Departments of 1 Pediatrics and 2 Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75235-9063
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ABSTRACT |
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The proximal tubule
synthesizes and luminally secretes high levels of angiotensin II, which
modulate proximal tubule transport independently of systemic
angiotensin II. The purpose of this in vivo microperfusion study is to
examine whether the renal nerves modulate the effect of intraluminal
angiotensin II on proximal tubule transport. The decrement in volume
reabsorption after addition of 104 M luminal enalaprilat
is a measure of the role of luminal angiotensin II on transport. Acute
denervation decreased volume reabsorption (2.97 ± 0.14 vs.
1.30 ± 0.21 nl · mm
1 · min
1,
P < 0.001). Although luminal 10
4 M
enalaprilat decreased volume reabsorption in controls (2.97 ± 0.14 vs. 1.61 ± 0.26 nl · mm
1 · min
1,
P < 0.001), it did not after acute denervation
(1.30 ± 0.21 vs. 1.55 ± 0.19 nl · mm
1 · min
1). After
chronic denervation, volume reabsorption was unchanged from sham
controls (2.26 ± 0.28 vs. 2.70 ± 0.19 nl · mm
1 · min
1). Addition
of luminal 10
4 M enalaprilat decreased volume
reabsorption in sham control (2.70 ± 0.19 vs. 1.60 ± 0.10 nl · mm
1 · min
1,
P < 0.05) but not with chronic denervation (2.26 ± 0.28 vs. 2.07 ± 0.20 nl · mm
1 · min
1). Addition
of 10
8 M angiotensin II to the lumen does not affect
transport due to the presence of luminal angiotensin II. However,
addition of 10
8 M angiotensin II to the tubular lumen
increased the volume reabsorption after both acute (1.30 ± 0.21 vs. 2.67 ± 0.18 nl · mm
1 · min
1,
P < 0.05) and chronic denervation (2.26 ± 0.28 vs. 3.57 ± 0.44 nl · mm
1 · min
1,
P < 0.01). These data indicate that renal denervation
abolished the luminal enalaprilat-sensitive component of proximal
tubule transport, which is consistent with the renal nerves playing a role in the modulation of the intraluminal angiotensin II mediated component of proximal tubule transport.
volume reabsorption; renal denervation; renin-angiotensin system
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INTRODUCTION |
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THE SYMPATHETIC RENAL NERVES richly innervate the proximal tubule and play an important role in the regulation of proximal tubule sodium reabsorption (1, 9, 10, 21). Stimulation of the renal nerves augments proximal tubule sodium reabsorption, whereas renal denervation decreases proximal tubule sodium reabsorption (3-5, 10). These effects occur independently of changes in the glomerular filtration rate, renal blood flow, and peritubular Starling forces and indicate that the renal nerves directly modulate proximal tubule transport (3-5, 10).
The stimulatory effect of the renal nerves on proximal tubule transport has been shown to be affected by systemic angiotensin II, a circulating hormone that also plays a regulatory role in proximal tubule transport (11, 14, 15). When circulating angiotensin II levels are decreased with saline loading or administration of DOCA or captopril, the increase in renal sodium reabsorption induced by renal nerve stimulation is markedly diminished (14). However, when angiotensin II levels are restored by systemic infusion at physiological levels that do not alter blood pressure, subsequent renal nerve stimulation augmented sodium reabsorption by the proximal tubule (14). These studies indicate that the renal nerves interact with the systemic renin-angiotensin system to regulate proximal tubule transport.
In addition to the systemic renin-angiotensin system, the proximal tubule also contains an autonomous renin-angiotensin system whereby angiotensin II is locally produced and luminally secreted at levels 100-fold greater than in plasma (7, 13, 20, 23, 27, 29, 30). This proximal tubule renin-angiotensin system has been shown to modulate proximal tubule transport independently of systemically circulating angiotensin II (2, 12, 16, 18, 24-26). Inhibition of luminal angiotensin II production within the proximal tubule with administration of luminal enalaprilat decreases proximal tubule volume reabsorption (24). A comparable reduction in proximal tubule volume reabsorption was also observed with luminal administration of losartan, a type 1 angiotensin II (AT1)-receptor antagonist (2, 24). These studies demonstrate that the proximal tubule renin-angiotensin system through luminal angiotensin II can modulate proximal tubule transport independently of systemically circulating angiotensin II.
