Department of Physiology, The University of Melbourne, Parkville, Victoria 3052, Australia
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ABSTRACT |
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Atrial natriuretic factor (ANF) and nitric oxide (NO) stimulate
production of guanosine 3',5'-cyclic monophosphate (cGMP) and are natriuretic. Split-drop micropuncture was performed on anesthetized rats to determine the effects of ANF and the NO donor sodium nitroprusside (SNP) on proximal tubular fluid absorption rate
(Jva). Compared
with control solutions, SNP
(104 M) decreased
Jva by 23% when
administered luminally and by 35% when added to the peritubular
perfusate. Stimulation of fluid uptake by luminal angiotensin II (ANG
II; 10
9 M) was abolished by
SNP (10
4 and
10
6 M). In proximal tubule
suspensions, ANF (10
6 M)
increased cGMP concentration to 143%, whereas SNP
(10
6,
10
5,
10
4,
10
3 M) raised cGMP to 231, 594, 687, and 880%, respectively.
S-nitroso-N-acetylpenicillamine (SNAP) also raised cGMP concentrations with similar dose-response relations. These studies demonstrate inhibition by luminal and peritubular NO of basal and ANG II-stimulated proximal fluid absorption in vivo. The ability of SNP to inhibit basal fluid uptake whereas ANF
only affected ANG II-stimulated transport may be because of production
of higher concentrations of cGMP by SNP.
guanosine 3',5'-cyclic monophosphate; guanylyl cyclase; angiotensin II; sodium nitroprusside; S-nitroso-N-acetylpenicillamine; renal micropuncture
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INTRODUCTION |
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ATRIAL NATRIURETIC FACTOR (ANF) and nitric oxide (NO) exert potent effects on renal blood flow, glomerular hemodynamics, and sodium excretion by actions mediated by the second messenger guanosine 3',5'-cyclic monophosphate (cGMP) (1, 5, 15, 16, 18). In the rat proximal convoluted tubule in vivo, ANF has been shown to affect proximal tubular fluid absorption by inhibiting the stimulatory action of low concentrations of angiotensin II (ANG II) (12), whereas ANF alone had no effect on fluid absorption. Garvin (8) reported similar findings using perfused isolated rat proximal straight tubules and, in addition, demonstrated inhibition of ANG II-stimulated fluid transport by dibutyryl cGMP.
The effect of NO on proximal tubular Na+ transport has been addressed by several studies but remains controversial. Inhibition of NO decreased fractional lithium excretion (1, 22), indicating that NO reduces Na+ reabsorption, whereas other workers have reported that NO synthase inhibition reduced proximal Na+ transport and concluded that NO stimulates proximal reabsorption. More recently, Roczniak and Burns (25) have demonstrated that NO donors induce stimulation of soluble guanylyl cyclase, production of cGMP, and inhibition of an amiloride-sensitive Na+/H+ exchanger in rabbit proximal tubules and primary cell cultures.
The presence of the guanylyl cyclase-coupled ANF receptor in proximal tubules is indicated by microlocalization of specific mRNA for this receptor (29) and by our observation that ANF raises intracellular cGMP concentration (6) in these cells. In addition, many cells contain a cytosolic NO-sensitive guanylyl cyclase, but, although mRNA for subunits of soluble guanylyl cyclase has been detected in the interlobular artery as well as afferent and collecting duct arterioles (14), mRNA for this enzyme has not yet been detected in proximal tubules. Functional evidence for the activity of soluble guanylyl cyclase in these cells is provided by Roczniak and Burns (25), who found that a specific inhibitor of this enzyme attenuated the stimulation of cGMP production by NO.
We determined the effects on cGMP concentrations of addition of ANF,
sodium nitroprusside (SNP), and
S-nitroso-N-acetylpenicillamine (SNAP) to freshly isolated rat proximal tubules and, in split-droplet micropuncture experiments, investigated the effects of luminal or
peritubular addition of SNP on proximal tubular fluid absorption. The
results demonstrate that NO stimulates cGMP production with a maximum
response greater than that achieved with ANF. The NO donor SNP
(104 M) at a concentration
which stimulates cGMP levels 4.2-fold compared with ANF
(10
6 M) inhibited ANG
II-stimulated fluid uptake and, in contrast to ANF
(10
6 M), also reduced basal
unstimulated rates of fluid absorption. However, SNP
(10
6 M) at a concentration
that raised cGMP to a similar level as ANF
(10
6 M) did not affect
basal rates of fluid absorption but, like ANF, inhibited ANG
II-stimulated fluid uptake.
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METHODS |
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Micropuncture.
Adult male Sprague-Dawley rats were anesthetized with Inactin (110 mg/kg ip) and infused intravenously with 0.9% NaCl at 1.6 ml · h1 · 100 g body wt
1. The left kidney
was prepared for micropuncture (11), and, after an equilibration period
of 1-2 h, shrinking split-drop microperfusion was performed in
midproximal convoluted tubule segments
(S2) visible on the kidney
surface. Sudan Black-stained castor oil was first introduced into a
proximal tubule from one barrel of a double-barreled micropipette. An
artificial tubular fluid solution (145 mM NaCl, 5 mM
NaHCO3, 5 mM KCl, and 1.5 mM
CaCl2) was then injected from the other barrel to split the oil column. The rate of shrinking of the
split-drop was determined by digital image analysis of the positions of
the oil-water menisci in successive video frames captured at 1-s
intervals (11). In a group of seven rats, proximal fluid uptake rate
per unit surface area of epithelium
(Jva) was determined in three to five tubules, and a mean value was calculated. Fluid absorption rate was then determined in a further three or more
tubules using intratubular fluid containing the NO donor SNP
(10
6 or
10
4 M). In two separate
groups of 10 rats, fluid absorption during perfusion with control
solution was compared with fluid uptake during perfusion with a similar
fluid containing ANG II
(10
9 M) and then with fluid
containing ANG II (10
9 M)
and SNP (10
4 M) or SNP
(10
6 M) together.
Preparation of proximal tubule suspensions. Suspensions of renal proximal tubules were prepared using a modification of the procedures described by Wrenn et al. (31) and Schlatter et al. (27). Seven Sprague-Dawley rats (200-230 g; Austin Hospital, Melbourne, Australia) were anesthetized with Nembutal (phenobarbitone sodium, 6-10 mg/100 g body wt ip; Boehringer Fugelliem, Artarmon, New South Wales, Australia). A cannula (0.86 mm ID; 1.52 mm OD) was inserted into the abdominal aorta and used to perfuse both kidneys simultaneously with 40-60 ml of an ice-cold isotonic buffer (pH 7.5) containing (in mM) 130 NaCl, 5 NaHCO3, 1.6 Na2HPO4, 0.4 NaH2PO4, 1.3 CaCl2, 5 KCl, 1 MgSO4, 10 sodium acetate, 10 N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), 3 glucose, and 2 glycine. The kidneys were then perfused with a further 40-60 ml of this solution containing ~1% (wt/vol) magnetic iron oxide particles (carbonyl iron, Sigma). This suspension was filtered before use, first through a 60-µm and then through a 10-µm nylon mesh. The kidneys were then removed and decapsulated, and the cortex was carefully separated and chopped into small pieces with a scalpel. The tissue was digested at 37°C for 20 min in a horizontal shaking waterbath (50 revolutions/min) in the above buffer containing 1 mg/ml collagenase (type 4, Worthington Biochemical) and 2 IU/ml protease (Pronase E, Sigma Chemical). The resulting suspension was filtered once through a 200-µm mesh sieve and washed by sedimentation in a 200-ml beaker. The suspension of tubules and glomeruli was then placed in a 10-ml tube and passed four to six times through a magnetic field to allow separation of small vessels and glomeruli containing trapped iron oxide. The remaining tissue, consisting mainly of proximal tubules, was resuspended in cold (4°C) buffer and examined under dark-field illumination using a stereo microscope. Contaminating vascular tissue and glomeruli were separated using fine needles and removed by aspiration.
Treatment of isolated proximal tubules with ANF and SNP.
Suspensions of proximal tubules were stored on ice until use. Aliquots
(90 µl containing 200-700 µg protein) of suspension were
incubated in polypropylene tubes for 3 min at 37°C in a horizontal shaking waterbath. ANF (Auspep, Victoria, Australia), SNP (May and
Baker), or SNAP (Sapphire Bioscience, New South Wales, Australia) was
dissolved in HEPES buffer (as described above), and 10 µl were added
to experimental tubes to give final concentrations of ANF, SNP, or SNAP
as indicated. A similar volume of buffer was added to control tubes.
