Nephrology Dialysis Transplantation, Vol 13, Issue 3 594-601, Copyright © 1998 by Oxford University Press
D Tan, M Cernadas, P Aragoncillo, M Castilla, M Arroyo, A Farre, S Casad and C Caramelo
Background: The impaired renal function and
vasodilatation that accompany age need to be re-addressed based upon the
new knowledge concerning vascular nitric oxide (NO)-dependent systems. The
present study examined the effects of age on the NO-related renal response.
Methods: The study was performed in euvolaemic,
conscious Wistar rats, aged 5 and 18 months. Renal function and
haemodynamic measurements with fluorescent microspheres were employed to
assess differences between groups. Results: A first
set of experiments showed that ageing rats had a reduced natriuretic and
diuretic response to acetylcholine, whereas the response to sodium
nitroprusside was preserved. In the same regard, a reduction of the renal
functional effects of L-arginine
(L-Arg) and L-glycine
(L-Gly) was found in the older rats. In the ageing
rats, these responses were accompanied by an enhanced effect of the
L-Arg competitive analogue NwNLA, which provoked
marked reduction on renal function. This effect of NwNLA was blocked by the
simultaneous administration of a small dose of L-Arg
in the ageing but not in the young rats. Systemic haemodynamic studies
revealed that in ageing rats, NwNLA reduced renal blood flow and increased
renal vascular resistances in a significantly higher proportion than in
younger animals. However flow to other organs, namely, brain, spleen or
liver, was affected in a similar manner in both young and old rats.
Ultrastructural alterations were found in endothelial cells, which might
constitute the anatomical basis for the observed functional derangements.
Conclusions: The present experiments reveal that
ageing is accompanied by significant differences in NO-related responses in
the kidney which do not appear to affect blood flow to other organs. The
response to L-Arg and L-Arg
competitive analogues supports the existence of a marked dependency on
NO-related mechanisms in the ageing rats, but not of a decreased baseline
activity of the NO-dependent pathways. Key words:
ageing; L-arginine;
L-glycine; renal function
ORIGINAL ARTICLES
Role of nitric oxide-related mechanisms in renal function in ageing rats
Laboratoire de Nefrologia, Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, Reyes Catolicos 2, E-28040 Madrid,Spain; Servicio de Anatomia Patologica, Hospital Clinico de San Carlos, Universidad Complutense, Madrid, Spain; Corresponding author
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