title: Angiotensin-converting enzyme inhibitor attenuates pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori rats.
abstract: OBJECTIVE
  Pancreatic stellate cells have some similarities to hepatic stellate cells and an intrinsic renin-angiotensin system is present in the pancreas and is enhanced in acute pancreatitis and chronic pancreatic hypoxia. We assessed the effects of lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, on spontaneously occurring chronic pancreatitis.
  
  
  METHODS
  Lisinopril in drinking water (20, 50, or 200 mg/L) was administered to 10-week-old male Wistar Bonn/Kobori (WBN/Kob) rats for 10 weeks and then the inflammatory parameters, fibrosis, serum and pancreatic ACE activity, and expression of transforming growth factor-beta1 (TGF-beta1) messenger RNA (mRNA) as well as positive immunostaining for alpha-smooth muscle actin (alpha-SMA) were assessed.
  
  
  RESULTS
  Lisinopril attenuated gross alterations in the pancreas. This protective effect was confirmed quantitatively by significant increases in pancreatic weights and decreases in pancreatic myeloperoxidase (MPO) activity (an index of granulocyte infiltration), pancreatic hydroxyproline content (an index of collagen deposition), ratio of fibrous tissue, and histologic scores. Lisinopril significantly reduced serum ACE activity but it did not affect pancreatic activity. High doses of lisinopril suppressed the overexpression of TGF-beta1 mRNA measured by reverse-transcription polymerase chain reaction (RT-PCR) and decreased the number of alpha-SMA-positive cells (activated pancreatic stellate cells) in the pancreas.
  
  
  CONCLUSIONS
  Lisinopril alleviated chronic pancreatitis and fibrosis in male WBN/Kob rats. It suppressed the expression of TGF-beta1 mRNA, resulting in the prevention of pancreatic stellate cell activation, which may be involved in the observed protection. We propose that an ACE inhibitor may be useful for treating chronic pancreatitis.
authors.affiliation: First Department of Internal Medicine, Nagoya City University Medical School, Nagoya, Aichi, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuno
authors.forename: Tamaki
authors.initials: T
authors.lastname: Yamada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Masuda
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Mitsue
authors.initials: M
authors.lastname: Sogawa
authors.forename: Soichi
authors.initials: S
authors.lastname: Nakamura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ohara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nomura
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
authors.forename: Makoto
authors.initials: M
authors.lastname: Itoh
mesh_terms: D000199:Actins / Q000032:analysis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D006909:Hydroxyproline / Q000032:analysis; D007150:Immunohistochemistry; D017706:Lisinopril / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
chemical_list: D000199:Actins; D000806:Angiotensin-Converting Enzyme Inhibitors; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017706:Lisinopril; D009195:Peroxidase; D007703:Peptidyl-Dipeptidase A; D006909:Hydroxyproline