Angiotensin-converting enzyme inhibitor attenuates pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori rats.
BACKGROUND & AIMS: 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.[1]References
- Angiotensin-converting enzyme inhibitor attenuates pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori rats. Kuno, A., Yamada, T., Masuda, K., Ogawa, K., Sogawa, M., Nakamura, S., Nakazawa, T., Ohara, H., Nomura, T., Joh, T., Shirai, T., Itoh, M. Gastroenterology (2003) [Pubmed]
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