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Effects of Aging and Renin‐Angiotensin System (RAS) Blockade on the Intra‐renal RAS in Older Fischer 344 X Brown Norway Rats
Author(s) -
Kasper Sherry O,
GilliamDavis Shea,
Groban Leanne,
Carter Christy S,
Sonntag William E,
Chappell Mark C,
Diz Debra I
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.735.11
Subject(s) - blockade , medicine , endocrinology , enalapril , renal function , proteinuria , renin–angiotensin system , kidney , urinary system , blood pressure , angiotensin converting enzyme , receptor
Activation of the intrarenal RAS occurs during aging in Wistar, Sprague‐Dawley and Fischer 344 (F344) rats as indicated by increased urinary angiotensin (Ang) II and proteinuria, with or without systolic blood pressure elevations. Long‐term RAS blockade when started early (2–4 months of age) prevents intra‐renal RAS activation. The present study assessed the effects of aging and RAS blockade on kidney function in F344 X Brown Norway rats, a model of healthy aging in terms of overall longevity. Rats (n = 6 – 9/group) received daily subcutaneous injections of the ACE inhibitor enalapril (MED, 40 mg/kg; HIGH, 80 mg/kg) or saline (CON) for 6 months starting at 24 months of age; a young group (YO;9 months) was also studied. At 30 months of age, urine volume and body weight were similar among older groups and higher than YO rats. Urinary Ang II was significantly lower in older CON rats relative to YO rats, but did not differ among other groups (HIGH = 6 ± 1; MED = 7 ± 1; CON = 6 ± 1; YO = 11 ± 2 pmol/kg/day). Protein excretion did not increase in the older CON rats relative to YO animals and was not altered by treatment. Therefore, in animals with healthy aging there is a lack of activation of the intra‐renal RAS and no development of proteinuria. Moreover, in the absence of apparent age‐related indices of renal injury, there is no effect of long‐term RAS blockade on these variables. Support: HL51952, AHA‐MA021515U, AG026764, AG10484, AG11370