Reduced renal responses to an acute saline load in obese Zucker rats

1991 ◽  
Vol 261 (3) ◽  
pp. R712-R718 ◽  
Author(s):  
D. W. Zeigler ◽  
K. P. Patel
Keyword(s):  
Blood Pressure ◽  
Sodium Excretion ◽  
Volume Expansion ◽  
Urine Flow ◽  
Reflex Response ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats ◽  
Renal Responses

The purpose of this study was to determine if the reflex response to a saline load is altered in the obese Zucker rat. The obese Zucker rat is a genetic model of obesity and insulin-resistant diabetes that has been reported to have high blood pressure. We examined the reflux renal responses to volume expansion in both anesthetized obese and lean Zucker rats. Initial blood pressure was significantly elevated in the obese Zucker rats compared with the lean controls. Urine flow and sodium excretion from innervated and denervated kidneys were measured before and after volume expansion with normal saline. Volume expansion resulted in significantly less urine flow and sodium excretion in the obese than the lean Zucker rats. This response was evident in both the intact and denervated kidneys. Rats were then infused with atrial natriuretic peptide (ANP) to determine if natriuretic and diuretic responses were altered in these rats. The diuretic action of ANP was not significantly reduced in the obese Zucker rat. However, the natriuretic action of ANP was significantly attenuated in the obese rats. These results indicate that the reflux response to an acute saline load is attenuated in the obese Zucker rat and that this decreased response may be due to a reduction in the direct action of ANP on the kidney.

scholarly journals The age-related increase in renal clusterin mRNA is accelerated in obese Zucker rats.

1998 ◽  
Vol 9 (1) ◽  
pp. 38-45 ◽  
Author(s):  
N J Laping ◽  
B A Olson ◽  
J R Day ◽  
B M Brickson ◽  
L C Contino ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tissue Injury ◽  
Rat Kidney ◽  
Zucker Rats ◽  
Mrna Levels ◽  
Zucker Rat ◽  
Age Related ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats ◽  
F344 Rats

Clusterin is a multifunctional glycoprotein associated with development and tissue injury. Because renal function decreases with advancing age in the obese Zucker rat, clusterin mRNA expression was examined in the kidney of young adult Zucker rats and compared with age-related changes in renal clusterin mRNA expression in Fischer 344 (F344) rats. Renal clusterin mRNA levels in the obese Zucker rat were 2.5-fold higher by 3 mo of age and fourfold higher at 5 mo of age compared with the lean strain. In comparison, renal clusterin mRNA in 12-mo-old F344 rats was twofold higher than in 3-mo-old animals and was tenfold higher at 24 mo of age. Clusterin mRNA was positively correlated with urinary protein excretion and negatively correlated with creatinine clearance in Zucker rats. Clusterin was increased in select nephrons of the obese Zucker rat kidney and in 24-mo-old F344 rat kidney as assessed by in situ hybridization. Increased expression of clusterin mRNA occurred mostly in the tubular epithelium of dilated, convoluted proximal tubules. These data indicate that renal clusterin mRNA levels increase as a function of age and that age-related increases in renal clusterin and the associated tubular abnormalities are accelerated in obese Zucker rats.

scholarly journals Mechanism controlling sleep organization of the obese Zucker rats

1998 ◽  
Vol 84 (1) ◽  
pp. 253-256 ◽  
Author(s):  
David Megirian ◽  
Jacek Dmochowski ◽  
Gaspar A. Farkas
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Zucker Rats ◽  
Rapid Eye Movement ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
The Mean

Megirian, David, Jacek Dmochowski, and Gaspar A. Farkas. Mechanism controlling sleep organization of the obese Zucker rat. J. Appl. Physiol. 84(1): 253–256, 1998.—We tested the hypothesis that the obese ( fa/fa) Zucker rat has a sleep organization that differs from that of lean Zucker rats. We used the polygraphic technique to identify and to quantify the distribution of the three main states of the rat: wakefulness (W), non-rapid-eye-movement (NREM), and rapid-eye-movement (REM) sleep states. Assessment of states was made with light present (1000–1600), at the rats thermoneutral temperature of 29°C. Obese rats, compared with lean ones, did not show significant differences in the total time spent in the three main states. Whereas the mean durations of W and REM states did not differ statistically, that of NREM did ( P = 0.046). However, in the obese rats, the frequencies of switching from NREM sleep to W, which increased, and from NREM to REM sleep, which decreased, were statistically significantly different ( P = 0.019). Frequency of switching from either REM or W state was not significantly different. We conclude that sleep organization differs between lean and obese Zucker rats and that it is due to a disparity in switching from NREM sleep to either W or REM sleep and the mean duration of NREM sleep.

scholarly journals Adipsin mRNA amounts are not decreased in the genetically obese Zucker rat

1989 ◽  
Vol 257 (3) ◽  
pp. 917-919 ◽  
Author(s):  
I Dugail ◽  
X Le Liepvre ◽  
A Quignard-Boulangé ◽  
J Pairault ◽  
M Lavau
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Obese Mice ◽  
High Fat ◽  
Adult Rats ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Obese Zucker Rats

Adipsin gene expression as assessed by mRNA amounts was examined in adipose tissue of genetically obese rats at the onset (16 days of age) or at later stages (30 and 60 days of age) of obesity. Amounts of mRNA were equivalent in obese and lean rats at 16 days of age. In adult rats, we observed a 2-fold decrease in adipsin mRNA in the obese rats compared with control lean rats, which was abolished by weaning the animals on a high-fat diet. Our data show that, in sharp contrast with genetically obese mice, adipsin mRNA is not suppressed in genetically obese Zucker rats.

Hemodynamic and renal responses to volume expansion in dogs with cardiac denervation

1988 ◽  
Vol 254 (6) ◽  
pp. F780-F786
Author(s):  
R. Pichet ◽  
J. Gutkowska ◽  
M. Cantin ◽  
M. Lavallee
Keyword(s):  
Plasma Levels ◽  
Sodium Excretion ◽  
Atrial Natriuretic Factor ◽  
Volume Expansion ◽  
Urine Flow ◽  
Conscious Dogs ◽  
Base Line ◽  
Aortic Constriction ◽  
Cardiac Denervation ◽  
Renal Responses

Hemodynamic responses, renal function, and plasma levels of immunoreactive atrial natriuretic factor (irANF) were examined following volume expansion (VE) in normal (N) conscious dogs and in conscious dogs with cardiac denervation (CD). Base-line urine flow was consistently greater (P less than 0.05) in dogs with CD (0.54 +/- 0.06 ml/min) than in N (0.29 +/- 0.03 ml/min) dogs but sodium excretion did not differ between N (2.80 +/- 0.58 mu eq.min-1.kg body wt-1) and CD (3.53 +/- 0.75 mu eq.min-1.kg-1) groups. With VE (18 ml/kg of 3% dextran in saline), mean arterial pressure (MAP) increased (P less than 0.01) by 16 +/- 3 from 103 +/- 4 mmHg in N dogs but did not change from pre-VE base line (103 +/- 2 mmHg) in dogs with CD. At 10 min after VE, urine flow increased more (P less than 0.01) in N dogs (1.39 +/- 0.24 ml/min) than in dogs with CD (0.26 +/- 0.09 ml/min). At that time, increases in sodium excretion were also greater (P less than 0.01) in N (9.13 +/- 1.96 mu eq.min-1.kg-1) dogs than in dogs with CD (1.06 +/- 0.68 mu eq.min-1.kg-1). With VE, increases in irANF plasma levels were not different in N dogs (40 +/- 12 from 34 +/- 5 pg/ml) and in dogs with CD (27 +/- 3 from 45 +/- 7 pg/ml). In dogs with CD, when MAP was increased by aortic constriction to mimic responses observed in N dogs, renal responses were similar to those of N dogs.(ABSTRACT TRUNCATEDAT 250 WORDS)

Pyruvate carboxylase in genetic obesity

1992 ◽  
Vol 262 (5) ◽  
pp. E608-E618 ◽  
Author(s):  
C. J. Lynch ◽  
K. M. McCall ◽  
M. L. Billingsley ◽  
L. M. Bohlen ◽  
S. P. Hreniuk ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Pyruvate Carboxylase ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Rat Adipocytes ◽  
Obese Zucker Rat ◽  
Streptozotocin Induced Diabetes ◽  
Obese Zucker Rats ◽  
Relative Molecular Weight ◽  
Polyclonal Antisera

Immunoblotting and protein microsequencing were used to identify several adipocyte proteins expressed in an obesity-related fashion in the Zucker rat. One of these was a 116-kDa particulate protein (p116). The p116 levels in adipocytes from 5- to 7-wk-old obese Zucker rats were two- to fivefold higher on a per milligram of protein basis than levels in lean animals and decreased after the induction of streptozotocin-induced diabetes mellitus. This suggests the change may be related to the actions of insulin. Hepatic levels of p116 did not change. The p116 was purified to homogeneity from obese Zucker rat adipocytes, and polyclonal antisera were prepared against the purified protein in rabbits. Microanalysis of electroblotted p116 proteolytic fragments suggested that p116 was pyruvate carboxylase (PC). Other evidence that p116 was PC included the following: 1) p116 contained biotin, 2) p116 in particulate subcellular fractions was soluble after freeze-lysis, 3) antibodies to p116 reacted with purified hepatic PC, 4) p116 and purified hepatic PC had identical pI and relative molecular weight values, and 5) similar changes were detected in adipocyte p116 and PC enzyme activity during obesity and after the induction of streptozotocin-induced diabetes mellitus. Increased adipose tissue PC probably contributes to the increased lipogenic capacity of young obese Zucker rat adipocytes.

