Activation of local renin-angiotensin system by chronic hypoxia in rat pancreas

Abstract

Previous studies have provided evidence that several key elements of renin-angiotensin system (RAS) are present in the rat pancreas, notably angiotensinogen, which is mandatory for intracellular generation of physiologically active angiotensin II. The data support the existence of an intrinsic RAS, which may be important for pancreatic blood flow and ductal anion secretion. In the present study, the effect of chronic hypoxia on the expression of RAS components, particularly at the levels of its precursor angiotensinogen and its receptor subtypes AT(1) and AT(2), were investigated in the rat pancreas. Results from western blot and semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) analyses unequivocally showed that chronic hypoxia caused a marked increase in angiotensinogen both at the protein and gene levels when compared with that in the normoxic pancreas. However, results from RT-PCR showed that there was a differential effect of chronic hypoxia on the expression of AT(1) and AT(2) receptor subtypes, which exhibited subtype-specific changes in gene expression. For AT(1), chronic hypoxia did not cause a significant change in mRNA expression for AT(1a) but a significant increase in mRNA expression for AT(1b). For AT(2), chronic hypoxia caused a marked increase in its mRNA expression. The increased expression of RAS component genes by chronic hypoxia and its significance of changes may be important for physiological and pathophysiological aspects of the pancreas.