Defect in the Renal Tubular Reabsorption of Water Associated With Potassium Depletion in Rats

The effect of graded degrees of K depletion on the ability to produce a concentrated urine was studied in Sprague-Dawley rats. With increasing degrees of K depletion, as measured by the concentration of K in fat-free skeletal muscle, there was a progrossive decrease in the maximum urinary concentration. This defect of the renal concentrating mechanism appeared to be better correlated with the degree than with the duration of potassium depletion and could be demonstrated either by the use of exogenous vasopressin or by water deprivation. The potassium-deficient rats in at least one experiment developed a significant polydipsia. The data do not allow any conclusions with respect to the relationship of the polydipsia to the renal concentrating defect except that the latter at least was not severe at the onset of the increased water intake.

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Effect of potassium depletion on cerebrospinal fluid bicarbonate homeostasis

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1976.231.2.579 ◽

1976 ◽

Vol 231 (2) ◽

pp. 579-587 ◽

Cited By ~ 11

Author(s):

EE Nattie ◽

SM Tenney

Keyword(s):

Potassium Depletion ◽

Acid Base Balance ◽

Acid Base ◽

Arterial Pco2 ◽

Mixed Acid ◽

Base Balance ◽

Upward Direction ◽

Relationship Of ◽

The Relationship ◽

K Depletion

We have examined the effect of K depletion on CSF [HCO3-] homeostasis in awake rats. The relationship of CSF [HCO3-] to arterial [HCO3-] in metabolic acid-base disturbances is displaced is an upward direction and has a significantly increased slope in K-depleted vs. control rats (0.51 +/- 0.02 vs. 0.42 +/- 0.02). Results of partial K-repletion experiments, with peripheral acid-base balance held constant, suggest that the effect is K specific. The K-depleted animals also exhibit a wider (CSF-arterial) PCO2 difference than controls (11.1 vs. 8.4 mmHg). When CSF [HCO3-] is shown as a function of CSF PCO2 the data of K-depleted rats are no longer displaced when compared to controls but still have a significantly greater slope (1.21 +/- 0.23 vs. 0.89 +/- 0.08). This increased slope is interpreted to reflect enhanced HCO3- movement from blood to CSF at high arterial [HCO3-]. Analysis of our data and observations from the literature in conditions of mixed acid-base disturbances suggest that CSF [HCO3-] is determined by a) CSF PCO2 and b) the level of arterial [HCO3-] when the latter is greater than the normal CSF [HCO3-].

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Emotional Behavior and Adrenal Function in the Rat

Psychological Reports ◽

10.2466/pr0.1965.16.1.283 ◽

1965 ◽

Vol 16 (1) ◽

pp. 283-286 ◽

Cited By ~ 20

Author(s):

William P. Pare ◽

Joseph W. Cullen

Keyword(s):

Open Field ◽

Avoidance Conditioning ◽

Emotional Behavior ◽

Adrenal Weight ◽

Sprague Dawley ◽

Daily Trial ◽

Meaningful Relationship ◽

Sprague Dawley Rats ◽

Relationship Of ◽

The Relationship

The relationship of open-field behaviors (latency, ambulation, rearing, and defecation) and adrenal weight and adrenal ascorbic acid (AAA) was investigated. 38 male Sprague-Dawley rats received one daily trial in the open field for 4 days. Measures of adrenal weight and AAA were subsequently obtained. Correlations between variables indicated no meaningful relationship between emotional defecation and adrenal responses. Rearing correlated significantly with AAA. Latency was significantly related with adrenal weight. These results are consistent with recent studies investigating performance of emotional Ss on escape-avoidance conditioning and CER behavior.

