Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components

• Published in: Physiological genomics Vol. 43; no. 13; pp. 829 - 835
• Main Authors: Gilliam-Davis, Shea, Gallagher, Patricia E, Payne, Valerie S, Kasper, Sherry O, Tommasi, Ellen N, Westwood, Brian M, Robbins, Michael E, Chappell, Mark C, Diz, Debra I
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.07.2011
• Subjects: Age; Aging; Aging - drug effects; Aging - genetics; Angiotensin II; angiotensinogen; Angiotensinogen - genetics; Angiotensinogen - metabolism; Animals; Brain; Dual-Specificity Phosphatases - genetics; Dual-Specificity Phosphatases - metabolism; Enzymes; Food intake; Gene expression; Gene Expression Regulation - drug effects; Geriatrics; Imidazoles - pharmacology; Leptin - genetics; Leptin - metabolism; Leptin receptors; Male; Mediodorsal Thalamic Nucleus - drug effects; Mediodorsal Thalamic Nucleus - metabolism; Medulla oblongata; Neprilysin; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Rats; Rats, Inbred F344; Receptor mechanisms; Receptor, Angiotensin, Type 1 - metabolism; Regression Analysis; Renin; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal transduction; Tetrazoles - pharmacology; Time Factors
• ISSN: 1094-8341; 1531-2267
• DOI: 10.1152/physiolgenomics.00167.2010

In Fischer 344 (F344) rats, renin-angiotensin system (RAS) blockade for 1 yr with the angiotensin II type 1 (AT(1)) receptor blocker L-158,809 prevents age-related impairments in metabolic function, similar to transgenic rats with low glial angiotensinogen (Aogen). Brain RAS regulation may contribute to the benefits of long-term systemic AT(1) antagonism. We assessed the mRNA of RAS components in the dorsomedial medulla of F344 rats at 3 (young; n = 8) or 15 mo of age (old; n = 7) and in rats treated from 3 to 15 mo of age with 20 mg/l of the AT(1) receptor antagonist L-158,809 (Old+L; n = 6). Aogen and renin mRNA were lower in the young compared with old group. Angiotensin-converting enzyme (ACE) mRNA was lower in the old and Old+L compared with the young group. ACE2 and neprilysin expression were significantly higher in Old+L compared with young or old rats. AT(1b), AT(2), and Mas receptor mRNA were higher with treatment. Leptin receptor mRNA was lower in the old rats and this was prevented by L-158,809 treatment. Dual-specificity phosphatase 1 (DUSP1) mRNA was highest in the Old+L group. Aggregate correlate summation revealed a positive relationship for Mas receptor mRNA with food intake. The findings provide evidence for regulation of dorsomedial medullary renin and Aogen mRNA during aging. Long-term AT(1) receptor blockade increases the mRNA of the enzymes ACE2 and neprilysin and the MAS receptor, which could potentially shift the balance from ANG II to ANG-(1-7) and prevent age-related declines in the leptin receptor and its signaling pathway.