title: Alteration of the renin-angiotensin system in caerulein induced acute pancreatitis in the mouse.
abstract: BACKGROUND
  The objective of this study was to determine if RAS bioactive enzymes and peptides are perturbed in acute pancreatitis and associated lung injury.
  
  
  METHODS
  The intervention group of mice were treated with ten hourly intraperitoneal (i.p.) injections of caerulein (50 μg/kg) to induce acute pancreatitis. Animals were euthanized, samples of pancreas, lung and blood were collected, and plasma was prepared and stored for subsequent analysis. ACE and ACE2 activities were determined by spectrofluorometric assay. ACE, ACE2, Ang II and Ang-(1-7) levels were quantified by ELISA.
  
  
  RESULTS
  There was a significant decrease in ACE2 enzymatic activity in pancreatic and lung tissues of mice with acute pancreatitis. In contrast, there were no significant changes in measured levels of ACE and ACE2 in the pancreas, and lung or activity of ACE in pancreatic and lung tissue following acute pancreatitis. There were no significant differences in the activities and levels of circulating ACE and ACE2 following acute pancreatitis. The ACE to ACE2 activity ratio was markedly increased in pancreatic and lung tissues of mice with acute pancreatitis. No significant changes were observed in the levels of Ang II except for a decrease in lung tissue. No changes were observed in Ang-(1-7) levels in pancreas, lung and plasma between the groups. The Ang II to Ang-(1-7) ratio was increased in the pancreas but was decreased in the lung following caerulein treatment.
  
  
  CONCLUSIONS
  These data suggest dysregulation of RAS in acute pancreatitis as evidenced by altered Ang II/Ang-(1-7) levels induced by the imbalance of ACE/ACE2 activity.
authors.affiliation: Department of Pathology, University of Otago, Christchurch, New Zealand.
authors.forename: Ravinder Reddy
authors.initials: RR
authors.lastname: Gaddam
authors.affiliation: Department of Pathology, University of Otago, Christchurch, New Zealand.
authors.forename: Abel Damien
authors.initials: AD
authors.lastname: Ang
authors.affiliation: Department of Pathology, University of Otago, Christchurch, New Zealand.
authors.forename: Alireza
authors.initials: A
authors.lastname: Badiei
authors.affiliation: Department of Pathology, University of Otago, Christchurch, New Zealand.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Chambers
authors.affiliation: Department of Pathology, University of Otago, Christchurch, New Zealand. Electronic address: madhav.bhatia@otago.ac.nz.
authors.forename: Madhav
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D000803:Angiotensin I / Q000235:genetics / Q000378:metabolism; D000804:Angiotensin II / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002108:Ceruletide / Q000633:toxicity*; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010195:Pancreatitis / Q000139:chemically induced* / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011897:Random Allocation; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D000804:Angiotensin II; D002108:Ceruletide; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)
keywords: Acute pancreatitis; Angiotensin-converting enzyme; Angiotensin-converting enzyme 2; Caerulein; Inflammation; Renin-angiotensin system