title: Inhibition of inducible nitric oxide synthesis ameliorates liver ischemia and reperfusion injury induced transient increase in arterial stiffness.
abstract: OBJECTIVE
  Hemodynamic instability is a frequent scenario after reperfusion of ischemic liver due to major liver resection and liver transplantation. Previously, we showed that liver ischemia/reperfusion (I/R) injury induced increases in reactive oxygen/nitrogen species and inducible nitric oxide synthase (iNOS) expression impaired cardiac contractility. In addition, nitric oxide (NO) generated via iNOS may have impacts on large arterial smooth muscle tone, causing transient changes in arterial stiffness and ventricular afterload. In this study, we aim to investigate associations between iNOS and transient alternation in arterial stiffness during liver I/R injury, and effects of treatments with 1,400W, a selective iNOS inhibitor, and L-NG nitroarginine methyl ester (L-NAME), a non-specific NOS inhibitor.
  
  
  METHODS
  The arterial stiffness is evaluated using the pulse wave velocity (PWV(2)), measured by finding the means of two high-fidelity micromanometers positioned at the aortic root and left femoral artery. Liver ischemia was conducted by occluding both the hepatic artery and portal vein for 30 minutes, followed by 120 minutes of reperfusion. Studies were performed on male Sprague-Dawley rats in four groups: a sham-operated group, a liver I/R group, and those groups pretreated with 1,400W (N-[3-(aminomethyl)benzyl]acetamidine) or L-NAME. Serum NO metabolites, tumor necrosis factor-α (TNF-α) and methylguanidine (MG) were measured at baseline, 30 minutes of ischemia, and 120 minutes of reperfusion.
  
  
  RESULTS
  Post-reperfusion arterial stiffness increased by ∼14% as compared with the baseline, along with increases in serum NO metabolites, TNF-α, and MG level (P < .05); 1,400W and L-NAME treatment reduces post-reperfusion arterial stiffness by ∼5% similarly. Treatments with 1,400W and L-NAME both attenuated I/R induced increases in serum TNF-α, MG, and NO metabolites level (P < .05).
  
  
  CONCLUSIONS
  I/R-induced arterial stiffening was strongly associated with increased systemic inflammation. Comparable effects with treatments of 1,400W and L-NAME suggested that iNOS plays a dominant role in I/R-induced transient arterial stiffening.
authors.affiliation: Division of Cardiovascular Surgery, Cathay General Hospital, Taipei, Taiwan.
authors.forename: T-H
authors.initials: TH
authors.lastname: Chen
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: F-T
authors.initials: FT
authors.lastname: Liao
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Yang
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: 078625@mail.fju.edu.tw.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D063177:Pulse Wave Analysis; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D000578:Amidines; D001596:Benzylamines; D015415:Biomarkers; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester