title: Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components.
abstract: 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.
authors.affiliation: The Hypertension & Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1032, USA.
authors.forename: Shea
authors.initials: S
authors.lastname: Gilliam-Davis
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Gallagher
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Payne
authors.forename: Sherry O
authors.initials: SO
authors.lastname: Kasper
authors.forename: Ellen N
authors.initials: EN
authors.lastname: Tommasi
authors.forename: Brian M
authors.initials: BM
authors.lastname: Westwood
authors.forename: Michael E
authors.initials: ME
authors.lastname: Robbins
authors.forename: Mark C
authors.initials: MC
authors.lastname: Chappell
authors.forename: Debra I
authors.initials: DI
authors.lastname: Diz
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012044:Regression Analysis; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics*; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors
chemical_list: D007093:Imidazoles; D020738:Leptin; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000808:Angiotensinogen; C070967:L 158809; D054637:Dual-Specificity Phosphatases; D007703:Peptidyl-Dipeptidase A