(Hypertension. 1996;27:72-78.)
© 1996 American Heart Association, Inc.
Articles |
Angiotensin II and Angiotensin-(1-7) Effects on Free Cytosolic Sodium, Intracellular pH, and the Na+-H+ Antiporter in Vascular Smooth Muscle
From the Department of Medicine, Division of Nephrology and Hypertension, Northwestern University Medical School, and Lakeside Veterans Administration Medical Center, Chicago, Ill.
Correspondence to Daniel Batlle, MD, Northwestern University Medical School, Division of Nephrology and Hypertension, 325 E Superior, Searle 10-475, Chicago, IL 60611.
Abstract The aim of the present study was to define the
effects of angiotensin II (Ang II) and Ang-(1-7) on free
cytosolic Na+ (Na+i), intracellular
pH (pHi), and the Na+-H+ antiporter
in cultured vascular smooth muscle cells from rat aorta. Cells were
loaded with either BCECF-AM or SBFI-AM for measurement of
pHi and Na+i, respectively.
Ang II (10-6 mol/L) caused a rapid rise in
Na+i followed by a progressive increase that
peaked at about 10 minutes (from 11±1.5 to 16±1.5 mmol/L,
P<.001), whereas Ang-(1-7) (10-6 mol/L) did
not affect Na+i significantly (from 11.5±1.1
to 11.8±0.07 mmol/L). The effect of Ang II on
Na+i was concentration dependent
(
Na+i, 5.1±0.9, 3.8±0.6,
1.6±0.6,
and 0.14±0.18 mmol/L with decreasing concentrations of
10-6, 10-7,
10-8, and 10-9 mol/L, respectively).
Ang II caused a brief acidification followed by an increase in
pHi (from 7.34±0.03 to 7.43±0.03 after 10 minutes,
P<.005), and Ang-(1-7) had no significant effect on
pHi (from 7.23±0.03 to 7.23±0.03). To investigate
whether
pHi and Na+i changes induced by Ang
II were due to cell Na+ entry via stimulation of the
Na+-H+ antiporter, we pretreated cells with
EIPA (25 µmol/L) or ouabain (2.0 mmol/L). Ang II in the presence of
ouabain caused a greater increase than that seen with ouabain alone
(Na+i, 13±1.5 versus 6.3±1.2
mmol/L, P<.0025). EIPA by itself decreased
Na+i and pHi. After EIPA, Ang II
failed to increase both Na+i and
pHi, demonstrating that the
Na+-H+ antiporter is responsible for the rises
in Na+i and pHi during stimulation
with Ang II. To further characterize the mechanism of Ang II action, we
exposed cells to an Ang II type 1 receptor antagonist
(L-158,809, 10-6 mol/L) or two different type 2 receptor
antagonists (PD 123177 and CGP 421112A, 10-6
mol/L). L-158,809 completely blocked the rise in pHi caused
by Ang II, whereas PD 123177 and CGP 421112A did not. We conclude that
Ang II increases both Na+i and
pHi, and both effects are mediated by stimulation of
the Na+-H+ antiporter. Ang-(1-7), by contrast,
has no significant effect on Na+i,
pHi, or the Na+-H+
antiporter. Stimulation of this antiporter by Ang II is exerted through
the type 1 receptor.
Key Words: muscle, smooth, vascular • angiotensins • sodium/hydrogen antiporter
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