Unexplored to date, however, is the potential role of the renal nerves to interact with the proximal tubule renin-angiotensin system. The regulation of the renal nerve's effect on proximal tubule transport by the systemic renin-angiotensin system poses an intriguing possibility that a similar interaction between the renal nerves and the proximal tubule renin-angiotensin system might exist. In this study, we examine whether the renal nerves can modulate the effect of proximal tubule luminal angiotensin on volume transport.
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METHODS |
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Preparation of animals. Male Sprague-Dawley rats, weighing between 190 and 250 g, were used for this study. Rat preparation and in vivo microperfusion have been described previously (24, 26). Briefly, all animals were allowed free access to food and water before anesthesia with intraperitoneal inactin (100 mg/kg). Rats were placed on a servo-controlled heated table set to maintain body temperature at 37°C. A tracheostomy was performed, and the jugular vein was cannulated for infusion of normal saline at 2.8 ml/h. A flank incision was then used to expose the left kidney, which was then immobilized in a lucite cup. The kidney was bathed with water-equilibrated mineral oil heated to 37°C that was previously bubbled with 95% O2-5% CO2. The ureter was cannulated with polyethylene tubing (PE-50) to ensure free flow of urine.
In vivo microperfusion. Proximal tubule segments on the surface of the kidney were initially mapped with injection of a small droplet of oil. A wax block was inserted into the lumen of an early proximal tubule loop by a hydraulic Microdrive (Trent Wells, Coulterville, CA), which prevented any glomerular filtrate from flowing into the tubule segments distal to the block. Subsequently, a microperfusion pipette was inserted into the lumen immediately distal to the wax block, and tubules were perfused (30 nl/min) with a microperfusion pump system (K. Effenberger, Vestavia Scientific, Birmingham, AL). Tubules were perfused with an ultrafiltrate-like solution, which was composed of (in mM) 120 NaCl, 25 NaHCO3, 5 KCl, 1 MgSO4, 1.8 CaCl2, 1 Na2HPO4, 5 glucose, 5 alanine, and 5 urea, as well as 0.1% FD & C green dye no. 3. Exhaustively dialyzed [3H]methoxy inulin was added as a volume marker. In a late proximal tubule loop distal to the perfusion pipette an oil block was placed, and a collection pipette was then inserted proximal to the oil block. An average of three tubules were perfused per kidney. Fluid collections were made over a 2- to 3-min period, and the volume was measured by using a constant-bore pipette. Only perfused tubules with an inulin recovery rate of >90 and <110% were included (actual, >90 to <105%). After all collections were performed, the entire tubule was injected with liquid microfil (Flow-Tech, Carver, MA) and allowed to harden overnight. The kidney was later placed in 6 N HCl at 37°C for 1 h. The microfil tubule casts were then dissected and photographed, and the tubular length between the perfusion and collection sites was measured. Microfil dissection and calculation of the rate of volume absorption (Jv) were performed without knowledge of the specific experimental protocol.
Acute and chronic renal denervation. Acute renal denervation was accomplished by the standard mechanicochemical technique after the ureter had been cannulated (3, 31, 32). Briefly, the renal arterial adventitia was stripped, and 10% phenol in absolute ethanol was applied circumferentially around the vessel for 15-20 min. Care was taken to prevent contact of phenol with other surrounding structures. If vasospasm of the renal artery was noted, the animal was not used for the study.
