title: Sexual dimorphism in development of kidney damage in aging Fischer-344 rats.
abstract: BACKGROUND
  Aging kidneys exhibit slowly developing injury and women are usually protected compared with men, in association with maintained renal nitric oxide.
  
  
  OBJECTIVE
  Our purpose was to test 2 hypotheses: (1) that aging intact Fischer-344 (F344) female rats exhibit less glomerular damage than similarly aged males, and (2) that loss of female ovarian hormones would lead to greater structural injury and dysregulation of the nitric oxide synthase (NOS) system in aging F344 rat kidneys.
  
  
  METHODS
  We compared renal injury in F344 rats in intact, ovariectomized, and ovariectomized with estrogen replaced young (6 month) and old (24 month) female rats with young and old intact male rats and measured renal protein abundance of NOS isoforms and oxidative stress.
  
  
  RESULTS
  There was no difference in age-dependent glomerular damage between young or old intact male and female F344 rats, and neither ovariectomy nor estrogen replacement affected renal injury; however, tubulointerstitial injury was greater in old males than in old females. These data suggest that ovarian hormones do not influence these aspects of kidney aging in F344 rats and that the greater tubulointerstitial injury is caused by male sex. Old males had greater kidney cortex NOS3 abundance than females, and NOS1 abundance (alpha and beta isoforms) was increased in old males compared with both young males and old females. NOS abundance was preserved with age in intact females, ovariectomy did not reduce NOS1 or NOS3 protein abundance, and estrogen replacement did not uniformly elevate NOS proteins, suggesting that estrogens are not primary regulators of renal NOS abundance in this strain. Nicotinamide adenine dinucleotide phosphate oxidase-dependent superoxide production and nitrotyrosine immunoreactivity were increased in aging male rat kidneys compared with females, which could compromise renal nitric oxide production and/or bioavailability.
  
  
  CONCLUSIONS
  The kidney damage expressed in aging F344 rats is fairly mild and is not related to loss of renal cortex NOS3 or NOS1 alpha.
authors: Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA. jsasser@umc.edu
authors: Jennifer M
authors: JM
authors: Sasser
authors: Oladele
authors: O
authors: Akinsiku
authors: Natasha C
authors: NC
authors: Moningka
authors: Katie
authors: K
authors: Jerzewski
authors: Chris
authors: C
authors: Baylis
authors: Amanda J
authors: AJ
authors: LeBlanc
authors: Lori S
authors: LS
authors: Kang
authors: Amy L
authors: AL
authors: Sindler
authors: Judy M
authors: JM
authors: Muller-Delp
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007672:Kidney Cortex / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics
chemical_list: D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III