The SNP and SNAP solutions were made up immediately before use. The
suspension was mixed by manual agitation and reincubated for 1 min at
37°C in the waterbath. The reaction was stopped by adding 100 µl
ice-cold 10% perchloric acid. The tubes were placed on ice for
15-30 min and then centrifuged for 3 min at 10,000 g in a microcentrifuge. Aliquots (190 µl) of the supernatant were placed in new tubes for neutralization as
described by Sharps and McCarl (28). Briefly, samples were brought to a
total volume of 600 µl by adding distilled water, vigorously mixed
with 700 µl of a mixture (1:1, vol/vol) of
tri-n-octylamine (Sigma Chemical) and
1,1,2-trichloro-trifluoroethane (Sigma Chemical), and then centrifuged
at 10,000 g in a microcentrifuge for 1 min. A portion (300 µl) of the top layer was carefully removed,
freeze dried, and stored at 20°C while awaiting assay for
cGMP.
Measurement of cGMP. cGMP concentration in cell extracts was determined by a specific radioimmunoassay (19). Acetylated standards and sample extracts were prepared using synthetic cGMP (Sigma Chemical) as described by Marley et al. (20). Protein concentrations were determined according to the method of Lowry et al. (17).
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RESULTS |
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Effect of luminal addition of SNP.
The effect on proximal tubular fluid absorption of luminal addition
of SNP is shown in Fig. 1. At a
concentration of 106
M, SNP had no effect on net fluid uptake, but at
10
4 M, SNP significantly
reduced mean Jva
by 23% compared with the uptake rate measured using control tubular
fluid alone (1.89 ± 0.16 vs. 2.53 ± 0.24 × 10
4
mm3 · mm
2 · s
1).
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Effect of peritubular perfusion with SNP.
As shown in Fig. 2, addition of SNP
(104 M) to the peritubular
capillary perfusate resulted in a decrease in mean
Jva by 35% compared with perfusion with control solution (1.71 ± 0.11 vs. 1.11 ± 0.22 × 10
4
mm3 · mm
2 · s
1).
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Effect of SNP on ANG II-stimulated fluid transport.
As shown in Fig. 3, in six of nine animals,
addition of ANG II
(109 M) to the intratubular
solution increased the mean rate of fluid uptake by 34% compared
with control (3.03 ± 0.13 vs. 2.26 ± 0.16 × 10
4
mm3 · mm
2 · s
1).
When ANG II (10
9 M) and SNP
(10
4 M) were
added together to the intratubular solution fluid, absorption rate was
reduced to the control level (2.41 ± 0.24 × 10
4
mm3 · mm
2 · s
1).
In the remaining three animals in this group, no response to ANG II was
observed, and these animals were not included in the subsequent
analysis.
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Effect of ANF and SNP on cGMP levels in proximal tubule suspensions.
Incubation of proximal tubules with ANF
(106 M) for 1 min resulted
in an increase (1.4-fold) of cGMP concentration from 37 ± 4 to 53 ± 6 fmol/mg protein (Fig. 5). SNP
increased accumulation of cGMP at concentrations of
10
6,
10
5,
10
4, and
10
3 M from 35 ± 1.4 to
81 ± 12, 208 ± 33, 241 ± 41, and 308 ± 66 fmol/mg protein, respectively (Fig. 6).
SNAP increased accumulation of cGMP at concentrations of
10
5,
10
4,
10
3, and
10
2 M from 37 ± 1.5 to
68 ± 13, 238 ± 102, 337 ± 18, and 377 ± 110 fmol/mg
protein, respectively (Fig. 7). Higher
concentrations of ANF (10
5
M) failed to elicit any further increases in cGMP levels in tubules from Wistar-Kyoto rats, indicating that the response obtained was
maximal.
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DISCUSSION |
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The data presented demonstrate that NO acts to inhibit sodium and water
reabsorption in the rat proximal convoluted tubule. This action was
observed when the NO donor SNP at
104 M, a concentration that
raised cGMP about sevenfold above control levels, was added to the
luminal fluid and when SNP
(10
4 M) was perfused into
the peritubular capillaries. SNP at
10
6 M, a
concentration which raised cGMP 2.3-fold, added to the luminal fluid
had no effect on basal sodium and water reabsorption, but luminal SNP
at 10
4 and
10
6 M abolished
the stimulatory action of intratubular ANG II on fluid uptake. SNP and
ANF both increased cGMP concentrations in isolated proximal tubules,
but the maximum response observed with SNP was approximately six times
greater than with ANF.
Previous reports have suggested that the proximal tubule is a site of action for NO (1, 22). It has also been demonstrated in primary cultures of rabbit proximal tubule cells that NO donors inhibit amiloride-sensitive 22Na+ uptake used as an indicator of Na+/H+ exchanger activity (25). Our work confirms the presence of functional NO-sensitive guanylyl cyclase in rat proximal tubules and shows that, in vivo, NO acts to inhibit transepithelial Na+ and water absorption.
The NO donor SNP was effective in reducing net fluid absorption whether added to the luminal or peritubular sides of the tubular epithelium. Evidence based on the detection of mRNA for various isoforms of nitric oxide synthase (NOS) in rat kidney indicates that NO could be produced in endothelial cells adjacent to the proximal tubule (21) or in the proximal tubule cells themselves (30). NO produced by endothelial NO synthase could diffuse into the epithelial cells to act on the soluble guanylyl cyclase, or locally produced NO might act in an autocrine manner to affect production of cGMP.
Administration of ANF resulted in increased intracellular cGMP levels in isolated proximal tubules (Fig. 4). The NO donors SNP and SNAP increased cGMP levels in a dose-dependent manner (Figs. 6 and 7). The data reported here indicate that NO is considerably more effective than ANF in raising cGMP concentration. Our results do not provide an explanation for this difference, but it is likely that the data reflect the relative activity or abundance of the soluble guanylyl cyclase activated by NO compared with the membrane-bound guanylyl cyclase ANF receptor.
The cellular mechanisms by which cGMP might act as a common messenger
for the actions of both NO and ANF are not directly addressed by our
experiments. However, some insight into these mechanisms is provided by
the ability of NO to inhibit ANG II-stimulated fluid absorption (Figs.
3 and 4). We have previously reported that ANF, when added to the
peritubular fluid, inhibited ANG II-stimulated fluid transport in the
rat proximal convoluted tubule, although ANF alone had no effect (12).
Garvin (8) confirmed these findings in perfused, isolated tubules and
demonstrated that ANG II-stimulated transport was also inhibited by the
membrane-permeant analog dibutyryl cGMP. In the present experiments, in
animals in which proximal fluid uptake in split-drops was stimulated by addition of ANG II to the intratubular fluid, absorption rate returned
to control levels when SNP was added to the luminal fluid together with
ANG II. We infer that NO diffuses into proximal tubule cells and
stimulates soluble guanylyl cyclase, resulting in accumulation of cGMP.
This nucleotide then acts to modulate the cellular processes involved
in the stimulatory action of ANG II on transepithelial Na+
transport, resulting in restoration of fluid transport rate to the
control level. Variation in proximal tubule responsiveness to ANG II
has also been reported by Coppola and Fromter (4), who applied a
concentration of 1011 M to
the bathing solution of perfused, isolated rabbit proximal tubules. In
85% of tubules tested, there was a small depolarization, whereas the
remaining 15% responded with a small hyperpolarization. The cause of
these variations in responsiveness remains unclear, but it is known
that ANG II is produced within proximal tubule cells and secreted into
the lumen (2) where it can affect the rate of fluid uptake (13).
Differences in the rate of secretion of locally produced ANG II might
be responsible for variations in the basal rate of sodium reabsorption
and for differences in responsiveness to addition of exogenous peptide.
Modulation of proximal tubular sodium transport by ANF or cGMP is thought to involve cGMP-dependent phosphorylation of a target protein, since KT-5823, a cGMP-dependent protein kinase inhibitor, blocked the action of ANF on ANG II-stimulated fluid absorption in the isolated perfused rat proximal tubule (7). Several other mechanisms have been implicated in the proximal actions of ANF, and these appear to be activated independently of stimulation by ANG II or any other hormone or norepinephrine. The majority of reports have supported the view that ANF alone does not affect proximal Na+ transport (8, 12), although Hammond et al. (10) demonstrated inhibition of Na+/H+ exchange and Na+-dependent Pi uptake in proximal brush-border membrane vesicles from rats pretreated by infusion of ANF.
ANF has also been shown to increase
Ca2+-Mg2+-ATPase
activity in basolateral membranes isolated from rat kidney, and its
action on epithelial Na+ transport
may involve altered intracellular
Ca2+ homeostasis (26). Reddy et
al. (24) found cell swelling in response to ANF in proximal tubule
cells from rat kidneys examined using electron microprobe X-ray
analysis and concluded that ANF, presumably acting through cGMP,
inhibits the Na+ pump. A further mechanism involves a
cGMP-activated Cl channel
found in cultured rat proximal convoluted tubule cells (23) that could
mediate the action of ANF by allowing
Cl
to leave the cells and
thus reduce the lumen-positive driving force for
Na+ reabsorption.
Although there is little evidence for a direct action of ANF acting alone to influence proximal tubular reabsorption, our experiments show that NO inhibited not only ANG II-stimulated transport (Fig. 3) but also reduced fluid uptake in the absence of peritubular ANG II (Fig. 2). The inhibitory effect of luminal addition of SNP on fluid uptake shown in Fig. 1 was observed under conditions of normal blood perfusion through the peritubular capillaries, and it is likely that this blood contained ANG II at a concentration expected to exert a stimulatory action on fluid transport (32). In support of a direct action of NO on proximal tubular transport, Roczniak and Burns (25) found that NO donors inhibit Na+/H+ exchange activity determined by amiloride-sensitive 22Na+ uptake in primary cultures of rabbit proximal tubules, and Guzman et al. (9) have reported an inhibitory action of NO on the Na+-K+-ATPase in cultured mouse proximal tubule cells. These actions of NO appear to be dependent at least in part on the generation of cGMP but may also involve the production of peroxynitrite radicals or activation of other cGMP-independent pathways that might act to modulate transporter activities.
A recent study by Chevalier et al. (3) on LLC-PK1 cells suggests that during treatment with an NO donor, cGMP is transported out of proximal tubule cells by a probenecid-sensitive organic anion transporter and acts in an autocrine fashion to alter transepithelial Na+ transport. Our experiments do not enable us to identify an action of extracellular cGMP in response to NO, but neither do they exclude such an action. Perfusion of peritubular capillaries during in vivo micropuncture experiments provides a means for delivery of known concentrations of hormones and for exclusion of circulating factors. However, cGMP extruded from the cells into the interstitial fluid or into the lumen would still be available to influence cellular function.
Our finding that ANF and SNP
(106 M) inhibit only ANG
II-stimulated transport, whereas SNP
(10
4 M) also affects fluid
uptake in the absence of any apparent stimulation by ANG II may be
because of the different levels of cGMP production. Although ANF raised
cGMP in our preparation of proximal tubule suspensions only 1.4-fold
and SNP (10
6 M) 2.3-fold
above control levels in 1 min, SNP
(10
4 M) raised cGMP
6.5-fold under the same conditions. The concentration of cGMP reached
within or around the proximal tubule cell may therefore determine which
of the various regulatory pathways involved in control of
transepithelial sodium transport are influenced by delivery of
extracellular modulators such as ANF and NO.
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ACKNOWLEDGEMENTS |
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We are grateful to Dr. Philip Marley for the supply of radiolabeled nucleotide and antibody for the cGMP assay.
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FOOTNOTES |
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This work was supported by the National Health and Medical Research Council of Australia.
Address reprint requests to P. J. Harris.
Received 9 December 1996; accepted in final form 12 December 1997.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Alberola, A.,
J. M. Pinilla,
T. Quesada,
J. C. Romero,
M. G. Salom,
and
F. J. Salazar.
Role of nitric oxide in mediating renal response to volume expansion.
Hypertension
19:
780-784,
1992[Abstract].
2.
Braam, B.,
K. D. Mitchell,
J. Fox,
and
L. G. Navar.
Proximal tubular secretion of angiotensin II in rats.
Am. J. Physiol.