In rats used for the chronic renal denervation studies, denervation of the renal nerves was performed 6-7 days before in vivo microperfusion (31, 32). Using this denervation technique, we demonstrated a 90% reduction in whole kidney norepinephrine content 6 days after surgery [27.2 ± 15.8 vs. 214.7 ± 44.8 pg/mg (contralateral nondenervated kidney), P < 0.005] and [27.2 ± 15.8 vs. 282.7 ± 48.4 pg/mg (sham nondenervated kidney), P < 0.005], respectively. Whole kidney norepinephrine was measured by using a catecholamine research assay system (catecholamines [3H] radioenzymatic assay, Amersham Pharmacia Biotech). Briefly, the kidney was homogenized in 0.4 N perchloric acid, subjected to the enzyme, catechol-O-methyltransferase, and the resulting [3H]methoxy-labeled catecholamine derivative was isolated by thin-layer chromatography and measured by scintillation counting. As a control for the chronically denervated animals, sham animals received a comparable operation except that renal denervation did not take place.Animal protocols.
The role of intraluminally produced angiotensin II on proximal
tubule transport was studied in four groups of animals: control, acutely denervated animals, chronically denervated animals, and sham-operated control animals. Four or more animals were used within
each of the study groups. Proximal tubules were perfused with an
ultrafiltrate-like solution, and the rate of proximal tubule volume
reabsorption was measured. To determine the role of intraluminally
generated angiotensin II on proximal tubule transport, proximal tubule
volume reabsorption was also measured in the presence of
104 M luminal enalaprilat to inhibit intraluminal
angiotensin II production. Luminal 10
4 M enalaprilat has
previously been shown to decrease proximal tubule volume reabsorption
by 40% (24). The difference in volume reabsorption
observed between tubules perfused with and without 10
4 M
enalaprilat is a measure of the contribution of intraluminally generated angiotensin II on proximal tubule transport (2,
24-26). Finally, proximal tubules in acutely and
chronically denervated animals were perfused with an ultrafiltrate-like
solution containing 10
8 M angiotensin II to determine
effect of luminal angiotensin II on proximal tubule transport in
denervated kidneys. The concentration of angiotensin II within the
luminal fluid of the proximal tubule has previously been measured and
found to be 10
8 M (7, 23).
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Calculations and statistical analyses.
The proximal tubule volume reabsorptive rate
(Jv) was calculated in accordance to the
following equation
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RESULTS |
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Effect of chronic renal denervation on the role of intraluminally
generated angiotensin II on proximal tubule volume reabsorption.
In these studies the role of intraluminal angiotensin II on proximal
tubule volume reabsorption was examined in Sprague-Dawley rats 6-7
days after renal denervation or sham operation. Chronic renal
denervation did not significantly reduce the rate of proximal tubule
volume reabsorption compared with the sham control. Proximal tubules
from sham-operated animals had a volume reabsorption rate of 2.70 ± 0.19 nl · mm1 · min
1,
which was significantly greater than 1.60 ± 0.10 nl · mm
1 · min
1 measured in
proximal tubules perfused with an ultrafiltrate-like solution
containing 10
4 M luminal enalaprilat (P < 0.05, Fig. 1). Luminal enalaprilat (10
4 M) has previously been shown to inhibit proximal
tubule volume reabsorption by 40% (24). However, in
chronically denervated tubules the rate of volume reabsorption was
2.26 ± 0.28 nl · mm
1 · min
1, which was
not different from the 2.07 ± 0.20 nl · mm
1 · min
1 measured in
the presence of 10
4 M luminal enalaprilat (Fig.
2).
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Effect of acute renal denervation on intraluminally generated
angiotensin II mediated proximal tubule transport.
We next studied the effect of acute renal denervation on proximal
tubule volume reabsorption. As seen in Fig.
3, the rate of proximal tubule volume
reabsorption was significantly less in proximal tubules from acutely
denervated kidneys than proximal tubules from kidneys with intact
innervation (1.30 ± 0.21 vs. 2.97 ± 0.14 nl · mm1 · min
1,
P < 0.001). In tubules with intact renal innervation,
the rate of volume reabsorption was significantly lower in the presence of 10
4 M luminal enalaprilat (1.61 ± 0.26 nl · mm
1 · min
1) compared
with control innervated tubules perfused with an ultrafiltrate-like solution (2.97 ± 0.14 nl · mm
1 · min
1,
P < 0.001, Fig. 3). This is consistent with our
previous findings that addition of a converting enzyme inhibitor to
decrease intraluminally generated proximal tubule angiotensin II
production reduces the rate of proximal tubule transport (2,
24-26).
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DISCUSSION |
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The renin-angiotensin system and the sympathetic renal nerves play
important roles in the regulation of fluid and solute reabsorption by
the proximal tubule (2-5, 8, 11, 12, 14, 16, 17, 18,
24-26, 28). Recent studies have demonstrated that, in
addition to the systemic renin-angiotensin system, an autonomous
renin-angiotensin system exists within the proximal tubule that can
"locally" synthesize and luminally secrete angiotensin II at levels
100-fold higher than plasma (2, 7, 12, 13, 16, 18, 20,
23-27, 29, 30). The effect of luminal angiotensin II on
proximal tubule volume reabsorption has been controversial (2,
12, 16, 18, 24-26). A rabbit in vitro microperfusion study
demonstrated that addition of 1010 and 10
11
M angiotensin II to the luminal perfusate of the proximal tubule increased volume reabsorption by 142 and 204%, respectively
(16). In contrast, a rat in vivo microperfusion study
demonstrated a much smaller increase of only 20% in proximal tubule
volume reabsorption after administration of luminal 10
11
and 10
12 M luminal angiotensin II, far less than the
effect of systemic angiotensin II on proximal tubule transport
(18). A split droplet study also demonstrated a small 20%
increase in volume reabsorption with 10
9 M luminal
angiotensin II but no effect with 10
11 M angiotensin II
(12). Using in vivo microperfusion in the rat and in vitro
microperfusion in the rabbit, our laboratory has found that addition of
10
6, 10
8, 10
10, and
10
11 M luminal angiotensin II had no effect on proximal
tubule volume reabsorption (2, 24). The small or absent
effect of luminal angiotensin II on proximal tubule volume reabsorption
in the above studies is consistent with existing high levels of luminal
angiotensin II measured in the range of 0.5-4 × 10
8 M (7, 23, 29).
The effect of luminal angiotensin II has also been examined by
inhibiting its production or action in in vivo microperfusion studies.
Addition of losartan, an AT1 angiotensin II-receptor antagonist, to the lumen of the proximal tubule reduced volume reabsorption by 35% (24). A comparable reduction in
volume reabsorption (40%) was also noted with luminal administration
of enalaprilat, an angiotensin-converting enzyme inhibitor
(24). Subsequent addition of 108 M
angiotensin II to the luminal perfusate containing 10
4 M
enalaprilat resulted in an ~82% increase in proximal tubule volume
reabsorption (24). Similar findings have been demonstrated in the rabbit proximal convoluted tubule perfused in vitro
(2). Inhibition of proximal tubule transport by luminal
enalaprilat in in vitro microperfusion is consistent with a direct
tubular effect of luminal angiotensin II, independently of any
confounding systemic factors. These results are consistent with a role
for luminal angiotensin II to modulate proximal tubule transport
independently of systemically circulating angiotensin II (2, 12,
16, 18, 24-26).
The proximal tubule is richly innervated by the sympathetic nervous system (1, 21). With the use of electron microscopy, renal nerve endings have been located adjacent to proximal tubule epithelial cells (1, 21). Acute renal denervation has been shown to decrease absolute proximal tubule water reabsorption in in vivo micropuncture studies (3, 4). These changes in transport occurred in the absence of changes in the glomerular filtration rate or renal blood flow and thus indicate a direct effect of the renal nerves on proximal tubule transport (3, 4). Our present in vivo microperfusion data demonstrate a large decrease in the proximal tubule volume reabsorptive rate after acute renal denervation, consistent with the above micropuncture studies.