scholarly journals 2060 Exploring gene expression signature shared between obese Zucker rat and human cardiac hypertrophy

2018 ◽  
Vol 2 (S1) ◽  
pp. 11-11
Author(s):  
Mackenzie Newman ◽  
Janelle Stricker ◽  
Han-Gang Yu
Keyword(s):  
Cardiac Hypertrophy ◽  
Drug Target ◽  
Model Organism ◽  
Gene Expression Signature ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Future Directions ◽  
Obese Zucker Rat ◽  
Study Population ◽  
Obese Zucker Rats

OBJECTIVES/SPECIFIC AIMS: Objectives: To determine genes that are shared between human and obese Zucker rat hypertrophic hearts, in order to identify potential early biomarkers and drug target for heart failure. METHODS/STUDY POPULATION: Four age-paired lean and obese Zucker rats were used. The human data are derived from doi:10.1152/physiolgenomics.00122.2016. RESULTS/ANTICIPATED RESULTS: We expect to find genes that are upregulated and downregulated in Zucker rats and humans that present cardiac hypertrophy. DISCUSSION/SIGNIFICANCE OF IMPACT: The genes and proteins determined from this study will provide future directions in order to determine whether obese Zucker rats are a valid model organism for the development of cardiac hypertrophy.

Nitric oxide and renal effects of volume expansion in conscious monkeys

1997 ◽  
Vol 272 (4) ◽  
pp. R1033-R1038 ◽  
Author(s):  
T. V. Peterson ◽  
A. B. Carter ◽  
R. A. Miller
Keyword(s):  
Nitric Oxide ◽  
Sodium Excretion ◽  
Volume Expansion ◽  
Control Volume ◽  
No Synthase ◽  
Urine Flow ◽  
Primate Species ◽  
Constant Infusion ◽  
Synthase Inhibitor ◽  
Renal Responses

Experiments were performed to determine the effects of nitric oxide (NO) synthase inhibition on the renal responses to volume expansion in conscious cynomolgus monkeys. All animals were volume expanded with 3% dextran in normal saline under three conditions: 1) during a control state, 2) during constant infusion of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 30 microg x kg(-1) x min(-1)), and 3) during simultaneous infusion of L-NAME and excess NO substrate L-arginine (0.6 mg x kg(-1) x min(-1)). The control volume expansion increased urine flow from 0.27 +/- 0.05 to 0.94 +/- 0.28 ml/min and sodium excretion from 21 +/- 9 to 95 +/- 26 microeq/min. During L-NAME infusion, these responses were attenuated in that urine flow only increased from 0.13 +/- 0.03 to 0.28 +/- 0.09 ml/min and sodium excretion from 13 +/- 8 to 35 +/- 23 microeq/min. Addition of L-arginine to the L-NAME infusion abolished these renal excretory effects of L-NAME alone. With combined L-NAME/L-arginine, volume expansion increased urine flow from 0.37 +/- 0.23 to 1.09 +/- 0.23 ml/min and sodium excretion from 38 +/- 27 to 150 +/- 24 microeq/min, responses similar to control. L-Arginine also markedly attenuated the effect of L-NAME to increase mean arterial pressure and abolished the L-NAME decreases in creatinine and p-aminohippurate clearances. However, an L-NAME-induced bradycardia could only be partially reversed. These results demonstrate that a functioning NO system may be important in mediating normal renal responses to volume expansion in this primate species.

