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

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.

Keywords: ICAM-1; MDA; P-selectin; Renin-angiotensin System; Severe acute pancreatitis.

Fig. 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.

Fig. 2. Western blot analysis of the expression levels of Ang II, AT1 receptor and ICAM-1. Each bar represents the mean±SD from three samples (^*p<0.05 vs. control).

Fig. 3. P-selectin expression on platelets in three experimental groups by using flow cytometric analysis. The values represent the percentages of P-selectin positive cells.