Sexual dimorphism in the aging kidney: Effects on injury and nitric oxide system.
BACKGROUND
Male gender confers enhanced susceptibility to development of age-dependent kidney damage. In other models of progressive renal disease, development of injury is linked to declines in renal nitric oxide synthase (NOS) capacity.


METHODS
We investigated the in vitro characteristics of the renal NOS system in young (3 to 5 months), middle-aged (11 to 13 months) and old (18 to 22 months) male and female Sprague-Dawley rats.


RESULTS
NOS activity (pmol [3H]-arginine converted to [3H]-citrulline/mg protein/minute) is reduced in the soluble fraction of renal cortex from old versus young males but not females. In contrast, NOS activity in the soluble fraction of cerebellum is not altered by age or gender. The abundance of endothelial NOS (eNOS) and neuronal (nNOS) is reduced in renal cortex of old versus young males but is unchanged in female cortex. In renal medulla, eNOS protein is reduced with age in both males and females. We found no difference in abundance of either eNOS or nNOS protein in the cortex of young male and female rats. The incidence and severity of glomerular damage increases markedly with age in the male and only slightly in the female.


CONCLUSIONS
These findings indicate that a relative reduction occurs in renal NOS in the male kidney with advancing age, whereas NOS protein and activity is maintained during aging in females. This, together with the marked age-dependent kidney damage seen in the male, suggests that the renal NO deficiency in the aging male rat may contribute to the age-dependent kidney damage.
Erdely
Aaron
A
Department of Physiology, West Virginia University, Morgantown, West Virginia 26506-9229, USA.
Greenfeld
Ziv
Z
Wagner
Laszlo
L
Baylis
Chris
C
D000375:Aging / Q000502:physiology*; D000818:Animals; D005260:Female; D007672:Kidney Cortex / Q000378:metabolism*; D007674:Kidney Diseases / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat