AT1 receptor antagonism ameliorates acute pancreatitis-associated pulmonary injury

Chan, Yuk Cheung; Leung, Po Sing

doi:10.1016/j.regpep.2005.12.001

Cited by 21 publications

(16 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For morphological study, the sections were stained with hematoxylin and eosin, and they were evaluated by observers who were blind to the identity of the sections. The degree of pancreatic injury is related to the enlargement of interlobular space (i.e., the degree of edema) and destruction of the histoarchitecture of all or part of acini as described previously in our laboratory (Chan and Leung, 2006). For immunofluorescent staining, the slides were incubated with mouse anti-nitrotyrosine (1:100; Zymax, South San Francisco, CA), rabbit anti-p22 or antip67 (1:100; Santa Cruz Biotechnology, Inc.), together with goat…”

Section: Methodsmentioning

confidence: 99%

“…Plasma ␣-amylase, pancreatic myeloperoxidase (MPO) activity, and glutathione (GSH) levels were assessed using a previously described method Chan and Leung, 2006). Serum interleukin (IL)-6 and IL-1 were determined using commercially available enzyme-linked immunosorbent assay kits (BioSource International, Camarillo, CA).…”

Section: Role Of Angiotensin II In Obstructive Apmentioning

confidence: 99%

“…Treatment with RAS blockers could ameliorate pancreatic oxidative stress and histological deterioration observed in experimental AP Tsang et al, 2003). A specific antagonist for the AT 1 receptor, 2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl) benzyl] imidazole-5-methanol monopotassium salt (C 22 H 23 ClN 6 O) (losartan), has been shown to protect against AP and its associated pulmonary injury (Tsang et al, 2004b;Chan and Leung, 2006). Of great interest in this context is the evidence that AT 1 receptor antagonism decreases oxidative stress by reducing NADPH oxidase (Tsang et al, 2004b), which is a major source of reactive oxygen species (ROS).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Angiotensin II Type 1 Receptor-Dependent Nuclear Factor-κB Activation-Mediated Proinflammatory Actions in a Rat Model of Obstructive Acute Pancreatitis

Chan¹,

Leung²

2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Angiotensin II is a key mediator of inflammation, and nuclear factor-B (NF-B) plays a critical role in various inflammatory diseases, including acute pancreatitis (AP). This study sought to elucidate the mechanism mediating angiotensin II involvement in angiotensin II type 1 (AT 1 ) receptor-mediated NF-B activation, and ultimately in proinflammatory actions of AP pathogenesis. A rat model of obstructive pancreatitis was induced by ligation of the common biliopancreatic duct. Pancreatic injury was determined by assessing pancreatic histology, myeloperoxidase activity, and serum interleukin-6. Protein levels of pancreatic angiotensinogen and AT 1 receptor as well as NF-B inhibitory subunits (IB␣ and IB␤) and phospho-NF-B p65, B-related proteins (intercellular adhesion molecule-1, cyclooxygenas-2, and interleukin-1), and NADPH oxidase isoforms p67 and p22 were examined by Western blot. Nuclear B binding activity and degree of oxidative stress were determined by electrophoretic mobility shift assay and glutathione/nitrotyrosine examination, respectively. The effects of losartan, an AT 1 receptor antagonist, on NF-B-mediated proinflammatory actions were also assessed. Induction of AP was associated with a time-dependent increase in pancreatic angiotensinogen levels. AT 1 receptor blockade with losartan improved the pancreatic histological damage, myeloperoxidase activity, and serum interleukin-6. Losartan treatment also reduced AP-associated depletion of IB␤ and elevation of phospho-NF-B p65 protein expression as well as the enhanced nuclear B binding activity and elevated levels of B-related proteins. In addition, losartan treatment suppressed pancreatic glutathione and nitrotyrosine levels, which were consistent with decreased NADPH oxidase expression. These data provide substantial evidence that angiotensin II is involved in AT 1 receptor-mediated NADPH oxidase-dependent NF-B activation; thus, it might ultimately promote proinflammatory actions during AP pathogenesis.Acute pancreatitis (AP) is a pathological state with various degrees of severity, ranging from edematous AP to hemorrhagic necrotic AP. The mortality rate, which approaches 20%, is closely associated with systemic complications, manifesting as acute respiratory distress syndrome and multiple organ dysfunction syndromes. An approximate 80% of cases can be etiologically determined, whereas 20% are considered idiopathic (UK Working Party on Acute Pancreatitis, 2005). Accumulating data suggest that the renin-angiotensin system (RAS) plays an important role in AP pathogenesis. During caerulein-induced pancreatitis, major components of a local pancreatic RAS were markedly up-regulated (Tsang et al., 2004a). Treatment with RAS blockers could ameliorate pancreatic oxidative stress and histological deterioration observed in experimental AP Tsang et al., 2003). A specific antagonist for the AT 1 receptor, 2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl) benzyl] imidazole-5-methanol monopotassium salt (C 22 H 23 ClN 6 O) (losartan), has been shown to pr...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Role Of Angiotensin II In Obstructive Apmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Angiotensin II Type 1 Receptor-Dependent Nuclear Factor-κB Activation-Mediated Proinflammatory Actions in a Rat Model of Obstructive Acute Pancreatitis