Chronic renal denervation did not significantly decrease the proximal
tubule volume reabsorptive rate. These results are at variance with the
results of a previous micropuncture study, which demonstrated that
chronic renal denervation reduced proximal tubule volume reabsorption
(6). Our results were not due to inadequate renal
denervation as there was a 90% decrease in renal norepinephrine content after mechanicochemical renal denervation. Furthermore, the
rate of proximal tubule volume reabsorption was higher after chronic
denervation than after acute denervation. This chronic adaptation in
transport was not the result of an elevated compensatory role of
intraluminal angiotensin II on proximal tubule transport. Inhibition of
intraluminal angiotensin II production with luminal 104 M
enalaprilat in acute and chronically denervated proximal tubules failed
to alter transport, consistent with a small or absent effect for
intraluminal angiotensin II on transport after renal denervation. Clearly, other adaptive responses contributed to the augmented proximal
tubule transport in chronic denervation that were not addressed in this
study (19).
An interaction between the systemic renin-angiotensin system and the sympathetic renal nerves has also been shown in prior studies, whereby the renal nerves require systemically circulating angiotensin II to augment renal sodium transport (11, 14). The mechanism by which circulating angiotensin II influences renal nerve activity is unclear but may involve facilitation of adrenergic transmission at the renal nerve-renal epithelial cell junction (11, 15). The renal nerves may also modulate the proximal tubule renin-angiotensin system. Renal denervation in Balb/c mice reduced the renal renin and renin mRNA content (33). Renal nerve stimulation in Wistar rats increased both renal renin mRNA and angiotensinogen mRNA abundance (22). The rise in renin and angiotensinogen mRNA by renal nerve stimulation were blocked by atenolol (22). Thus the renal nerves may facilitate the production of angiotensin II by augmenting the proximal tubule renin-angiotensin system. In addition to the renal nerves, other independent factors such as alterations in renal perfusion pressure and associated tubuloglomerular feedback interactions might also affect the intraluminal angiotensin II level and proximal tubule transport.
The effect of luminal angiotensin II on proximal tubule transport is
also regulated by changes in the extracellular volume (26). The magnitude of the reduction in proximal tubule
volume reabsorption observed with inhibition of luminal angiotensin II production using 104 M luminal enalaprilat was twofold
greater during acute extracellular volume contraction than during acute
extracellular volume expansion (26). Addition of
10
8 M angiotensin II to the lumen of the proximal tubule
during volume expansion augmented the volume reabsorptive rate twofold
to a rate comparable to that observed during volume contraction
(26). These results are consistent with a role for luminal
angiotensin II in modulating proximal tubule transport during altered
states of extracellular volume (26). However, the
mechanism by which changes in extracellular fluid volume modulate
luminal angiotensin II and its effect on proximal tubule transport are
unclear. It is interesting to speculate that the renal nerves may play
a role in the modulation of the luminal angiotensin II-mediated
component of proximal tubule transport during changes in extracellular
volume. The potential role of the renal nerves to mediate changes in
the effect of luminal angiotensin II on transport resulting from
alterations in extracellular volume is consistent with the renal
nerve's innervation of the proximal tubule and the regulation of its
neural activity by changes in extracellular volume.
In summary, we find that acute and chronic renal denervation abolished
the enalaprilat-sensitive component of proximal tubule volume
transport. The addition of luminal 108 M angiotensin II
augmented proximal tubule volume reabsorption in denervated tubules.
These results are consistent with the renal nerves playing a role in
the modulation of the intraluminally generated angiotensin II component
of proximal tubule transport.
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ACKNOWLEDGEMENTS |
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We acknowledge the excellent secretarial assistance of Janell McQuinn and Laurel Johnson.
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FOOTNOTES |
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Address for reprint requests and other correspondence: A. Quan, Dept. of Pediatrics, Univ. of Texas Southwestern Medical Ctr., 5323 Harry Hines Blvd., Dallas, TX 75235 (E-mail: albert.aquan{at}.utsouthwestern.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 17 April 2000; accepted in final form 21 November 2000.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Barajas, L,
Powers K,
and
Wang P.