264 (Renal Fluid Electrolyte Physiol. 33):
F891-F898,
1993
3.
Chevalier, R. L.,
G. D. Fang,
and
M. Garmey.
Extracellular cGMP inhibits transepithelial sodium transport by LLC-PK1 renal tubular cells.
Am. J. Physiol.
270 (Renal Fluid Electrolyte Physiol. 39):
F283-F288,
1996
4.
Coppola, S.,
and
E. Fromter.
An electrophysiological study of angiotensin II regulation of Na-HCO3 cotransport and K conductance in renal proximal tubules. I. Effect of picomolar concentrations.
Pflügers Arch.
427:
143-150,
1994[Medline].
5.
De Nicola, L.,
R. C. Blantz,
and
F. B. Gabbai.
Nitric oxide and angiotensin II: glomerular and tubular interaction in the rat.
J. Clin. Invest.
89:
1248-1256,
1992[Medline].
6.
Eitle, E.,
P. J. Harris,
and
T. O. Morgan.
Effects of atrial natriuretic factor on cyclic nucleotides in rabbit proximal tubule.
Hypertension
23:
358-363,
1994[Abstract].
7.
Garcia, N. H.,
and
J. L. Garvin.
ANF and angiotensin II interact via kinases in the proximal straight tubule.
Am. J. Physiol.
268 (Renal Fluid Electrolyte Physiol. 37):
F730-F735,
1995
8.
Garvin, J. L.
Inhibition of Jv by ANF in rat proximal straight tubules requires angiotensin.
Am. J. Physiol.
257 (Renal Fluid Electrolyte Physiol. 26):
F907-F911,
1989
9.
Guzman, N. J.,
M. Fang,
S. S. Ang,
J. R. Ingelfinger,
and
L. C. Garg.
Autocrine inhibition of Na+/K+-ATPase by nitric oxide in mouse proximal tubule epithelial cells.
J. Clin. Invest.
95:
2083-2088,
1995[Medline].
10.
Hammond, T. G.,
A. N. K. Yusifi,
F. G. Knox,
and
T. P. Dousa.
Administration of atrial natriuretic factor inhibits sodium-coupled transport in proximal tubules.
J. Clin. Invest.
75:
1983-1989,
1985[Medline].
11.
Harris, P. J.,
M. Cullinan,
D. Thomas,
and
T. O. Morgan.
Digital image capture and analysis for split-drop micropuncture.
Pflügers Arch.
408:
615-618,
1987[Medline].
12.
Harris, P. J.,
D. Thomas,
and
T. O. Morgan.
Atrial natriuretic peptide inhibits angiotensin-stimulated proximal tubular sodium and water reabsorption.
Nature
326:
697-698,
1987[Medline].
13.
Hiranyachattada, S.,
and
P. J. Harris.
Modulation by locally produced luminal angiotensin II of proximal tubular sodium reabsorption via an AT1 receptor.
Br. J. Pharmacol.
119:
617-618,
1996[Abstract].
14.
Kazatomo, U.,
J. Yuen,
and
L. Hogarth.
Localization and regulation of endothelial NO synthase mRNA expression in rat kidney.
Am. J. Physiol.
267 (Renal Fluid Electrolyte Physiol. 36):
F296-F302,
1994
15.
Lahera, V.,
J. Navarro,
M. L. Biondi,
L. M. Ruilope,
and
J. C. Romero.
Exogenous cGMP prevents decrease in diuresis and natriuresis induced by inhibition of NO synthesis.
Am. J. Physiol.
264 (Renal Fluid Electrolyte Physiol. 33):
F344-F347,
1993
16.
Lahera, V.,
M. G. Salom,
F. Miranda-Guardiola,
S. Moncada,
and
J. C. Romero.
Effects of NG-nitro-L-arginine methyl ester on renal function and blood pressure.
Am. J. Physiol.
261 (Renal Fluid Electrolyte Physiol. 30):
F1033-F1037,
1991
17.
Lowry, O. H.,
N. J. Rosebrough,
A. L. Farr,
and
R. J. Randall.
Protein measurement with the Folin phenol reagent.
J. Biol. Chem.
193:
265-275,
1951
18.
