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

Previous studies have provided evidence that several key elements of renin- angiotensin system (RAS) are present in the rat pancreas, notably angiotens inogen, 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 . Tn 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 pa ncreas. Results from western blot and semi-quantitative reverse-transcripti on polymerase chain reaction (RT-PCR) analyses unequivocally showed that ch ronic hypoxia caused a marked increase in angiotensinogen both at the prote in and gene levels when compared with that in the normoxic pancreas. Howeve r, results from RT-PCR showed that there was a differential effect of chron ic hypoxia on the expression of AT(1) and AT(2) receptor subtypes, which ex hibited subtype-specific changes in gene expression. For AT(1), chronic hyp oxia 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 hyp oxia caused a marked increase in its mRNA expression. The increased express ion of RAS component genes by chronic hypoxia and its significance of chang es may be important for physiological and pathophysiological aspects of the pancreas. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.