Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Angiotensin II receptors are present along the rat inner medullary collecting duct (IMCD), although their physiological role is unknown. Because urea is one of the major solutes transported across the terminal IMCD, we measured angiotensin II's effect on urea permeability. In the perfused rat terminal IMCD, angiotensin II had no effect on basal urea permeability but significantly increased vasopressin-stimulated urea permeability by 55%. Angiotensin II, both without and with vasopressin, also increased the amount of 32P incorporated into urea transporter (UT)-A1 in inner medullary tissue exposed to these hormones ex vivo. Because angiotensin II activates protein kinase C, we tested the effect of staurosporine (SSP). In the absence of angiotensin II, SSP had no effect on vasopressin-stimulated urea permeability in the perfused terminal IMCD. However, SSP completely and reversibly blocked the angiotensin II-mediated increase in vasopressin-stimulated urea permeability. SSP and chelerythrine reduced the angiotensin II-stimulated 32P incorporation into UT-A1 in inner medullary tissue exposed ex vivo. We conclude that angiotensin II increases vasopressin-stimulated facilitated urea permeability and 32P incorporation into the 97- and 117-kDa UT-A1 proteins via a protein kinase C-mediated signaling pathway. These data suggest that angiotensin II augments vasopressin-stimulated facilitated urea transport in the rat terminal IMCD and may play a physiological role in the urinary concentrating mechanism by augmenting the maximal response to vasopressin.
inner medullary collecting duct; protein kinase C; urine-concentrating mechanism; phosphorylation; hyperosmolality; urea transporter
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
THE RENIN-ANGIOTENSIN SYSTEM may play an important role in the urinary concentrating mechanism because infusing angiotensin II into the renal artery increases urine osmolality in rats (9), whereas subcutaneous injection of an angiotensin-converting enzyme (ACE) inhibitor for 5 days reduces urine osmolality in mice (27). In addition, knockout of the gene for angiotensinogen, ACE, or angiotensin II receptors impairs urine-concentrating ability (7, 8, 15, 19, 26, 27). In some of these knockout mice (angiotensinogen, ACE), the decrease in urine-concentrating ability results from anatomic abnormalities in the renal medulla. However, mice lacking the type 1A angiotensin II receptor or ACE (ACE.2 mice) have a relatively normal medulla and still have a urine-concentrating defect (8, 27).
The preceding findings suggest that angiotensin II may have a
functional role in nephron segments involved in generating the hypertonic medullary gradient that is needed to concentrate the urine
maximally, i.e., the medullary thick ascending limb (mTAL) and inner
medullary collecting duct (IMCD). Angiotensin II receptors are present
in the mTAL, and angiotensin II stimulates
Na+-K+-2Cl cotransport
(1). Both RT-PCR and in situ hybridization studies show
that the mRNA for angiotensin II receptors is present in the IMCD
(16, 23, 38), and radioligand binding studies show that
angiotensin II receptors are present (24). However, no studies have been performed to determine whether angiotensin II has a
functional role in the IMCD.
Urea is one of the major solutes transported across the terminal IMCD and is important for the generation of the hypertonic medulla needed to concentrate the urine maximally [reviewed in (30)]. In rats consuming a standard diet, the terminal IMCD is the only nephron segment in which vasopressin stimulates facilitated urea transport (18, 33). In the present study, we evaluated whether angiotensin II can regulate urea transport in the terminal IMCD by testing its effect on basal and vasopressin-stimulated facilitated urea permeability. We also tested whether any effects of angiotensin II occurred via protein kinase C (PKC) because angiotensin II can activate it (1, 17, 22).
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Tissue preparation. All animal protocols were approved by the Emory University Institutional Animal Care and Use Committee. Tubules were obtained from pathogen-free male Sprague-Dawley rats (National Cancer Institute, Frederick, MD). Rats were kept in filter-top cages with autoclaved bedding and received free access to water and a standard diet (NIH-31, Ziegler Brothers, Gardner, PA). Kidneys were placed into chilled (17°C), isotonic, dissecting solution to isolate the terminal IMCD (5, 6). The terminal IMCD was identified by dissecting between 50 and 70% of the distance between the inner-outer medullary border (0%) and the papillary tip (100%) as measured by using an eyepiece micrometer (32, 33).
The dissecting solution was gassed with 95% O2-5% CO2 and contained (in mM) 118 NaCl, 25 NaHCO3, 2 CaCl2, 2.5 K2HPO4, 1.2 MgSO4, 5.5 glucose, and 4 creatinine. Tubules were transferred into a bath that was continuously exchanged and bubbled with 95% O2-5% CO2 gas and perfused by using standard techniques (18, 33). Solution and urine osmolalities were measured by vapor pressure osmometry (model 5500, Wescor, Logan, UT).Urea measurement.
The urea concentration in perfusate, bath, and collected fluid was
measured by using a continuous-flow ultramicrofluorometer as described
(18, 32, 33). This assay is capable of resolving differences of 4% or greater in urea concentration (32).
Urea flux (Jurea) was calculated as:
Jurea = CoVo ClVl, where Co is the
urea concentration in perfusate, Cl is the urea
concentration in collected fluid, Vo is the
perfusion rate per unit length of tubule, and Vl
is the collection rate per unit length of tubule.
Phosphorylation of UT-A1. Both inner medullas from a single rat (~50-75 mg) were dissected as previously described (20, 25), cut into small pieces (~5 mg/piece), washed with phosphate (P)-free DMEM, then incubated in P-free DMEM containing 0.1 mCi/ml [32P]orthophosphate for 3 h at 37°C and gassed with 5% CO2. Angiotensin II (100 nM), vasopressin (10 nM), SSP (100 nM), chelerythrine (10 µM), or vehicle was added at the end of the 3-h incubation. Unincorporated 32P was removed from the tissue by six successive washes with P-free DMEM. Tissue was then homogenized in 0.5 ml of isolation buffer (20 mM triethanolamine, 250 mM sucrose, 1 µg/ml leupeptin, and 100 µg/ml phenylmethylsulfonyl fluoride, pH 7.5). An equal volume of radioimmunoprecipitation assay (RIPA) buffer (10 mM Tris, pH 7.4, 2.5 mM EDTA; 50 mM NaF; 1 mM Na4P2O7 · 10H2O; 1% Triton X-100; 10% glycerol; 1% deoxycholate, 1 µg/ml aprotinin, 0.18 mg/ml phenylmethylsulfonyl fluoride, and 0.18 mg/ml orthovanadate) was added to the homogenate, and the sample was sheared with a 26-G needle. Samples were centrifuged to remove insoluble particulates, then incubated overnight with our polyclonal anti-urea transporter (UT)-A1 (25) at 4°C with gentle mixing. Immune complexes were precipitated with protein A agarose (Pierce, Rockford, IL) for 2 h at 4°C, then the pelleted beads were washed seven times with RIPA. Washes were counted to ensure complete removal of unbound radiolabeled material. Laemmli SDS-PAGE sample buffer was added directly to the pellets, samples were boiled for 1 min, and proteins were size-separated on 10% SDS-polyacrylamide gels.
Western blot analysis was performed as previously described (20, 25). Briefly, immunoprecipitated proteins were size-separated by SDS-PAGE on 10% Laemmli gels, electroblotted to polyvinylidene difluoride membranes (Gelman Scientific, Ann Arbor, MI), and incubated for 30 min at room temperature with blocking buffer: 5% nonfat dry milk suspended in Tris-buffered saline (TBS: 20 mM Tris · HCl, 0.5 M NaCl, pH 7.5) (20, 25). The Western blots were incubated with our affinity-purified antibody "C" to rat UT-A1 (20, 25) overnight at 4°C, then washed 3× in TBS-Tween. Blots were then incubated with horseradish peroxidase-linked goat anti-rabbit IgG at a dilution of 1:5,000 (Amersham, Arlington Heights, IL) for 2 h at room temperature, washed 2× with TBS-Tween, and the bound secondary antibody was visualized by using an enhanced chemiluminescence kit (Amersham). Laser densitometry was used to quantitate the enhanced chemiluminescence signal. In all cases, parallel gels were stained with Coomassie blue and showed uniformity of loading (data not shown).Statistics. All data are presented as means ± SE, and n = number of rats. Data from three to four collections were averaged to obtain a single value from each experimental phase in each tubule. To test for statistical significance between two groups, Student's t-test was used. To test more than two groups, an ANOVA was used, followed by Tukey's protected t-test (36) to determine which groups were significantly different. The criterion for statistical significance was P < 0.05.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Effect of angiotensin II.
Adding either 100 pM or 100 nM angiotensin II to the bath had no effect
on basal (no vasopressin) facilitated urea permeability (Fig.
1, solid line). In contrast, either 100 pM or 100 nM angiotensin II significantly increased vasopressin (AVP:10
nM)-stimulated facilitated urea permeability (Fig. 1, dashed line).
|
Phosphorylation of UT-A1.
We divided the inner medullas from two rats (4 inner medullas) into tip
and base samples, incubated them with
[32P]orthophosphate, and immunoprecipitated the UT-A1
proteins to test whether either the 117- or 97-kDa UT-A1 protein was a
phosphoprotein. The Western blot (Fig.
2A) verified that the inner
medullary tip contains both the 117- and 97-kDa glycoprotein forms of
UT-A1 whereas the inner medullary base contains only the 97-kDa isoform (29, 31). Both the 117- and 97-kDa UT-A1 proteins
incorporated 32P (Fig. 2B). To verify that UT-A1
was specifically being immunoprecipitated, the precipitating antibody
was preadsorbed with the immunizing peptide prior to the onset of
immunoprecipitation. Preadsorption of the antibody resulted in greater
than a 90% decrease in immunoprecipitated UT-A1 (Fig. 2C,
left and middle lanes). To confirm that the
precipitated proteins were not the result of a nonspecific association
with the protein A bead system, a parallel inner medullary tissue
sample was incubated with an unrelated polyclonal antibody, rabbit
anti-actin. The Western blot, probed with anti-UT-A1, showed no
recognition of 117- or 97-kDa isoforms in this sample (Fig.
2C, right lane).
|
|
Effect of SSP.
We used the PKC inhibitor SSP to test whether angiotensin II increases
vasopressin-stimulated urea permeability through a PKC-mediated
pathway. SSP (100 nM) had no effect on vasopressin-stimulated facilitated urea permeability but blocked the increase in vasopressin (AVP)-stimulated facilitated urea permeability due to angiotensin II
[AVP: 57 ± 14, AVP + SSP: 66 ± 12, AVP + SSP + angiotensin II (100 pM): 82 ± 11 × 105 cm/s, P = NS, n = 6-10, Fig. 4]. Removing SSP restored the angiotensin II-induced
increase in facilitated urea permeability (AVP + angiotensin II:
183 ± 26 × 10
5 cm/s, P < 0.01 vs. AVP, AVP + SSP, and AVP + SSP + angiotensin II,
n = 4, Fig. 4).
|
|
Hyperosmolality-stimulated facilitated urea transport. Hyperosmolality increases facilitated urea permeability independently of vasopressin in the rat terminal IMCD (10, 34) via an increase in intracellular calcium (11). Because signaling pathways that change intracellular calcium often involve PKC, we used SSP to determine whether PKC may be involved in mediating hyperosmolality's stimulation of facilitated urea transport.
In the presence of vasopressin and SSP, raising perfusate and bath osmolality from 290 to 690 mosmol/kgH2O by adding NaCl significantly increased facilitated urea permeability (290 mosmol/kgH2O: 70 ± 15, 690 mosmol/kgH2O: 109 ± 31 × 10
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The main results in this study are that 1) both the 117- and 97-kDa UT-A1 proteins are phosphoproteins; and 2) angiotensin II increases both vasopressin-stimulated facilitated urea permeability in the rat terminal IMCD and the amount of [32P]orthophosphate incorporated into the 117- and 97-kDa UT-A1 proteins. These results show that angiotensin II does affect tubular transport in the terminal IMCD, presumably by activating angiotensin II receptors present in the IMCD (16, 23, 24, 38) and by increasing the phosphorylation of UT-A1. The angiotensin II-mediated increase in facilitated urea permeability was blocked by SSP, suggesting that angiotensin II increases the maximal response to vasopressin by activating PKC.
Effect of angiotensin II on facilitated urea permeability. In rats fed a standard diet, vasopressin-stimulated facilitated urea transport is present only in the terminal IMCD (33). It plays an important role in the urinary concentrating mechanism by permitting urea to be rapidly transported down its concentration gradient, via the UT-A1 urea transporter protein, to increase urea delivery to the inner medullary interstitium. In the present study, we measured facilitated urea transport by imposing a bath-to-lumen urea gradient across the terminal IMCD. Previous studies showed that perfusing a rat terminal IMCD with a bath-to-lumen or with a lumen-to-bath urea gradient yielded the same value for urea permeability (32). However, we did not measure active (or net) urea transport, i.e., transport of urea in the absence of an imposed urea concentration gradient, in the present study.
When an animal becomes volume depleted, both the renin-angiotensin system and vasopressin release are stimulated in an effort to conserve salt and water and restore blood pressure. Thus the angiotensin II-induced increase in vasopressin-stimulated facilitated urea permeability (present study) could augment urea reabsorption into the deepest portions of the inner medullary interstitium where it is needed to maintain the osmotic gradient and aid in water reabsorption.Role of PKC. Several studies show that angiotensin II modulates tubular transport processes by activating PKC (1, 22, 40). Even in the absence of angiotensin II, PKC inhibits vasopressin-stimulated osmotic water permeability in rabbit cortical collecting ducts (CCDs) (2, 3), whereas inhibiting PKC with SSP results in an increase in both basal- and vasopressin-stimulated osmotic water permeability in the rat IMCD (28).
Although SSP is not completely specific (like most inhibitors), it did not alter vasopressin-stimulated facilitated urea permeability, suggesting that the concentration of SSP we used in this study had no effect on the PKA pathway. Breyer and colleagues (3, 13, 37) used 100 nM SSP to inhibit PKC effects on vasopressin-stimulated osmotic water permeability in the perfused rabbit CCD. The results of the present study suggest that angiotensin II increases vasopressin-stimulated facilitated urea permeability via a PKC-mediated pathway. In Chinese hamster ovary cells, angiotensin II can potentiate vasopressin-dependent cAMP production through the activation of PKC (21). Thus it is possible that the additive effect of angiotensin II on vasopressin-stimulated facilitated urea permeability could be due to an effect of angiotensin II on intracellular cAMP production through activation of PKC. The present studies do not determine whether PKC is acting directly or indirectly through changes in intracellular cAMP. UT-A1 contains consensus phosphorylation sites for both PKC and PKA (35). Thus it is possible that either protein kinase could phosphorylate UT-A1 and increase its activity. The fact that SSP and chelerythrine block the phosphorylation of UT-A1 by angiotensin II suggest that angiotensin II is somehow stimulating the activity of PKC. However, the fact that these PKC inhibitors reduce, but do not eliminate, the basal phosphorylation of UT-A1 suggests that another protein kinase (perhaps PKA) may also be involved in regulating the activity of UT-A1. Future studies will be needed to test this hypothesis. The rat IMCD also expresses a dual angiotensin II/vasopressin receptor that is coupled to adenylyl cyclase (12). This receptor can be stimulated by either angiotensin II or vasopressin (12). Because we observed no effect of angiotensin II on facilitated urea permeability in the absence of vasopressin, it is unlikely that angiotensin II is working through this dual angiotensin II/vasopressin receptor.Role of PKC in hyperosmolality-stimulated facilitated urea permeability. We previously found that hyperosmolality acutely stimulates facilitated urea permeability in the rat terminal IMCD via increases in intracellular calcium but has no effect on cyclic AMP production (11). Increasing osmolality by adding NaCl (or mannitol) increases facilitated urea permeability, even in the absence of vasopressin (34). In addition, hyperosmolality and vasopressin have additive stimulatory effects on facilitated urea permeability, and this stimulation is stable over the time period needed to perform the present studies (10, 34). Thus hyperosmolality is an independent stimulator of facilitated urea transport.
The results of the present study suggest that the effect of hyperosmolality on facilitated urea transport may be mediated, in part, through activation of PKC. Hyperosmolality also activates the mitogen-activated protein kinase cascade in mouse IMCD cells and rat inner medulla (42). Future studies will be needed to confirm and elucidate the role of PKC and other pathways in hyperosmolality's stimulation of urea transport. ![]() |
ACKNOWLEDGEMENTS |
---|
The authors thank Drs. Douglas C. Eaton and William E. Mitch (Emory University) for their critical reading of this manuscript.
![]() |
FOOTNOTES |
---|
This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants R01-DK-41707 and P01-DK-50268.
Portions of this work have been published in abstract form (J Am Soc Nephrol 9: 20A, 1998, Proceedings of the XVth International Congress of Nephrology, Buenos Aires, Argentina, May, 1999, and J Am Soc Nephrol. In press.) and presented at the 31st Annual Meeting of the American Society of Nephrology, October 25-28, 1998, Philadelphia, PA, and the XVth International Congress of Nephrology, May 2-6, 1999, Buenos Aires, Argentina.
Present address of A. Kato: First Department of Medicine, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-3192, Japan.
Address for reprint requests and other correspondence: J. M. Sands, Emory Univ. School of Medicine, Renal Div., WMRB 338, 1639 Pierce Dr., NE, Atlanta, GA 30322 (E-mail: jsands{at}emory.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 3 March 2000; accepted in final form 15 June 2000.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Amlal, H,
Legoff C,
Vernimmen C,
Soleimani M,
Paillard M,
and
Bichara M.
ANG II controls Na+-K+(NH+4)-2Cl cotransport via 20-HETE and PKC in medullary thick ascending limb.
Am J Physiol Cell Physiol
274:
C1047-C1056,
1998
2.
Ando, Y,
Jacobson HR,
and
Breyer MD.
Phorbol myristate acetate, dioctanoylglycerol, and phosphatidic acid inhibit the hydroosmotic effect of vasopressin on rabbit cortical collecting tubule.
J Clin Invest
80:
590-593,
1987[ISI][Medline].
3.
Ando, Y,
Jacobson HR,
and
Breyer MD.
Phosphatidates inhibit vasopressin-induced water transport via protein kinase C activation.
Am J Physiol Renal Fluid Electrolyte Physiol
257:
F524-F530,
1989
4.
Barg, J,
Belcheva MM,
and
Coscia CJ.
Evidence for the implication of phosphoinositol signal transduction in µ-opioid inhibition of DNA synthesis.
J Neurochem
59:
1145-1152,
1992[ISI][Medline].
5.
Clapp, WL,
Madsen KM,
Verlander JW,
and
Tisher CC.
Intercalated cells of the rat inner medullary collecting duct.
Kidney Int
31:
1080-1087,
1987[ISI][Medline].
6.
Clapp, WL,
Madsen KM,
Verlander JW,
and
Tisher CC.
Morphologic heterogeneity along the rat inner medullary collecting duct.
Lab Invest
60:
219-230,
1989[ISI][Medline].
7.
Esther, CR, Jr,
Howard TE,
Marino EM,
Goddard JM,
Capecchi MR,
and
Bernstein KE.
Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility.
Lab Invest
74:
953-965,
1996[ISI][Medline].
8.
Esther, CR, Jr,
Marrero MB,
Howard TE,
Machaud A,
Corvol P,
Capecchi MR,
and
Bernstein KE.
The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice.
J Clin Invest
99:
2375-2385,
1997
9.
Faubert, PF,
Chou SY,
Porush JG,
and
Byrd R.
Regulation of papillary plasma flow by angiotensin II.
Kidney Int
32:
472-478,
1987[ISI][Medline].
10.
Gillin, AG,
and
Sands JM.
Characteristics of osmolarity-stimulated urea transport in the rat IMCD.
Am J Physiol Renal Fluid Electrolyte Physiol
262:
F1061-F1067,
1992
11.
Gillin, AG,
Star RA,
and
Sands JM.
Osmolarity-stimulated urea transport in rat terminal IMCD: role of intracellular calcium.
Am J Physiol Renal Fluid Electrolyte Physiol
265:
F272-F277,
1993
12.
Gonzalez, CB,
Herrera VLM,
and
Ruiz WG.
Renal immunocytochemical distribution and pharmacological properties of the dual angiotensin II/AVP receptor.
Hypertension
29:
957-961,
1997
13.
Hebert, RL,
Jacobson HR,
and
Breyer MD.
PGE2 inhibits AVP-induced water flow in cortical collecting ducts by protein kinase C activation.
Am J Physiol Renal Fluid Electrolyte Physiol
259:
F318-F325,
1990
14.
Herbert, JM,
Augereau JM,
Gleye J,
and
Maffrand JP.
Chelerythrine is a potent and specific inhibitor of protein kinase C.
Biochem Biophys Res Commun
172:
993-999,
1990[ISI][Medline].
15.
Ito, M,
Oliverio MI,
Mannon PJ,
Best CF,
Maeda N,
Smithies O,
and
Coffman TM.
Regulation of blood pressure by the type 1A angiotensin II receptor gene.
Proc Natl Acad Sci USA
92:
3521-3525,
1995[Abstract].
16.
Kakinuma, Y,
Fogo A,
Inagami T,
and
Ichikawa I.
Intrarenal localization of angiotensin II type 1 receptor mRNA in the rat.
Kidney Int
43:
1229-1235,
1993[ISI][Medline].
17.
Karim, Z,
Defontaine N,
Paillard M,
and
Poggioli J.
Protein kinase C isoforms in rat kidney proximal tubule: acute effect of angiotensin II.
Am J Physiol Cell Physiol
269:
C134-C141,
1995
18.
Kato, A,
Naruse M,
Knepper MA,
and
Sands JM.
Long-term regulation of inner medullary collecting duct urea transport in rat.
J Am Soc Nephrol
9:
737-745,
1998[Abstract].
19.
Kihara, M,
Umemura S,
Sumida Y,
Yokoyama N,
Yabana M,
Nyui N,
Tamura K,
Murakami K,
Fukamizu A,
and
Ishii M.
Genetic deficiency of angiotensinogen produces an impaired urine concentrating ability in mice.
Kidney Int
53:
548-555,
1998[ISI][Medline].
20.
Klein, JD,
Price SR,
Bailey JL,
Jacobs JD,
and
Sands JM.
Glucocorticoids mediate a decrease in the AVP-regulated urea transporter in diabetic rat inner medulla.
Am J Physiol Renal Physiol
273:
F949-F953,
1997[ISI][Medline].
21.
Klingler, C,
Ancellin N,
Barrault MB,
Buhler JM,
Elalouf JM,
Clauser E,
Lugnier C,
and
Corman B.
Angiotensin II potentiates vasopressin-dependent cAMP accumulation in CHO transfected cells. Mechanisms of cross-talk between AT1A and V2 receptors.
Cell Signal
10:
65-74,
1998[ISI][Medline].
22.
Liu, FY,
and
Cogan MG.
Role of protein kinase C in proximal bicarbonate reabsorption and angiotensin signaling.
Am J Physiol Renal Fluid Electrolyte Physiol
258:
F927-F933,
1990
23.
Miyata, N,
Park F,
Li XF,
and
Cowley AW, Jr.
Distribution of angiotensin AT1 and AT2 receptor subtypes in the rat kidney.
Am J Physiol Renal Physiol
277:
F437-F446,
1999
24.
Mujais, SK,
Kauffman S,
and
Katz AI.
Angiotensin II binding sites in individual segments of the rat nephron.
J Clin Invest
77:
315-318,
1986[ISI][Medline].
25.
Naruse, M,
Klein JD,
Ashkar ZM,
Jacobs JD,
and
Sands JM.
Glucocorticoids downregulate the rat vasopressin-regulated urea transporter in rat terminal inner medullary collecting ducts.
J Am Soc Nephrol
8:
517-523,
1997[Abstract].
26.
Okubo, S,
Niimura F,
Matsusaka T,
Fogo A,
Hogan BLM,
and
Ichikawa I.
Angiotensinogen gene null-mutant mice lack homeostatic regulation of glomerular filtration and tubular reabsorption.
Kidney Int
53:
617-625,
1998[ISI][Medline].
27.
Oliverio, MI,
Delnomdedieu M,
Best CF,
Li P,
Morris M,
Callahan MF,
Johnson A,
Smithies O,
and
Coffman TM.
Abnormal water metabolism in mice lacking the type 1A receptor for ANG II.
Am J Physiol Renal Physiol
278:
F75-F82,
2000
28.
Rouch, AJ,
and
Kudo LH.
Indomethacin and staurosporine reverse 2 inhibition of water transport in rat IMCD.
Kidney Int
52:
1351-1358,
1997[ISI][Medline].
29.
Rouillard, P,
Klein JD,
Timmer RT,
and
Sands JM.
Glycosylated forms of UT-A urea transporters present in kidney medulla (Abstract).
J Am Soc Nephrol
9:
25A,
1998.
30.
Sands, JM.
Regulation of renal urea transporters.
J Am Soc Nephrol
10:
635-646,
1999
31.
Sands, JM,
Flores FX,
Kato A,
Baum MA,
Brown EM,
Ward DT,
Hebert SC,
and
Harris HW.
Vasopressin-elicited water and urea permeabilities are altered in the inner medullary collecting duct in hypercalcemic rats.
Am J Physiol Renal Physiol
274:
F978-F985,
1998
32.
Sands, JM,
and
Knepper MA.
Urea permeability of mammalian inner medullary collecting duct system and papillary surface epithelium.
J Clin Invest
79:
138-147,
1987[ISI][Medline].
33.
Sands, JM,
Nonoguchi H,
and
Knepper MA.
Vasopressin effects on urea and H2O transport in inner medullary collecting duct subsegments.
Am J Physiol Renal Fluid Electrolyte Physiol
253:
F823-F832,
1987
34.
Sands, JM,
and
Schrader DC.
An independent effect of osmolality on urea transport in rat terminal IMCDs.
J Clin Invest
88:
137-142,
1991[ISI][Medline].
35.
Sands, JM,
Timmer RT,
and
Gunn RB.
Urea transporters in kidney and erythrocytes.
Am J Physiol Renal Physiol
273:
F321-F339,
1997
36.
Snedecor, GW,
and
Cochran WG.
Statistical Methods. Ames, IA: Iowa State Univ. Press, 1980, p. 217-236.
37.
Snyder, HM,
Fredin DM,
and
Breyer MD.
Muscarinic receptor activation inhibits AVP-induced water flow in rabbit cortical collecting ducts.
Am J Physiol Renal Fluid Electrolyte Physiol
260:
F929-F936,
1991
38.
Terada, Y,
Tomita K,
Nonoguchi H,
and
Marumo F.
PCR localization of angiotensin II receptor and angiotensin mRNAs in rat kidney.
Kidney Int
43:
1251-1259,
1993[ISI][Medline].
39.
Tojo, A,
Tisher CC,
and
Madsen KM.
Angiotensin II regulates H+-ATPase activity in rat cortical collecting duct.
Am J Physiol Renal Fluid Electrolyte Physiol
267:
F1045-F1051,
1994
40.
Wang, T,
and
Giebisch G.
Effects of angiotensin II on electrolyte transport in the early and late distal tubule in rat kidney.
Am J Physiol Renal Fluid Electrolyte Physiol
271:
F143-F149,
1996
41.
Weiner, ID,
New AR,
Milton AE,
and
Tisher CC.
Regulation of luminal alkalinization and acidification in the cortical collecting duct by angiotensin II.
Am J Physiol Renal Fluid Electrolyte Physiol
269:
F730-F738,
1995
42.
Wojtaszek, PA,
Heasley LE,
and
Berl T.
In vivo regulation of MAP kinases in Ratus norvegicus renal papilla by water loading and restriction.
J Clin Invest
102:
1874-1881,
1998