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Departments of Medicine and Physiology and Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama 35294
The present
studies were performed to assess
Na+/Ca2+
exchange activity in afferent and efferent arterioles from Dahl/Rapp
salt-resistant (R) and salt-sensitive (S) rats. Renal arterioles were
obtained by microdissection from S and R rats on either a low-salt
(0.3% NaCl) or high-salt (8.0% NaCl) diet. On the high-salt diet, S rats become markedly hypertensive. Cytosolic calcium concentration ([Ca2+]i)
was measured in fura 2-loaded arterioles bathed in a Ringer solution in
which extracellular Na (Nae) was
varied from 150 to 2 mM (Na was replaced with
N-methyl-D-glucamine).
Baseline
[Ca2+]i
was similar in afferent arterioles of R and S rats fed low- and
high-salt diet. The change in
[Ca2+]i
(
[Ca2+]i)
during reduction in Nae from 150 to 2 mM was 80 ± 10 and 61 ± 3 nM (not significant) in afferent
arterioles from R rats fed the low- and high-salt diet, respectively.
In afferent arterioles from S rats on a high-salt diet,
[Ca2+]i
during reductions in Nae from 150 to 2 mM was attenuated (39 ± 4 nM) relative to the
[Ca2+]i
of 79 ± 13 nM (P < 0.05)
obtained in afferent arterioles from S rats on a low-salt diet. In
efferent arterioles, baseline
[Ca2+]i
was similar in R and S rats fed low- and high-salt diets, and
[Ca2+]i
in response to reduction in Nae
was also not different in efferent arterioles from R and S rats fed
low- or high-salt diets. Differences in regulation of the exchanger in
afferent arterioles of S and R rats were assessed by determining the
effects of protein kinase C (PKC) activation by phorbol 12-myristate
13-acetate (PMA, 100 nM) on
[Ca2+]i
in response to reductions in Nae
from 150 to 2 mM. PMA increased
[Ca2+]i
in afferent arterioles from R rats but not from S rats. These results
suggest that
Na+/Ca2+
exchange activity is suppressed in afferent arterioles of S rats that
are on a high-salt diet. In addition, there appears to be a defect in
the
PKC-Na+/Ca2+
exchange pathway that might contribute to altered
[Ca2+]i
regulation in this important renal vascular segment in salt-sensitive hypertension.
sodium/calcium exchange; protein kinase C; renal afferent and efferent arterioles
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