The effect of chronic hypoxia on the expression of renin-angiotensin system in the rat pancreas

Abstract

Previous studies have demonstrated the presence of several major renin-angiotensin system (RAS) components in the rat pancreas including the component of angiotensinogen which is indispensable for intracellular angiotensin generation. The data support the existence of a local RAS in the rat pancreas with possible functions in pancreatic blood flow and ductal anion secretion. The up-regulation of RAS components in the lung and heart and their implicated functions has been demonstrated in chronically hypoxic rats. Nothing is known about the effect of chronic hypoxia on the expression of RAS in the rat pancreas. In the present study, the regulated expression of RAS components, particularly the angiotensinogen and angiotensin II receptor subtypes, AT1a, AT1b and AT2 was investigated by immunocytochemical and molecular biological techniques. Sprague-Dawley rats were treated in isobaric hypoxia by placing in an acrylic chamber filled with 10% oxygen for 4–5 weeks while age and time matched rats as normoxic control were kept in the same housing with breathing in room air. Results from western blot analysis and reverse transcription polymerase chain reaction (RT-PCR) showed that the expression of angiotensinogen protein and its mRNA was increased with similar levels in hypoxic pancreas when compared with that in normoxic pancreas. The expression of AT1a, AT1b and AT2 was found to be consistently up-regulated in hypoxic pancreas when compared with that in normoxic pancreas. On the other hand, immunocytochemical results showed that immunoreactivity for angiotensinogen was increased and localized to the endothelium of pancreatic blood vessels and epithelium of pancreatic ducts in chronically hypoxic pancreas. The present study suggests that the expression of the pancreatic RAS is subject to chronically hypoxic regulation which may play a role in physiological and pathophysiological aspects of the pancreas.