      rats with cirrhosis were treated with DDP4i sitagliptin for 5 consecutive days. 
      Portal and systemic pressures and portal blood flow were measured. Mesenteric 
      arterioles were isolated, and concentration-response curves to norepinephrine 
      (NE) were evaluated. The expression of NADPH oxidase (Nox)1, Nox2, Nox4, and 
      soluble epoxide hydrolase (sEH) were detected. Reactive oxygen species (ROS) and 
      epoxyeicosatrienoic acid (EET) levels in mesenteric arteries were also measured. 
      KEY FINDINGS: In cirrhotic rats, sitagliptin significantly reduced portal blood 
      flow and portal pressure without effects on systemic pressure and reversed the 
      decreased response of mesenteric arterioles to NE in an endothelium-dependent 
      manner. Sitagliptin suppressed the increased Nox4 expression and ROS production. 
      In vitro studies showed that Nox4 inhibitor enhanced arteriolar response to NE 
      and reduced hydrogen peroxide (H(2)O(2)) level in cirrhotic rats. Sitagliptin 
      also reduced EET levels and increased sEH expression of mesenteric vessels. 
      Pre-incubation with sEH inhibitor in vitro reversed sitagliptin-induced 
      augmentation of response to NE in cirrhotic rats. SIGNIFICANCE: DPP4 inhibition 
      by sitagliptin in vivo has beneficial effects on portal hypertension in cirrhotic 
      rats through normalizing arterial hypocontractility. DDP4 inhibitor may be a 
      novel strategy in the treatment of patients with cirrhosis and portal 
      hypertension.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Wang, Xinxin
AU  - Wang X
AD  - Department of Radiation Oncology, The Third Hospital of Nanchang, Nanchang 
      330025, China.
FAU - Gu, Haitao
AU  - Gu H
AD  - Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai 200080, China.
FAU - Li, Kaichun
AU  - Li K
AD  - Oncology Department, Shanghai Fourth People's Hospital Affiliated to Tongji 
      University School of Medicine, Shanghai 200434, China.
FAU - Lin, Jiayun
AU  - Lin J
AD  - Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao 
      Tong University School of Medicine, Shanghai 201999, China.
FAU - Zhu, Yiming
AU  - Zhu Y
AD  - Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao 
      Tong University School of Medicine, Shanghai 201999, China.
FAU - Deng, Wensheng
AU  - Deng W
AD  - Department of General Surgery, The First Affiliated Hospital of Nanchang 
      University, Nanchang 33006, China. Electronic address: wensheng.deng@shgh.cn.
LA  - eng
PT  - Journal Article
DEP - 20210824
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Arteries/drug effects/*physiopathology
MH  - Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use
MH  - Hemodynamics/drug effects
MH  - Hydrogen Peroxide/metabolism
MH  - Hypertension, Portal/*complications/*drug therapy/physiopathology
MH  - Liver/drug effects/pathology
MH  - Liver Cirrhosis/*complications/drug therapy/*physiopathology
MH  - Male
MH  - Mesenteric Arteries/drug effects/physiopathology
MH  - NADPH Oxidase 4/metabolism
MH  - Norepinephrine/pharmacology
MH  - Rats, Sprague-Dawley
MH  - Sitagliptin Phosphate/pharmacology
MH  - Up-Regulation/drug effects
MH  - *Vasoconstriction/drug effects
MH  - Rats
OTO - NOTNLM
OT  - Arterial hypocontractility
OT  - DPP4
OT  - Liver cirrhosis
OT  - Nox4
OT  - Portal hypertension
OT  - sEH
EDAT- 2021/08/28 06:00
MHDA- 2021/10/06 06:00
CRDT- 2021/08/27 20:12
PHST- 2020/10/07 00:00 [received]
PHST- 2021/08/08 00:00 [revised]
PHST- 2021/08/16 00:00 [accepted]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/10/06 06:00 [medline]
PHST- 2021/08/27 20:12 [entrez]
AID - S0024-3205(21)00882-1 [pii]
AID - 10.1016/j.lfs.2021.119895 [doi]
PST - ppublish
SO  - Life Sci. 2021 Nov 1;284:119895. doi: 10.1016/j.lfs.2021.119895. Epub 2021 Aug 
      24.