Loss of nitric oxide and endothelial-derived hyperpolarizing factor-mediated responses in aging.
BACKGROUND
Aging has considerable structural and functional effects on the vascular system of the kidney. One such effect is an alteration in vascular tone which potentially will initiate renal damage. Vascular tone is determined by the balance between vasoconstrictors and vasodilators. Therefore, we hypothesized that aging attenuates vasodilatory responses in the kidney. These changes may be mediated by a loss of nitric oxide and endothelial-derived hyperpolarizing factor (EDHF).


METHODS
The systemic and renal responses of nitric oxide and EDHF were investigated in aging (18 months old) and young (3 months old) Sprague-Dawley rats.


RESULTS
We demonstrated a general loss of vasodilatory responses in the aging kidney. In addition, nitric oxide levels were reduced in the serum and kidney cortex of aging versus young animals, although this was not accompanied with a loss of endothelial nitric oxide synthase (eNOS) protein in the kidney cortex. Aging animals also exhibited a loss in EDHF-mediated vasodilation following stimulation with either acetylcholine or bradykinin in the isolated perfused kidney.


CONCLUSIONS
These findings indicate that not only a defect in the nitric oxide pathway, but also a loss of EDHF-mediated responses may be responsible for impaired vasodilation in the aging kidney. This may result in enhanced vasoconstrictive responses in aging which potentially will cause renal damage and ultimately a loss in glomerular filtration rate (GFR).
Long
David A
DA
Section of Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, USA. dlong@ich.ucl.ac.uk
Newaz
Mohammad A
MA
Prabhakar
Sharma S
SS
Price
Karen L
KL
Truong
Luan D
LD
Feng
Lili
L
Mu
Wei
W
Oyekan
Adebayo O
AO
Johnson
Richard J
RJ
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000098:blood supply / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D001685:Biological Factors; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine