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Effects of Local Pancreatic Renin-Angiotensin System on the Microcirculation of Rat with Severe Acute Pancreatitis.

Pan Z, Feng L, Long H, Wang H, Feng J, Chen F - Korean J. Physiol. Pharmacol. (2015)

Bottom Line: Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP.The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction.The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology Surgery, The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science & Technology, Wuhan 430014, Hubei, China.

ABSTRACT
Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis.

No MeSH data available.


Related in: MedlinePlus

Histological changes in pancreatic tissue sections under the light microscopy (magnification, ×200). (A) Sham-operated group, pancreatic tissue section shows normal acinar structure. (B) SAP group, massive destruction was observed in acinar glandular structure and islet cells of pancreatic tissue. (C) SAP plus valsartan treatment group, relative preservation in pancreatic structure is seen compared with the SAP group. The black arrow indicates necrotic cells, the red arrow indicates edema, and the blue arrow indicates inflammatory cell infiltrations.
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Figure 1: Histological changes in pancreatic tissue sections under the light microscopy (magnification, ×200). (A) Sham-operated group, pancreatic tissue section shows normal acinar structure. (B) SAP group, massive destruction was observed in acinar glandular structure and islet cells of pancreatic tissue. (C) SAP plus valsartan treatment group, relative preservation in pancreatic structure is seen compared with the SAP group. The black arrow indicates necrotic cells, the red arrow indicates edema, and the blue arrow indicates inflammatory cell infiltrations.

Mentions: In this study, SAP model was set up by injecting 10% DMSO solution (2 ml/kg) into femoral vein of rats. For the valsartan treatment group, injection of constant volume of 10% DMSO solution with valsartan (5 mg/kg) was also performed in rats after SAP induction for 30 min. In this model, valsartan didn't cause the mortality of SAP rats after 72 h. Therefore, further studies on the effects of valsartan on pancreatic histology were carried out. The morphology of pancreas samples were examined and compared among the treatment groups with an attempt to assess the effects of valsartan on local pancreatic injury. As shown in Fig. 1, under the light microscope, histological examination demonstrated that pancreatic tissues in SAP rats exhibited severe edema with large interstitial spaces, vascular congestion, necrosis, and inflammation (Fig. 1B). Part or all of the acini in the SAP group were showed a high degree of destruction on the histoarchitecture (Fig. 1B). Valsartan was indicated to improve the integrity and architecture of the acini (Fig. 1C). There was no significant necrosis and the degree of pancreatic tissue hyperemia, edema and inflammatory cell infiltration in these rats was reduced. In the SO group, there was no obvious histological change, based on complete pancreatic lobules and clear interstitial space observed. However, further studies are needed to clarify the changes in the pancreatic histology by using immunohistochemistry and/or some other molecular techniques in the future.


Effects of Local Pancreatic Renin-Angiotensin System on the Microcirculation of Rat with Severe Acute Pancreatitis.

Pan Z, Feng L, Long H, Wang H, Feng J, Chen F - Korean J. Physiol. Pharmacol. (2015)

Histological changes in pancreatic tissue sections under the light microscopy (magnification, ×200). (A) Sham-operated group, pancreatic tissue section shows normal acinar structure. (B) SAP group, massive destruction was observed in acinar glandular structure and islet cells of pancreatic tissue. (C) SAP plus valsartan treatment group, relative preservation in pancreatic structure is seen compared with the SAP group. The black arrow indicates necrotic cells, the red arrow indicates edema, and the blue arrow indicates inflammatory cell infiltrations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4499641&req=5

Figure 1: Histological changes in pancreatic tissue sections under the light microscopy (magnification, ×200). (A) Sham-operated group, pancreatic tissue section shows normal acinar structure. (B) SAP group, massive destruction was observed in acinar glandular structure and islet cells of pancreatic tissue. (C) SAP plus valsartan treatment group, relative preservation in pancreatic structure is seen compared with the SAP group. The black arrow indicates necrotic cells, the red arrow indicates edema, and the blue arrow indicates inflammatory cell infiltrations.
Mentions: In this study, SAP model was set up by injecting 10% DMSO solution (2 ml/kg) into femoral vein of rats. For the valsartan treatment group, injection of constant volume of 10% DMSO solution with valsartan (5 mg/kg) was also performed in rats after SAP induction for 30 min. In this model, valsartan didn't cause the mortality of SAP rats after 72 h. Therefore, further studies on the effects of valsartan on pancreatic histology were carried out. The morphology of pancreas samples were examined and compared among the treatment groups with an attempt to assess the effects of valsartan on local pancreatic injury. As shown in Fig. 1, under the light microscope, histological examination demonstrated that pancreatic tissues in SAP rats exhibited severe edema with large interstitial spaces, vascular congestion, necrosis, and inflammation (Fig. 1B). Part or all of the acini in the SAP group were showed a high degree of destruction on the histoarchitecture (Fig. 1B). Valsartan was indicated to improve the integrity and architecture of the acini (Fig. 1C). There was no significant necrosis and the degree of pancreatic tissue hyperemia, edema and inflammatory cell infiltration in these rats was reduced. In the SO group, there was no obvious histological change, based on complete pancreatic lobules and clear interstitial space observed. However, further studies are needed to clarify the changes in the pancreatic histology by using immunohistochemistry and/or some other molecular techniques in the future.

Bottom Line: Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP.The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction.The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology Surgery, The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science & Technology, Wuhan 430014, Hubei, China.

ABSTRACT
Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis.

No MeSH data available.


Related in: MedlinePlus