Pentobarbital potentiates natriuretic response to acute volume expansion in monkeys

1988 ◽  
Vol 254 (5) ◽  
pp. R727-R729
Author(s):  
J. P. Gilmore ◽  
K. G. Cornish ◽  
M. W. Barazanji
Keyword(s):  
Sodium Excretion ◽  
Volume Expansion ◽  
Urine Flow ◽  
Inhibitory Influence ◽  
Lower Blood Pressure ◽  
Lower Blood ◽  
Renal Tubular ◽  
Renal Responses ◽  
Conscious Animals ◽  
Dextran Solution

We determined the influence of pentobarbital sodium on the renal responses of the monkey to acute intravascular volume expansion. Before volume expansion, the anesthetized animals had a significantly lower blood pressure and creatinine clearance and a significantly higher urine flow and sodium excretion than the conscious animals. After volume expansion with an isotonic, isoncotic, dextran solution, sodium excretion and urine flow increased significantly in both groups of animals. However, both responses were significantly greater in the anesthetized animals. The greater natriuresis in the anesthetized animals was associated with a greater fractional sodium excretion than in the conscious animals. The potentiated response of the anesthetized animal may be the result of a direct renal tubular effect of pentobarbital and/or the result of the anesthetic removing an inhibitory influence on sodium excretion.

Volume expansion during NOS substrate donation with l-arginine: regulatory offsetting of renal response?

2002 ◽  
Vol 282 (4) ◽  
pp. R1149-R1155 ◽  
Author(s):  
Jens Lundbæk Andersen ◽  
Niels C. F. Sandgaard ◽  
Peter Bie
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Sodium Excretion ◽  
Volume Expansion ◽  
Free Water ◽  
Urine Osmolality ◽  
Urine Flow ◽  
Ang Ii ◽  
Free Water Clearance ◽  
Arterial Blood

The responses to infusion of nitric oxide synthase substrate (l-arginine 3 mg · kg−1 · min−1) and to slow volume expansion (saline 35 ml/kg for 90 min) alone and in combination were investigated in separate experiments. l-Arginine left blood pressure and plasma ANG II unaffected but decreased heart rate (6 ± 2 beats/min) and urine osmolality, increased glomerular filtration rate (GFR) transiently, and caused sustained increases in sodium excretion (fourfold) and urine flow (0.2 ± 0.0 to 0.7 ± 0.1 ml/min). Volume expansion increased arterial blood pressure (102 ± 3 to 114 ± 3 mmHg), elevated GFR persistently by 24%, and enhanced sodium excretion to a peak of 251 ± 31 μmol/min, together with marked increases in urine flow, osmolar and free water clearances, whereas plasma ANG II decreased (8.1 ± 1.7 to 1.6 ± 0.3 pg/ml). Combined volume expansion and l-arginine infusion tended to increase arterial blood pressure and increased GFR by 31%, whereas peak sodium excretion was enhanced to 335 ± 23 μmol/min at plasma ANG II levels of 3.0 ± 1.1 pg/ml; urine flow and osmolar clearance were increased at constant free water clearance. In conclusion, l-arginine 1) increases sodium excretion, 2) decreases basal urine osmolality, 3) exaggerates the natriuretic response to volume expansion by an average of 50% without persistent changes in GFR, and 4) abolishes the increase in free water clearance normally occurring during volume expansion. Thus l-arginine is a natriuretic substance compatible with a role of nitric oxide in sodium homeostasis, possibly by offsetting/shifting the renal response to sodium excess.

Renal nerves and renal responses to volume expansion in conscious monkeys

1988 ◽  
Vol 255 (3) ◽  
pp. R388-R394 ◽  
Author(s):  
T. V. Peterson ◽  
B. A. Benjamin ◽  
N. L. Hurst
Keyword(s):  
Blood Volume ◽  
Sodium Excretion ◽  
Volume Expansion ◽  
Renal Denervation ◽  
Renal Excretion ◽  
Isotonic Saline ◽  
Urine Flow ◽  
Renal Nerves ◽  
Blood Volume Expansion ◽  
Renal Responses

Experiments were performed in conscious macaque monkeys to determine the effect of renal denervation on the diuresis and natriuresis of blood volume expansion. When the kidneys were innervated, expansion of estimated blood volume by 20% with 3% dextran in isotonic saline caused increases in urine flow (V), from 0.28 +/- 0.07 ml/min to a peak response of 1.08 +/- 0.20 ml/min, absolute sodium excretion (UNaV), from 30.0 +/- 11.2 to 99.8 +/- 11.7 mueq/min, and fractional sodium excretion (FENa+), from 1.24 +/- 0.51 to 3.19 +/- 0.56%. The animals then underwent bilateral renal denervation and were volume expanded a second time 6-13 days postdenervation. Under this condition, V increased from 0.32 +/- 0.05 to 0.64 +/- 0.08 ml/min, UNaV, from 22.2 +/- 4.6 to 46.2 +/- 8.0 mueq/min, and FENa+, from 0.91 +/- 0.26 to 1.92 +/- 0.41%, these increases being significantly less than when the kidneys were innervated. These results demonstrate that the renal nerves play an important role in the nonhuman primate in mediating increases in renal excretion during hypervolemia.

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