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Mechanism underlying diuretic effect of l-NAME at a subpressor dose

AJP Renal Physiology ◽

10.1152/ajprenal.2001.281.3.f414 ◽

2001 ◽

Vol 281 (3) ◽

pp. F414-F419 ◽

Cited By ~ 14

Author(s):

Mingyu Liang ◽

Theresa J. Berndt ◽

Franklyn G. Knox

Keyword(s):

Proximal Tubule ◽

Flow Rate ◽

Nitrate Concentration ◽

Distal Tubule ◽

No Synthase ◽

Urine Flow ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Renal Tubular ◽

Nitrite Nitrate

The diuretic effects of nitric oxide (NO) synthase inhibitors administered at subpressor dose in rats are controversial, and the tubular segments involved are not known. In the present study, we examined the effect of N ω-nitro-l-arginine methyl ester (l-NAME) at a subpressor dose on renal interstitial NO and cGMP activity and on renal tubular segmental reabsorption of fluid in the rat. Intravenous infusion of l-NAME at 1 μg · kg−1 · min−1 in Sprague-Dawley rats ( N = 8), which did not alter mean arterial pressure or glomerular filtration rate, significantly increased urine flow rate (Uv; from 78.2 ± 12.7 to 117.1 ± 14.9 μl/min, P < 0.05). Paradoxically, this effect of l-NAME was concomitant with significant increases in nitrite/nitrate (from 10.79 ± 1.20 to 16.50 ± 2.60 μM, P < 0.05) and cGMP (from 0.65 ± 0.09 to 0.98 ± 0.18 nM, P < 0.05) concentrations in renal cortical microdialysate as well as the nitrite/nitrate concentration in the medullary microdialysate. Micropuncture studies in the superficial nephron revealed that l-NAME significantly increased the flow rate (from 8.3 ± 0.9 to 12.2 ± 1.2 nl/min, P < 0.05) and fractional delivery of fluid to the distal tubule, but not those in the late proximal tubule. In conclusion, l-NAME, at the subpressor dose used in this study, increased renal nitrate/nitrite and cGMP and inhibited fluid reabsorption in tubular segments between the late proximal tubule and the distal tubule of superficial nephrons.

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Role of arginine vasopressin in medullary thick ascending limb on maximal urinary concentration

AJP Renal Physiology ◽

10.1152/ajprenal.1986.251.2.f266 ◽

1986 ◽

Vol 251 (2) ◽

pp. F266-F270 ◽

Cited By ~ 5

Author(s):

J. K. Kim ◽

S. N. Summer ◽

A. E. Erickson ◽

R. W. Schrier

Keyword(s):

Adenylate Cyclase ◽

Arginine Vasopressin ◽

Urinary Concentration ◽

Thick Ascending Limb ◽

Sprague Dawley ◽

Urinary Osmolality ◽

Medullary Thick Ascending Limb ◽

Sprague Dawley Rats ◽

Collecting Tubules

Two groups of Sprague-Dawley rats, Harlan (H) and Charles River (CR), were discovered in that the medullary thick ascending limb (MAL) had a profoundly different adenylate cyclase response to arginine vasopressin (AVP). Using these two groups of rats, we studied the correlation between AVP action on the MAL and maximal urinary concentration. AVP (10(-6) M) significantly stimulated adenylate cyclase in MAL of H rats (7.4 +/- 0.9 to 43.8 +/- 4.6 fmol cAMP formed X 30 min-1 X mm-1, P less than 0.001) but not in CR rats (10.3 +/- 1.4 to 12.7 +/- 2.0 fmol cAMP formed X 30 min-1 X mm-1, NS). In contrast, AVP significantly stimulated adenylate cyclase of cortical, outer and inner medullary collecting tubules from both H and CR rats. Glucagon (10(-6) M) significantly stimulated adenylate cyclase of MAL from both H and CR rats. After 48 h of fluid deprivation, urinary osmolality was significantly higher (P less than 0.001) in the H (4,504 +/- 399 mosmol/kg H2O, n = 14) than CR (2,840 +/- 176 mosmol/kg H2O, n = rats. This observation was not attributable to differences in creatinine clearance (CR, 1.30 +/- 0.24; H, 1.24 +/- 0.03 ml/min, NS, n = 4) or plasma AVP (CR, 12.75 +/- 1.44; H, 12.38 +/- 1.17 pg/ml, NS, n = 6) levels. These results therefore suggest that the action of AVP on the MAL, in addition to the effect on collecting tubules, is involved in maximal urinary concentration in rats.

