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1 Institut de Pharmacologie, Faculté de Médecine, Université Louis Pasteur; and 2 Service d'Hypertension, des Maladies Vasculaires et Pharmacologie Clinique, Hôpitaux Universitaires de Strasbourg, 67085 Strasbourg France
This study was designed to determine the
involvement of AT1 receptors in the uptake of ANG II in the
kidney of rats exposed to differing salt intake. Male Wistar-Kyoto rats
were treated with a normal-salt (NS; 1% NaCl, n = 7)
or a low-salt (LS; 0.025% NaCl, n = 7) diet combined
with (LS+Los, n = 7; NS+Los, n = 7) or
without losartan (30 mg · kg
1 · day1), an
AT1 receptor antagonist. Renin (RA) and
angiotensin-converting enzyme (ACE) activities and angiotensinogen, ANG
I, and ANG II levels were measured in plasma, renal cortex, and
medulla. In LS rats, in both plasma and renal cortex, the increase in
RA was associated with an increase in ANG I and ANG II levels compared with NS rats, but intrarenal ANG II levels increased more than ANG I
levels. In NS+Los rats, the increase in RA in plasma was followed by a
marked increase in plasma ANG I and ANG II levels compared with NS rats
whereas in the kidney the increase of renal RA was followed by a
decrease of the levels of these peptides. The same pattern was observed
in LS+Los rats, but the decrease in renal ANG II levels was much more
pronounced in LS+Los rats than in NS+Los rats. Our results suggest that
the increase in renal ANG II levels after salt restriction results
mainly from an uptake of ANG II, via AT1 receptors. Such
elevated intrarenal ANG II levels could contribute to maintain sodium
and fluid balance and arterial blood pressure during salt-deficiency states.
sodium-restricted diet; losartan; kidney; renin-angiotensin system
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