The role of central AT₁ receptors in age related changes of hypothalamic redox signaling and adrenomedullary tyrosine hydroxylase expression

Abstract

The aim of this study was to test the role of angiotensin II (AngII)‐mediated mechanisms in age‐related changes of hypothalamic catecholamine biosynthesis, redox signaling and sympathetic nervous system (SNS) activation. Young (5 mo, n=6) and old (27 mo, n=6) F‐344xBN rats were infused intacerebroventricularly with either artificial CSF or losartan (15 µg/hour) for 3 days using osmotic minipumps. Level of hypothalamic tyrosine hydroxylase (TH), the rate limiting enzyme in catecholamine biosynthesis, decreased significantly with age, and in response to losartan both in young and old animals. In addition, MnSOD, catalase and NADPH oxidase‐p47 levels were decreased in the hypothalamus with age, and also with losartan treatment in both age groups. Adrenomedullary TH, an indicator of SNS activity, increased significantly with age, but decreased after losartan infusion in both young and old rats reversing the age‐related TH upregulation. These results suggest that central AT1 receptor signaling play an important role in the regulation of hypothalamic redox signaling and SNS regulation.