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Epidermal growth factor accelerates renal tissue repair in a model of gentamicin nephrotoxicity in rats

AJP Renal Physiology ◽

10.1152/ajprenal.1992.263.5.f806 ◽

1992 ◽

Vol 263 (5) ◽

pp. F806-F811 ◽

Cited By ~ 4

Author(s):

N. J. Morin ◽

G. Laurent ◽

D. Nonclercq ◽

G. Toubeau ◽

J. A. Heuson-Stiennon ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Binding Sites ◽

Renal Tissue ◽

Sprague Dawley ◽

Renal Tubular Cells ◽

Sprague Dawley Rats ◽

Epidermal Growth ◽

Renal Tubular ◽

Cessation Of Treatment

Epidermal growth factor (EGF) is a potent mitogen for renal tubular cells that possess specific high-affinity binding sites for this polypeptide. However, actual function of EGF within the kidney remains to be elucidated. We evaluated the effect of exogenous EGF administration on the rate of tubular regeneration in an experimental model of gentamicin (GT) nephrotoxicity. Female Sprague-Dawley rats were anesthetized, and a miniosmotic pump filled with mouse EGF or saline was implanted subcutaneously. Twenty-four hours later, GT (40 mg.kg-1 x 12 h-1 ip) was given for 4 and 8 days. Groups of treated animals and controls were killed either the day after cessation of treatment (days 5 and 9) or 4 and 8 days after the end of 8-day GT administration (days 12 and 16). Cortical GT levels of groups killed at days 5, 9, 12, and 16 were similar in animals infused with saline or EGF. Serum creatinine levels were significantly higher in GT-treated animals infused with EGF or saline and killed at days 9 and 12 compared with saline-treated animals infused with EGF or saline alone (P < 0.01). Blood urea nitrogen (BUN) also increased as a result of GT administration. However, in animals receiving GT and EGF and killed at day 16, mean BUN level was significantly lower (P < 0.01) compared with rats dosed with GT alone. In treated rats, the extent of tubular regeneration, evaluated by the rate of [3H]thymidine incorporation into renal cortical DNA or by the frequency of S-phase cells (histoautoradiography), was increased in a dose- and time-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

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Time course of airway hyperresponsiveness and remodeling induced by hyperoxia in rats

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1995.269.2.l227 ◽

1995 ◽

Vol 269 (2) ◽

pp. L227-L233 ◽

Cited By ~ 4

Author(s):

J. L. Szarek ◽

H. L. Ramsay ◽

A. Andringa ◽

M. L. Miller

Keyword(s):

Smooth Muscle ◽

Airway Hyperresponsiveness ◽

Time Course ◽

Electrical Field Stimulation ◽

Maximal Response ◽

Sprague Dawley ◽

Electrical Field ◽

Muscle Area ◽

Sprague Dawley Rats ◽

The Relationship

The purpose of this study was to answer two questions concerning hyperoxia-induced airway hyperresponsiveness: 1) What is the time course of the development of airway hyperresponsiveness? 2) What is the relationship between the increase in responsiveness and smooth muscle area? Segments of intrapulmonary bronchi were isolated from male Sprague-Dawley rats that had been exposed to 80-85% O2 for a period of 1, 3, 5, or 7 days and from aged-matched control animals that breathed room air. Hyperoxia increased the sensitivity (log concentration or frequency that elicited a half-maximal response) and reactivity (maximum tension developed) of the airways to electrical field stimulation (EFS) after 3, 5, and 7 days; sensitivity to acetylcholine was not affected, but reactivity was increased after 7 days. Hyperoxia increased smooth muscle area beginning 5 days after commencing the exposure. After normalizing tension responses to smooth muscle area, reactivity of the airways to the stimuli was not different between the two groups, but sensitivity to EFS was still increased. The increase in reactivity observed after 5 and 7 days of exposure can be explained by an increase in smooth muscle area that occurred at these time points. The fact that the sensitivity of the airways to EFS remained increased after normalization, together with the fact that the increase in airway responsiveness after 3 days of exposure occurred at a time when smooth muscle area was not different from control, suggests that mechanisms other than increased smooth muscle area contribute to the development of hyperoxia-induced airway hyperresponsiveness.

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A 90-day Sub-chronic Oral Toxicity Assessment of Mulberry Extract in Sprague Dawley Rats

INQUIRY The Journal of Health Care Organization Provision and Financing ