(Hypertension. 1999;34:1091-1096.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Defective Dopamine Receptor Function in Proximal Tubules of Obese Zucker Rats
From the Institute for Cardiovascular Studies, College of Pharmacy, University of Houston, Tex.
Correspondence to Tahir Hussain, PhD, Institute for Cardiovascular Studies, College of Pharmacy, University of Houston, Houston TX 77204-5515. E-mail THussain{at}jetson.uh.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Abstract—Some of the pathophysiological consequences of obesity include insulin resistance, increased renal sodium reabsorption, and the development of hypertension. Dopamine promotes renal sodium excretion via activation of D1-like receptors present on the proximal tubules. Reduced dopamine-induced natriuresis and a defect in D1-like receptor function have been reported in the proximal tubules of hypertensive animals. The present study investigated D1-like dopamine receptors and associated G proteins as the initial signaling components in the proximal tubular basolateral membranes of obese Zucker and control lean Zucker rats. We found that the obese rats were hyperinsulinemic, hyperglycemic, and hypertensive compared with the lean rats. Dopamine produced concentration-dependent inhibition of Na,K-ATPase activity in the proximal tubules of lean rats, whereas the inhibitory effect of dopamine was reduced in obese rats. The D1-like receptors measured by [3H]SCH 23390 binding revealed an
45% decrease in Bmax without a change in
Kd in the basolateral membranes of obese
rats compared with lean rats. Although we found an increase in
Gq/11
and no change in Gs in the
basolateral membranes of obese rats, dopamine and SKF 38393 failed to
stimulate G proteins as measured by [35S]GTP
S binding
in obese rats, suggesting a receptor–G protein coupling defect. We
conclude that decrease in D1-like dopamine receptor binding
sites and diminished activation of G proteins, resulting perhaps from
defective coupling, led to the reduced inhibition by dopamine of
Na,K-ATPase activity in the proximal tubules of obese Zucker rats. Such
a defect in renal dopamine receptor function may contribute to sodium
retention and development of hypertension in obese rats.
Key Words: kidney • sodium pump • hypertension, obesity • insulin resistance • obesity
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
More than half of the US population is considered overweight, and nearly one quarter is clinically obese.1 Obesity is a known risk factor for chronic diseases such as heart disease, diabetes, and high blood pressure.2 Efforts have been made to elucidate some of the renal and cardiovascular changes associated with obesity.3 4 5 It has been reported that alterations in sodium homeostasis lead to increased sodium retention in diabetes.6 7 The increased sodium retention is suggested to play an important role in the development of hypertension in diabetic patients.8
The renal dopaminergic system is known to play a significant role in promoting natriuresis and diuresis under various physiological conditions.9 10 In spontaneously hypertensive rats, the natriuretic and diuretic responses to dopamine are reduced in comparison with Wistar-Kyoto rats.11 12 Detailed studies have revealed that a defect exists in the D1-like dopamine receptor–cellular signaling mechanisms present on the renal proximal tubules.13 14 A similar defect in D1-like dopamine receptor-mediated cellular signaling is reported in the proximal tubules of humans with primary hypertension.15 In an attempt to demonstrate a correlation between defective dopamine receptor and hypertension, it has been reported that mice lacking functional D1A receptors (member of the D1-like dopamine receptor) developed hypertension.16 The D1-like dopamine receptors, via Gs and Gq/11 proteins, are linked to the stimulation of adenylyl cyclase and phospholipase C, which lead to the inhibition of the sodium-transporting proteins Na-H exchanger and Na,K-ATPase in the proximal tubules.17 18 19 Because of a defect in D1-like receptor–G protein coupling in the proximal tubules, dopamine and D1-like receptor agonist were unable to stimulate adenylyl cyclase and phospholipase C13 20 and therefore failed to inhibit Na-H exchanger and Na,K-ATPase activities in hypertensive animals.21 22
It is believed that obesity is a primary cause of essential hypertension and type 2 diabetes mellitus or non–insulin-dependent diabetes mellitus.23 It is also known that obesity increases tubular sodium reabsorption, which is suggested to be closely linked to the enhanced activation of antinatriuretic renin-angiotensin and sympathetic systems.4 23 On the other hand, renal production of dopamine is decreased in patients with type 2 diabetes mellitus.24 In addition, exogenously infused dopamine produced markedly lower natriuretic response in insulin-treated patients with type 2 diabetes mellitus.25 On the basis of defective dopamine receptor signaling and reduced natriuretic response to dopamine in hypertension, we hypothesized that a lower natriuretic response to dopamine administration in type 2 diabetes mellitus may be a consequence of defective/reduced dopamine receptor function, leading to an impairment in the D1-like receptor–mediated cellular signaling mechanisms in the proximal tubules. Therefore, in the present study we used obese Zucker rats to measure D1-like receptor and its associated G proteins, which are involved in the inhibition of Na,K-ATPase in the proximal tubules. Obese Zucker rats share many similarities with obese humans who have insulin resistance and type 2 diabetes mellitus and develop hypertension.26
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Male obese and lean Zucker rats (aged 11 to 12 weeks) were purchased from Harlan Sprague-Dawley, Inc (Indianapolis, Ind). The rats were maintained in plastic cages and housed in the animal care facility, where they were fed normal rodent chow and tap water ad libitum.
General Parameters
For blood pressure measurement, the rats were
anesthetized with sodium pentobarbital (50 mg/kg body wt IP).
After a midline incision, the aorta was catheterized below the kidney,
and blood pressure was measured with a Statham pressure transducer and
recorded on a Grass polygraph for 30 minutes. A blood sample was
collected from the aorta in EDTA-coated tubes for measurement of blood
glucose and plasma insulin levels. Blood glucose was measured with a
glucose analyzer (1500 Sidekick, YSI). Plasma insulin was
measured by radioimmunoassay with the use of a kit (Linco Research
Inc).
Isolation and Enrichment of Proximal Tubules
After blood pressure was measured and blood samples were
withdrawn, rats were used for the preparation of renal proximal
tubules.19 Protein was measured with the use of a
kit (Pierce).
Na,K-ATPase Assay
The proximal tubular suspension (1 mg protein per milliliter) in
Krebs’ buffer was incubated without or with dopamine (10 nmol/L
to 1 µmol/L) at 37°C for 20 minutes. After incubation, the
tubules were permeabilized by rapid freezing in dry
ice/acetone and thawing. Na,K-ATPase activity was
measured,19 and activity was expressed as nanomoles
inorganic phosphate per milligram protein per minute.
Membrane Preparation
Rats were anesthetized with pentobarbital (50 mg/kg IP).
After a midline abdominal incision, the kidneys were excised and placed
in ice-cold Tris-buffered saline (pH 7.4), and the outer cortex was
removed above the corticomedullary junction.
Basolateral membranes from the cortices were prepared by the colloidal
suspension of silica (Percoll)/sucrose density gradient
method.27
Receptor-Ligand Binding
Binding of [3H]SCH 23390 to the
basolateral membranes was performed according to the previously
described method.28 To generate saturation isotherm, the
ligand concentration was varied from 1 to 60 nmol/L. Cold SCH 23390
(10 µmol/L) was used for determining the nonspecific
binding.
Western Blot Analysis of Sodium Pump and G
Proteins
The basolateral membrane proteins (25 µg protein in Laemmli
buffer) were separated by SDS–polyacrylamide gel
electrophoresis and then electrophoretically transferred onto immobilon
P membrane (blot). The blot was incubated with the antibodies for
Gq/11 and Gs and
monoclonal antibody for the -subunit of Na pump, followed by
incubation with anti-rabbit or anti-mouse IgG–horseradish peroxidase
conjugate. The signal was detected with the use of chemiluminescent
substrate.
The antibodies for G proteins were polyclonal, purified, and
antipeptides. The amino acid sequence of the peptides, specific to
the respective proteins, was as follows: QLNLKEYNLV C-terminal position
on Gq/11; RMHLRQYELL C-terminal position on
Gs. Specificity of
Gq/11 and Gs protein
antibody was confirmed with the lysates from cultures of bacteria
transformed with cDNA for respective G protein -subunits (performed
by Calbiochem-Novabiochem).
[35S]GTPS Binding Assay
GTP binding assay was performed as earlier
described.29 Briefly, the reaction mixture contained the
following (mmol/L): HEPES 25 (pH 8.0), MgCl2 15,
EDTA 1, dithiothreitol 1, NaCl 100, plus 100 000 cpm
[35S]GTPS, 5 µg membrane protein, and the
agonists. Bound [35S]GTPS was separated from
free by rapid filtration on Whatman GF/C filters. Nonspecific
[35S]GTPS binding was determined in the
presence of 100 µmol/L cold GTPS. The
[35S]GTPS was expressed as nanomoles of
[35S]GTPS bound per milligram protein.
Data Analysis
The values are presented as mean±SE and were subjected
to ANOVA for concentration response curves, followed by the Fisher
protected least significant difference post hoc test and t
test for single concentration responses. P<0.05 was
considered statistically significant.
Chemicals
[35S]GTPS (1200 Ci/mmol) and
[3H]SCH 23390 (81.4 Ci/mmol) were purchased
from DuPont NEN. Dopamine was purchased from Sigma Chemical Co, and SKF
38393 and SCH 23390 were purchased form Research Biochemicals
International. Anti-Gq/11 and
anti-Gs were purchased from
Calbiochem-Novabiochem, and anti- of Na pump was a gift from Dr
Carlos Pedemonte of our department. Other chemicals were from either
Sigma or Fisher Scientific Co.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
General Parameters
The general parameters are given in Figure 1. The obese Zucker rats (598±20 g) were heavier (by
200 g) than the lean rats (393±14 g). The
systolic and diastolic blood pressure readings of
the obese rats (170±4/148± 4 mm Hg) were significantly higher
(P<0.05) than those of the lean rats (129±3/114±3
mm Hg). Blood glucose level in the obese rats was 40% higher
(P<0.05) and levels of plasma insulin were 8 times
greater in the obese rats than in the lean rats. In addition, plasma
renin activity (nanograms angiotensin I per milliliter per
hour) in obese rats (14.14±1.8) was not significantly different than
that in lean rats (18.27±1.16).
|
Effect of Dopamine on Na,K-ATPase Activity in Proximal
Tubules
Dopamine (10 nmol/L to 1 µmol/L) inhibited
Na,K-ATPase activity in the proximal tubules of the lean rats. The
maximal inhibition of 30% was produced by 1 µmol/L dopamine
(Figure 2, top). The inhibition of
Na,K-ATPase activity by dopamine was significantly attenuated in the
proximal tubules of obese rats (Figure 2, top). Na,K-ATPase
control activity (nanomoles per milligram protein per minute) in
lean rats (253±20) was not different from that in obese rats
(275±30). This observation is further supported by Western blot
analysis of the Na pump -subunit (95 kDa) in the
basolateral membranes (Figure 2, bottom). The density of the
-subunit of Na pump in the lean rats was comparable to that in the
obese rats.
|
[3H]SCH 23390 Binding
[3H]SCH 23390 bound in a saturable manner
to the basolateral membranes from both the lean and the obese rats. As
seen in Figure 3, Scatchard
analysis of the data revealed a significant decrease in
receptor number (45%) in the obese rat membranes
(Bmax: 1537±422 fmol per milligram protein
in lean rats and 866±96 fmol per milligram protein in obese rats). The
dissociation constant (Kd) values in lean
(37±11 nmol/L) and obese (35±5 nmol/L) rats were not significantly
different.
|
Effect of Dopamine and SKF 38393 on [35S]GTPS
Binding
As shown in Figure 4, dopamine (0.1
to 100 µmol/L) elicited stimulation of
[35S]GTPS binding in the membranes from lean
rats. However, it failed to stimulate binding in obese rats. Similarly,
SKF 38393 stimulated [35S]GTPS binding in
the membranes of lean rats but failed to stimulate binding in obese
rats. The basal binding of [35S]GTPS in the
membranes of lean (6.06±0.3 pmol/mg protein) and obese (6.44±0.34
pmol/mg protein) rats was not different.
|
Antibody for Gq/11 recognized a single band
(42 kDa), whereas antibody for Gs recognized 2
bands (45 and 48 kDa) in the basolateral membranes subjected to Western
blotting. The densitometric analysis of the bands revealed a
significant increase (48%) in Gq/11 in the
membranes of obese Zucker rats compared with lean rats (Figure 5, top), whereas the densities of
Gs were not different in the basolateral
membranes of obese rats compared with lean rats (Figure 5, bottom).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In this study we investigated D1-like dopamine receptors and coupled G proteins in the proximal tubules of obese and lean Zucker rats. We found a reduced number of D1-like receptor binding sites and reduced stimulation of G proteins by dopamine and SKF 38393 in obese rats compared with lean rats. It is suggested that the reduction in D1-like receptor binding sites and subsequent failure to stimulate G protein led to the reduced inhibition by dopamine of Na,K-ATPase activity in the proximal tubules of obese rats. Whether such a reduction in D1-like receptors, as well as its function in the basolateral membranes of obese Zucker rats, is a generalized phenomenon or specific to the kidney remains to be determined.
Obesity is a metabolic disorder with multiple pathophysiological consequences, including insulin resistance, increased renal sodium reabsorption, and development of hypertension.23 Several investigators have attempted to understand the mechanisms responsible for the development of hypertension in obese individuals as well as in animal models.3 4 5 Obese Zucker rats provide a useful model in which the possible candidate hormones and/or their cellular signaling pathways have been investigated to identify a relationship between the development of hypertension and obesity.4 26 30 In the present study, obese Zucker rats were found to exhibit high plasma insulin levels along with higher blood glucose levels compared with their control lean Zucker rats, suggesting insulin resistance. Moreover, this insulin resistance in obese rats was associated with high blood pressure. Higher levels of plasma insulin and blood glucose found in this study are in agreement with earlier studies.4 30
Endogenously produced kidney dopamine and exogenously
administered dopamine and D1-like agonists
promote sodium excretion, at least in part, via the activation of
D1-like dopamine receptors and subsequent
inhibition of Na-H exchanger and Na,K-ATPase in the proximal
tubules.10 17 19 Numerous reports have suggested a
defective action of dopamine in the proximal tubules of hypertensive
patients and in animal models of hypertension.11 12 13 14 15
Unlike in hypertensive animals and patients in which renal dopamine
production is not affected, patients with type 2 diabetes
mellitus have a reduced renal dopamine
production24 ; the mechanism for this abnormality
is not yet known. However, some studies suggest that increased levels
of plasma insulin may play a role in reducing the production of
renal dopamine,31 perhaps by inhibiting either the
conversion of L-dopa to dopamine or the tubular uptake of
L-dopa. In addition to lower renal dopamine
production, a suppressed natriuretic response to
exogenously infused dopamine has been reported in patients with type 2
diabetes mellitus,25 which would suggest that the dopamine
receptors and/or coupled cellular signaling system may also be
defective in type 2 diabetes mellitus. In the present study we
observed that dopamine-mediated inhibition of Na,K-ATPase activity was
attenuated in the proximal tubules of obese Zucker rats. This suggested
that a defect or downregulation may exist in
D1-like dopamine receptor–mediated
cellular signaling that causes a reduction in dopamine-mediated
inhibition of Na,K-ATPase in the proximal tubules of obese rats. We
measured D1-like receptor binding sites and G
proteins as the initial components of the signaling pathway in the
basolateral membranes from obese and lean Zucker rats to identify the
site(s) of defects that contribute to the reduction in dopamine-induced
inhibition of Na,K-ATPase. It is likely that this phenomenon may
contribute and/or lead to a reduced natriuretic response to
dopamine in obese Zucker rats, as reported in subjects with type 2
diabetes mellitus.25 It should be noted that the reduced
inhibition of Na,K-ATPase by dopamine may not be due to alterations per
se in the number or the activity of Na pumps in obese rats. This was
evident from the finding that there was neither no significant
difference in either the control activity of Na,K-ATPase or the
quantity of -subunit, the sodium-transporting part of the enzyme, as
measured by Western blotting between obese and lean rats.
The binding of [3H]SCH 23390 revealed that the
number of D1-like dopamine receptor binding sites
was reduced by 45% in the basolateral membranes of obese rats
without a change in affinity (Kd) to the
ligand. We earlier reported a similar reduction in
D1-like receptor binding sites in the proximal
tubules of old Fischer 344 rats compared with adult
rats.28 However, Fischer 344 rats were not
hypertensive.28 It is not known whether the reduction in
D1-like receptor binding sites is due to a
decrease in the synthesis of receptors or internalization and
degradation of receptors. The decrease in D1-like
receptor binding sites may be partly responsible in the attenuation of
dopamine-mediated inhibition of Na,K-ATPase in the proximal tubules of
obese Zucker rats.
Quantification of Gq/11 and
Gs proteins and agonist-induced activation of G
proteins were performed to assess the next component of the
D1-like receptor signaling pathway. Western blot
analysis of the basolateral membranes revealed an increase in
the -subunit of Gq/11 protein and no change in
the -subunit of Gs protein in obese rats
compared with lean rats. However, while dopamine and SKF 38393 caused a
concentration-dependent activation of G proteins (as measured by
[35S]GTPS binding) in lean rats, this
response was absent in obese rats. We reported a similar defect in G
protein activation by dopamine in the basolateral membranes of old
Fischer 344 rats in which D1-like receptors were
reduced and the levels of G proteins were increased.28 A
45% reduction in D1-like dopamine receptors may
not account for the total failure of dopamine and SKF 38393 to
stimulate G proteins, as measured by
[35S]GTPS binding, in obese rats. It
is possible that G proteins in obese rats may be defective and/or may
not be available for interacting with D1-like
receptors. In experiments conducted in spontaneously hypertensive rats,
it was discovered that D1-like dopamine receptor
numbers were not altered,13 but the activation of G
proteins29 and the subsequent stimulation of second
messengers were significantly reduced compared with Wistar-Kyoto
rats.13 20 The D1-like receptors
were unable to bind to the agonist with high affinity because of a
defect in a receptor–G protein coupling.13 A recent study
in the proximal tubules of essential hypertensive subjects suggested
that agonist-independent phosphorylation of
D1 dopamine receptors may be the molecular cause
of the defect in the receptor–G protein coupling.15 It is
yet to be determined whether a similar mechanism of receptor–G protein
uncoupling exists in the proximal tubules of obese rats. However, the
failure of dopamine and SKF 38393 to activate G proteins
suggests that there may be little or no stimulation to these agonists
of the effector enzymes (phospholipase C and adenylyl cyclase)
in the proximal tubules of obese Zucker rats.
The mechanism(s) responsible for reduced D1-like dopamine receptor function in the proximal tubules of obese Zucker rats is not known. However, it is possible that the reduction in D1-like dopamine receptor binding sites and a defect in coupling with the G proteins may be 2 different independent phenomena. It is known that the defect in D1-like receptor–G protein coupling in the proximal tubules of spontaneously hypertensive rats exists even before the development of hypertension,32 when such defect is proposed to have contributed to the development of hypertension. The obese Zucker rats used in this study are hypertensive. Furthermore, it is also important to determine in future studies whether the defective dopamine receptor function is related to hypertension, obesity, or insulin-resistant phenotype in these animals. Younger obese Zucker rats aged 3 to 4 and 7 to 8 weeks may be used to delineate the mechanisms of such a receptor defect when these animals have not yet developed hypertension, obesity, and insulin resistance.
In summary, we found that obese Zucker rats were hypertensive and displayed higher levels of plasma insulin and blood glucose. The D1-like dopamine receptor binding sites were reduced and the activation of G proteins by dopamine and D1-like agonists was diminished, which may account for the reduced inhibition of Na,K-ATPase by dopamine in the proximal tubules of obese rats. This is the first demonstration of such a defect in the ability of dopamine to inhibit Na,K-ATPase, which may contribute to increased sodium reabsorption and development of hypertension in obese Zucker rats.
Received March 9, 1999; first decision April 6, 1999; accepted June 29, 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
-
Wickelgren I. Obesity: how big a problem?
Science. 1998;280:1364–1367.
[Free Full Text] - Berg FM, ed. Special report: health risks of obesity. Obesity and Health. 2nd ed. Hettinger, NC: Healthy Living Institute; 1993.
- Wood JE, Cash JR. Obesity and hypertension: clinical and experimental observations. Ann Intern Med. 1939;13:922–928.
-
Hall JE, Branda MW, Dixon WN, Smith MJ.
Obesity-induced hypertension: renal function and systemic
hemodynamics. Hypertension. 1993;22:292–299.
[Abstract/Free Full Text] -
Alonso-Galicia M, Brands MW, Zappe DH, Hall JE.
Hypertension in obese Zucker rats: role of angiotensin II
and adrenergic activity. Hypertension. 1996;28:1047–1054.
[Abstract/Free Full Text] - O’Hare JP, Roland JM, Walters G, Corall RJM. Impaired sodium retention in response to volume expansion induced by water immersion in insulin-dependent diabetes mellitus. Diabetes Res. 1986;3:213–215.[Medline] [Order article via Infotrieve]
- deChatel R, Wiedmann P, Flammer J, Zeigler WH, Beretta-Piccoli C, Vetter W, Reubi FC. Sodium, renin, aldosterone, catecholamines and blood pressure in diabetes mellitus. Kidney Int. 1977;12:412–421.[Medline] [Order article via Infotrieve]
- Feldt-Rasmussen B, Mathiesen ER, Deckert T, Geise J, Christersen NJ, Bent-Hansen L, Nielsen MD. Central role for sodium in the pathogenesis of blood pressure changes independent of angiotensin, aldosterone and catecholamines in type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1987;30:610–617.[Medline] [Order article via Infotrieve]
- Lee MR. Dopamine and the kidney. Clin Sci. 1982;312:77–83.
-
Hegde SS, Jadhav AL, Lokhandwala MF. Role of kidney
dopamine in the natriuretic response to volume expansion in
rats. Hypertension. 1989;13:828–834.
[Abstract/Free Full Text] -
Felder RA, Seikaly MG, Cody P, Eisner GM, Jose PA.
Attenuated renal response to dopaminergic drugs in spontaneously
hypertensive rats. Hypertension. 1990;15:560–569.
[Abstract/Free Full Text] - Chen CJ, Lokhandwala MF. An impairment of tubular DA-1 receptor function as a causative factor for diminished natriuresis to volume expansion in spontaneously hypertensive rats. Clin Exp Hypertens. 1992;14:615–628.
- Kinoshita S, Sidhu A, Felder RA. Defective dopamine-1 receptor adenylate cyclase coupling in the proximal convoluted tubules from the spontaneously hypertensive rats. J Clin Invest. 1989;84:1849–1858.
-
Ohbu K, Felder RA. Nephron specificity of dopamine
receptor-adenylyl cyclase defect in spontaneous hypertension.
Am J Physiol. 1993;264:F274–F279.
[Abstract/Free Full Text] - Sanada H, Jose PA, Yu PY, Hazen-Martin D, Carey RM, Bruns D, Felder RA. Human hypertensive subjects have a renal proximal tubular defect in dopamine-1 receptor/adenylyl cyclase coupling. J Am Soc Nephrol. 1997;8:307A. Abstract.
- Albrecht FE, Draog J, Felder RA, Printz MP, Eisner GM, Robillard JE, Sibley DR, Westphal HJ, Jose PA. Role of D1A dopamine receptor in the pathogenesis of genetic hypertension. J Clin Invest. 1996;97:2283–2288.[Medline] [Order article via Infotrieve]
-
Felder CC, Campbell T, Albrecht F, Jose PA. Dopamine
inhibits Na+-H+-exchanger
activity in renal BBMV by stimulation of adenylate cyclase.
Am J Physiol. 1990;259:F297–F303.
[Abstract/Free Full Text] -
Vyas SJ, Eichberg J, Lokhandwala MF. Characterization
of receptors involved in dopamine induced activation of phospholipase-C
in rat renal cortex. J Pharmacol Exp Ther.. 1992;260:134–139.
[Abstract/Free Full Text] - Chen CJ, Lokhandwala MF. Inhibition of Na+,K+-ATPase in rat renal proximal tubules by dopamine involved D1-like dopamine receptor activation. Naunyn Schmiedebergs Arch Pharmacol. 1993;347:289–295.[Medline] [Order article via Infotrieve]
-
Chen CJ, Vyas SJ, Eichberg J, Lokhandwala MF.
Diminished phospholipase C activation by dopamine in spontaneously
hypertensive rats. Hypertension. 1992;19:102–108.
[Abstract/Free Full Text] -
Gesek FA, Schoolwerth AC. Hormone response to proximal
Na, H-exchanger in spontaneously hypertensive rats. Am J
Physiol. 1991;261:F526–F536.
[Abstract/Free Full Text] -
Chen CJ, Beach RE, Lokhandwala MF. Dopamine fails to
inhibit renal tubular sodium pump in hypertensive rats.
Hypertension. 1993;21:364–372.
[Abstract/Free Full Text] - Hall JE, Brandts MW, Henegar JR, Shek EW. Abnormal kidney function as a cause and a consequence of obesity hypertension. Clin Exp Pharmacol Physiol. 1998;25:58–64.[Medline] [Order article via Infotrieve]
- Chan JCN, Critchley JH, Ho CS, Nicholls MG, Cockram CS, Swaminathan R. Atrial natriuretic peptide and urinary dopamine output in non-insulin-dependent diabetes mellitus. Clin Sci. 1992;83:247–253.[Medline] [Order article via Infotrieve]
- Segers O, Anckaert E, Gerlo E, Dupont AG, Somers G. Dopamine-sodium relationship in type 2 diabetic patients. Diabetes Res Clin Pract. 1996;34:89–98.[Medline] [Order article via Infotrieve]
-
Kurtz TW, Morris RC, Pershadsingh HA. The Zucker fatty
rat as a genetic model of obesity and hypertension.
Hypertension. 1989;13:896–901.
[Abstract/Free Full Text] - Sacktor BL, Rosenbloom IL, Liang CT, Cheng L. Na-gradient and sodium plus potassium gradient-dependent glutamate uptake in renal basolateral membrane vesicles. J Membr Biol. 1981;60:63–71.[Medline] [Order article via Infotrieve]
-
Kansra V, Hussain T, Lokhandwala MF. Alterations in
dopamine DA1 receptor and G proteins in renal proximal tubules of old
rats. Am J Physiol. 1997;273:F53–F59.
[Abstract/Free Full Text] -
Hussain T, Lokhandwala MF. Renal dopamine-1 receptor
coupling with Gs and Gq/11 proteins in spontaneously hypertensive rats.
Am J Physiol. 1997;272:F339–F346.
[Abstract/Free Full Text] -
Zeigler DW, Patel KP. Reduced renal responses to an
acute saline load in obese Zucker rats. Am J Physiol. 1991;261:R712–R718.
[Abstract/Free Full Text] - Segers O, Dupont AG, Gerlo E, Somers G. Urinary sodium and dopamine excretion, II: role of hyperinsulinemia in renal dopamine production. Med Sci. 1996;24:571–572.
-
Felder RA, Kinoshita S, Ohbu K, Mouradian MM, Sibley
DR, Monsma FJ Jr, Minowa T, Minowa MT, Canessa LM, Jose PA. Organ
specificity of the dopamine receptor/adenylyl cyclase coupling defect
in spontaneously hypertensive rats. Am J Physiol. 1993;264:R726–R732.
[Abstract/Free Full Text]
This article has been cited by other articles:
 |
|
 |
|
  S. Tiwari, S. Riazi, and C. A. Ecelbarger Insulin's impact on renal sodium transport and blood pressure in health, obesity, and diabetes Am J Physiol Renal Physiol, October 1, 2007; 293(4): F974 - F984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Z. Fardoun, M. Asghar, and M. Lokhandwala Role of oxidative stress in defective renal dopamine D1 receptor-G protein coupling and function in old Fischer 344 rats Am J Physiol Renal Physiol, November 1, 2006; 291(5): F945 - F951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Marwaha and M. F. Lokhandwala Tempol reduces oxidative stress and restores renal dopamine D1-like receptor- G protein coupling and function in hyperglycemic rats Am J Physiol Renal Physiol, July 1, 2006; 291(1): F58 - F66. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Hakam and T. Hussain Angiotensin II AT2 receptors inhibit proximal tubular Na+-K+-ATPase activity via a NO/cGMP-dependent pathway Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1430 - F1436. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Hakam and T. Hussain Angiotensin II Type 2 Receptor Agonist Directly Inhibits Proximal Tubule Sodium Pump Activity in Obese But Not in Lean Zucker Rats Hypertension, June 1, 2006; 47(6): 1117 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Trivedi and M. F. Lokhandwala Rosiglitazone restores renal D1A receptor-Gs protein coupling by reducing receptor hyperphosphorylation in obese rats Am J Physiol Renal Physiol, August 1, 2005; 289(2): F298 - F304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Banday, T. Hussain, and M. F. Lokhandwala Renal dopamine D1 receptor dysfunction is acquired and not inherited in obese Zucker rats Am J Physiol Renal Physiol, July 1, 2004; 287(1): F109 - F116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Marwaha, A. A. Banday, and M. F. Lokhandwala Reduced renal dopamine D1 receptor function in streptozotocin-induced diabetic rats Am J Physiol Renal Physiol, March 1, 2004; 286(3): F451 - F457. [Abstract] [Full Text]
|
|
|
|
|
|
M. Trivedi, A. Marwaha, and M. Lokhandwala Rosiglitazone Restores G-Protein Coupling, Recruitment, and Function of Renal Dopamine D1A Receptor in Obese Zucker Rats Hypertension, February 1, 2004; 43(2): 376 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Banday, M. Asghar, T. Hussain, and M. F. Lokhandwala Dopamine-Mediated Inhibition of Renal Na,K-ATPase Is Reduced by Insulin Hypertension, June 1, 2003; 41(6): 1353 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. N. Umrani, A. A. Banday, T. Hussain, and M. F. Lokhandwala Rosiglitazone Treatment Restores Renal Dopamine Receptor Function in Obese Zucker Rats Hypertension, December 1, 2002; 40(6): 880 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Bickel, J. G. Verbalis, M. A. Knepper, and C. A. Ecelbarger Increased renal Na-K-ATPase, NCC, and beta -ENaC abundance in obese Zucker rats Am J Physiol Renal Physiol, October 1, 2001; 281(4): F639 - F648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sato, M. Soma, T. Nakayama, and K. Kanmatsuse Dopamine D1 Receptor Gene Polymorphism Is Associated With Essential Hypertension Hypertension, August 1, 2000; 36(2): 183 - 186. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||