Majid, D. S. A.,
A. Williams,
and
L. G. Navar.
Inhibition of nitric oxide synthesis attenuates pressure-induced natriuretic responses in anesthetized dogs.
Am. J. Physiol.
264 (Renal Fluid Electrolyte Physiol. 33):
F79-F87,
1993
19.
Marley, P. D.,
and
K. A. Thomson.
Regulation of cyclic AMP metabolism in bovine adrenal medullary cells.
Biochem. Pharmacol.
44:
2105-2110,
1992[Medline].
20.
Marley, P. D.,
K. A. Thomson,
K. Jachno,
and
M. J. Johnston.
Histamine-induced increase in cAMP levels in bovine adrenal medullary cells.
Br. J. Pharmacol.
104:
839-846,
1991[Abstract].
21.
Mohaupt, M. G.,
J. L. Elzie,
K. Y. Ahn,
W. L. Clapp,
C. S. Wilcox,
and
B. C. Kone.
Differential expression and induction of mRNAs encoding two inducible nitric oxide synthases in rat kidney.
Kidney Int.
46:
653-665,
1994[Medline].
22.
Nakamura, T.,
A. M. Alberola,
and
J. P. Granger.
Role of renal interstitial pressure as a mediator of sodium retention during systemic blockade of nitric oxide.
Hypertension
21:
956-960,
1993[Abstract].
23.
Nissim, D.,
J. Winaver,
and
D. Dagan.
A novel cGMP-activated Cl channel in renal proximal tubules.
Am. J. Physiol.
268 (Renal Fluid Electrolyte Physiol. 37):
F323-F329,
1995
24.
Reddy, S.,
A. Z. Gyory,
M. Dyne,
N. Salipan-Moore,
C. Pollock,
M. J. Field,
and
D. J. H. Cockayne.
Effect of atrial natriuretic peptide on cellular element concentrations in rat proximal tubules: evidence for inhibition of the sodium pump.
Clin. Exp. Pharmacol. Physiol.
21:
775-780,
1994[Medline].
25.
Roczniak, A.,
and
K. D. Burns.
Nitric oxide stimulates guanylate cyclase and regulates sodium transport in rabbit proximal tubule.
Am. J. Physiol.
270 (Renal Fluid Electrolyte Physiol. 39):
F106-F115,
1996
26.
Sahai, A.,
and
P. K. Ganguly.
Lack of response of (Ca2++Mg2+) ATPase to atrial natriuretic peptide in basolateral membranes from kidney cortex of chronic diabetic rats.
Biochem. Biophys. Res. Commun.
169:
537-544,
1990[Medline].
27.
Schlatter, E.,
U. Frobe,
and
R. Greger.
Ion conductances of isolated cortical collecting duct cells.
Pflügers Arch.
421:
381-387,
1992[Medline].
28.
Sharps, E. S.,
and
R. L. McCarl.
A high-performance liquid chromatographic method to measure 32P incorporation into phosphorylated metabolites in cultured cells.
Anal. Biochem.
124:
421-424,
1982[Medline].
29.
Terada, Y.,
T. Moriyama,
B. M. Martin,
M. A. Knepper,
and
A. Garcia-Perez.
RT-PCR microlocalization of mRNA for guanylyl cyclase-coupled ANF receptor in rat kidney.
Am. J. Physiol.
261 (Renal Fluid Electrolyte Physiol. 30):
F1080-F1087,
1991
30.
Ujiie, K.,
J. Yuen,
L. Hogarth,
R. Danziger,
and
R. A. Star.
Localization and regulation of endothelial NO synthase mRNA expression in rat kidney.
Am. J. Physiol.
267 (Renal Fluid Electrolyte Physiol. 36):
F296-F302,
1994
31.
Wrenn, R. W.,
M. G. Currie,
and
D. M. Biddulph.
Influence of calcium, parathyroid hormone and ionophore A-23187 on cyclic nucleotide concentrations of isolated renal tubules.
Mol. Cell. Endocrinol.
10:
263-276,
1978[Medline].
32.
Zhuo, J.,
D. Thomas,
P. J. Harris,
and
S. L. Skinner.
The role of endogenous angiotensin II in the regulation of renal haemodynamics and proximal reabsorption.
J. Physiol. (Lond.)
453:
1-13,
1992[Abstract].