Chan¹,

Leung²

2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…at ASPET Journals on May 12, 2018 jpet.aspetjournals.org atic inflammation (Ip et al, 2003a;Tsang et al, 2003Tsang et al, , 2004bChan and Leung, 2006). Prevalent therapy for pancreatitis targeting IL-6 includes neutralizing antibodies against IL-6 itself and the IL-6 receptor (Gentiletti and Fava, 2003).…”

Section: Redox-sensitive Erk-induced Pancreatic Inflammation 453mentioning

confidence: 99%

“…The specific antagonist of the AT 1 receptor, losartan, also ameliorated the pancreatic injury initiated by hyperstimulation with caerulein (Tsang et al, 2004b). The protective effects of losartan are not only restricted to local pancreatic levels but also extended to AP-induced systemic inflammation (Chan and Leung, 2006 5,6,7-tetrahydro-1H-imidazo(4,5-c)pyridine-6-carboxylic acid; PBS, phosphate-buffered saline; PD98059, 2Ј-amino-3Ј-methoxyflavone; DHE, dihydro-␤-erythroidine; CBPD, common biliopancreatic duct; CREB, cAMP-responsive element binding protein; DAPI, 4,6-diamidino-2-phenylindole; PCR, polymerase chain reaction.…”

mentioning

confidence: 91%

Involvement of Redox-Sensitive Extracellular-Regulated Kinases in Angiotensin II-Induced Interleukin-6 Expression in Pancreatic Acinar Cells

Chan

Leung²

2009

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Angiotensin II has been shown to play a role in the pathogenesis of acute pancreatitis (AP). The present investigation aimed at elucidating redox-sensitive mechanistic pathway involved in proinflammatory actions of angiotensin II during an episode of AP; in particular, the regulation of expression of cytokine interleukin (IL)-6. Exogenous angiotensin II induced IL-6 expression, activation of extracellular-regulated kinase (ERK) 1/2, and superoxide generation in pancreatic acinar cell line AR42J, which were reversed by the angiotensin II type 1 (AT 1 ) receptor antagonist, losartan (2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl) benzyl] imidazole-5-methanol monopotassium salt, C 22 H 23 ClN 6 O). Pharmacological blockade of ERK1/2 improved angiotensin II-induced IL-6 expression. Moreover, angiotensin II-induced ERK1/2 activation was suppressed by antioxidant, indicating that redox-regulated ERK1/2 mediates the cytokine expression. cAMP-responsive element-binding protein (CREB) might be involved in ERK1/2-induced IL-6 expression because phosphorylation of CREB was observed after angiotensin II treatment, which was reversed by losartan and the ERK1/2 inhibitor. These results were in close agreement with the in vivo findings using an obstructive model of AP. Obstruction of the common biliopancreatic duct time-dependently enhanced angiotensinogen levels, which correlated well with superoxide generation, ERK1/2 and CREB phosphorylation, and subsequent IL-6 expression. It is more important that changes in these parameters were antagonized by prophylactic administration of losartan. These in vitro and in vivo results indicate that angiotensin II induces redox-regulated ERK1/2 and CREB activation, thus leading to IL-6 expression in an AT 1 receptormediated manner in pancreatic acinar cells during the pathogenesis of AP.

show abstract

Current Research of the RAS in Pancreatitis and Pancreatic Cancer

Leung

2010

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

AT1 receptor antagonism ameliorates acute pancreatitis-associated pulmonary injury

Cited by 21 publications

References 45 publications

Angiotensin II Type 1 Receptor-Dependent Nuclear Factor-κB Activation-Mediated Proinflammatory Actions in a Rat Model of Obstructive Acute Pancreatitis

Angiotensin II Type 1 Receptor-Dependent Nuclear Factor-κB Activation-Mediated Proinflammatory Actions in a Rat Model of Obstructive Acute Pancreatitis

Involvement of Redox-Sensitive Extracellular-Regulated Kinases in Angiotensin II-Induced Interleukin-6 Expression in Pancreatic Acinar Cells

Current Research of the RAS in Pancreatitis and Pancreatic Cancer

Contact Info

Product

Resources

About