Abstract
To clarify the role of nitric oxide (NO) in the development and progression of acute pancreatitis, we investigated the effect of various NO synthase (NOS) inhibitors and NO donors on experimental pancreatitis in rats. Closed duodenal loop (CDL)-induced pancreatitis was produced in male Wistar rats, and the animals were treated with normal saline, the NOS substrate L-arginine, the NO donor S-nitroso-N-acetylpenicillamine, aminoguanidine [which is a more powerful inhibitor of inducible NOS (iNOS) than endothelial NO synthase (eNOS)], and N-nitro-L-arginine methyl ester (L-NAME), a more powerful inhibitor of eNOS than of iNOS. All drugs were infused intravenously during a period of 12 h in each group. Pancreatic tissue was removed 12 h after creating the CDL. L-Arginine, S-nitroso-N-acetyl-penicillamine, and aminoguanidine treatment had no effect on the elevation of serum pancreatic enzymes, whereas L-NAME administration significantly exacerbated their elevation. Pathologically, L-NAME treatment resulted in a significantly worse histological score at 12 h, especially in terms of the degree of hemorrhage, acinar cell necrosis, and microvascular thrombosis. Addition of L-arginine clearly reversed the effect of L-NAME. Neither the NO substrate nor NO donor could inhibit the progression of hemorrhagic pancreatitis in CDL-induced pancreatitis. Aminoguanidine had no effect on the severity of the pancreatitis. We therefore concluded that NO production by eNOS may play a significant role in preventing the development and progression of acute pancreatitis.
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© 2001 Springer Japan
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Nishino, T., Watanabe, SI., Oyama, H., Fukuya, Y., Hayashi, N., Kobayashi, M. (2001). Role of Nitric Oxide in the Progression of Acute Pancreatitis. In: Asakura, H., Aoyagi, Y., Nakazawa, S. (eds) Trends in Gastroenterology and Hepatology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67895-3_19
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DOI: https://doi.org/10.1007/978-4-431-67895-3_19
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-67993-6
Online ISBN: 978-4-431-67895-3
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