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• W2083648000 abstract "Previous studies showed that a local pancreatic renin-angiotensin system (RAS) was upregulated in experimental acute pancreatitis. RAS inhibition could attenuate pancreatic inflammation and fibrosis, which casts a new light on the role of the pancreatic RAS in pancreatitis. The present study explores the prophylactic and therapeutic potentials, and possible molecular mechanism for the antagonism of angiotensin II receptors on the changes in the severity of pancreatic injury induced by acute pancreatitis. Experimental pancreatitis was induced by an intraperitoneal injection of supra-maximal dose of cerulein. The differential effects of angiotensin II receptors inhibitors losartan and PD123319 on the pancreatic injury were assessed by virtue of using the pancreatic water content, biochemical and histological analyses. Blockade of the AT1 receptor by losartan at a dose of 200 μg/kg could markedly ameliorate the pancreatic injury induced by cerulein, as evidenced by biochemical and histopathological studies. However, blockade of the AT2 receptor by PD123319 appeared not to provide any beneficial role in cerulein-induced pancreatic injury. Both prophylactic and therapeutic treatments with losartan were effective against cerulein-induced pancreatic injury. The protective action of losartan was linked to an inhibition of NAD(P)H oxidase activity, thus consequential oxidative modification of pancreatic proteins in the pancreas. Inhibition of the AT1 receptor, but not AT2 receptor, may play a beneficial role in ameliorating the severity of acute pancreatitis. The differential effects of AT1 and AT2 inhibitors on cerulein-induced pancreatic injury might be due to the distinctive mechanism of the AT1 and AT2 receptors on the activation of NAD(P)H oxidase. Thus the protective role of AT1 receptor antagonist, losartan, could be mediated by the inhibition of NAD(P)H oxidase-dependent generation of reactive oxygen species (ROS)." @default.
• W2083648000 created "2016-06-24" @default.
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• W2083648000 date "2004-02-01" @default.
• W2083648000 modified "2023-09-27" @default.
• W2083648000 title "Prophylactic and therapeutic treatments with AT1 and AT2 receptor antagonists and their effects on changes in the severity of pancreatitis" @default.
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• W2083648000 doi "https://doi.org/10.1016/s1357-2725(03)00257-7" @default.
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