Innervation of the renal cortical tubules: a quantitative study.
Am J Physiol Renal Fluid Electrolyte Physiol
247:
F50-F60,
1984
2.
Baum, M,
Quigley R,
and
Quan A.
Effect of luminal angiotensin II on rabbit proximal convoluted tubule bicarbonate absorption.
Am J Physiol Renal Physiol
273:
F595-F600,
1997
3.
Bello-Reuss, E,
Colindres RE,
Pastoriza-Munoz E,
Mueller RA,
and
Gottschalk CW.
Effects of acute unilateral renal denervation in the rat.
J Clin Invest
56:
208-217,
1975[ISI][Medline].
4.
Bello-Reuss, E,
Pastoriza-Muniz E,
and
Colindres RE.
Acute unilateral renal denervation in rats with extracellular volume expansion.
Am J Physiol Renal Fluid Electrolyte Physiol
232:
F26-F32,
1977[ISI][Medline].
5.
Bello-Reuss, E,
Trevino DL,
and
Gottschalk CW.
Effect of renal sympathetic nerve stimulation on proximal water and sodium reabsorption.
J Clin Invest
57:
1104-1107,
1976[ISI][Medline].
6.
Bencsath, P,
Asztalos B,
Szalay L,
and
Takacs L.
Renal handling of sodium after chronic renal sympathectomy in the anesthetized rat.
Am J Physiol Renal Fluid Electrolyte Physiol
236:
F513-F518,
1979[ISI][Medline].
7.
Braam, B,
Mitchell KD,
Fox J,
and
Navar LG.
Proximal tubular secretion of angiotensin II in rats.
Am J Physiol Renal Fluid Electrolyte Physiol
264:
F891-F898,
1993
8.
Cogan, MG.
Angiotensin II: a powerful controller of sodium transport in the early proximal tubule.
Hypertension
15:
451-458,
1990[Abstract].
9.
DiBona, GF.
Neurogenic regulation of renal tubular sodium reabsorption.
Am J Physiol Renal Fluid Electrolyte Physiol
233:
F73-F81,
1977
10.
DiBona, GF.
Neural regulation of renal tubular sodium reabsorption and renin secretion.
Federation Proc
44:
2816-2822,
1985[ISI][Medline].
11.
Handa, RK,
and
Johns EJ.
Interaction of the renin-angiotensin system and the renal nerves in the regulation of rat kidney function.
J Physiol (Lond)
369:
311-321,
1985[Abstract].
12.
Harris, PJ,
and
Young JA.
Dose dependent stimulation and inhibition of proximal tubular sodium reabsorption by angiotensin II in the rat kidney.
Pflügers Arch
367:
295-297,
1977[ISI][Medline].
13.
Ingelfinger, JR,
Zuo WM,
Fon EA,
Ellison KE,
and
Dzau VJ.
In situ hybridization evidence for angiotensinogen messenger RNA in the rat proximal tubule.
J Clin Invest
85:
417-423,
1990[ISI][Medline].
14.
Johns, EJ.
The role of angiotensin II in the antidiuresis and antinatriuresis induced by stimulation of the sympathetic nerves to the rat kidney.
J Auton Pharmacol
7:
205-214,
1987[ISI][Medline].
15.
Johns, EJ.
Editorial review: role of angiotensin II and the sympathetic nervous system in the control of renal function.
J Hypertens
7:
695-701,
1989[ISI][Medline].
16.
Li, L,
Wang YP,
Capparelli AW,
Jo OD,
and
Yanagawa N.
Effect of luminal angiotensin II on proximal tubule fluid transport: role of apical phospholipase A2.
Am J Physiol Renal Fluid Electrolyte Physiol
266:
F202-F209,
1994
17.
Liu, FY,
and
Cogan MG.
Angiotensin II: a potent regulator of acidification in the rat early proximal convoluted tubule.
J Clin Invest
80:
272-275,
1987[ISI][Medline].
18.
Liu, FY,
and
Cogan MG.
Angiotensin II stimulation of hydrogen ion secretion in the rat early proximal tubule: modes of action, mechanism, and kinetics.
J Clin Invest
82:
601-607,
1988[ISI][Medline].
19.
Moe, GW,
Legault L,
and
Skorecki KL.
Extracellular fluid volume and pathophysiology of edema.
In: The Kidney (4th ed.), edited by Brenner BM,
and Rector FC.. Philadelphia, PA: Saunders, 1991, vol. 1, p. 628-643.
20.
Moe, OW,
Kazutomo U,
Star RA,
Miller RT,
Widell J,
Alpern RJ,
and
Henrich WL.
Renin expression in renal proximal tubule.
J Clin Invest
91:
774-779,
1993[ISI][Medline].
21.
Muller, J,
and
Barajas L.
Electron microscopic and histochemical evidence for a tubular innervation in the renal cortex of the monkey.
J Ultrastruct Res
41:
533-549,
1972[ISI][Medline].
22.
Nakamura, A,
and
Johns EJ.
Effect of renal nerves on expression of renin and angiotensinogen genes in rat kidneys.
Am J Physiol Endocrinol Metab
266:
E230-E241,
1994
23.
Navar, LG,
Lewis L,
Hymel A,
Braam B,
and
Mitchell KD.
Tubular fluid concentrations and kidney contents of angiotensins I and II in anesthetized rats.
J Am Soc Nephrol
5:
1153-1158,
1994[Abstract].
24.
Quan, A,
and
Baum M.
Endogenous production of angiotensin II modulates rat proximal tubule transport.
J Clin Invest
97:
2878-2882,
1996
25.
Quan, A,
and
Baum M.
Regulation of proximal tubule transport by angiotensin II.
Semin Nephrol
17:
423-430,
1997[ISI][Medline].
26.
Quan, A,
and
Baum M.
Endogenous angiotensin II modulates rat proximal tubule transport with acute changes in extracellular volume.
Am J Physiol Renal Physiol
275:
F74-F78,
1998
27.
Richoux, JP,
Cordonnier JL,
Bouhnik J,
Clausen E,
Corvol P,
Menard J,
and
Grignon G.
Immunocytochemical localization of angiotensinogen in the rat liver and kidney.
Cell Tissue Res
233:
439-451,
1983[ISI][Medline].
28.
Schuster, VL,
Kokko JP,
and
Jacobson HR.
Angiotensin II directly stimulates sodium transport in rabbit proximal convoluted tubules.
J Clin Invest
73:
507-515,
1984[ISI][Medline].
29.
Seikaly, MG,
Arant BS,
and
Seney FD.
Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat.
J Clin Invest
86:
1352-1357,
1990[ISI][Medline].
30.
Taugner, R,
Hackenthal E,
Rix E,
Nobling R,
and
Poulsen K.
Immunocytochemistry of the renin-angiotensin system: renin, angiotensinogen, angiotensin I, and angiotensin II and converting enzyme in the kidneys of mice, rats, and tree shrews.
Kidney Int
22, Suppl:
S33-S43,
1986.
31.
Thomson, SC,
Tucker BJ,
Gabbai FB,
and
Blantz RC.
Glomerular hemodynamics and 2-adrenoreceptor stimulations: the role of renal nerves.
Am J Physiol Renal Fluid Electrolyte Physiol
258:
F21-F27,
1990
32.
Tucker, BJ,
Mundy CA,
Maciejewski AR,
Printz MP,
Ziegler JG,
Pelayo JC,
and
Blantz RC.
Changes in glomerular hemodynamic response to angiotensin II after subacute renal denervation in rats.
J Clin Invest
78:
680-688,
1986[ISI][Medline].
33.
Yanling, Z,
Morgan T,
and
Read G.
The role of the renal nerves in renin synthesis.
Clin Exp Pharmacol Physiol
19:
827-831,
1992[ISI][Medline].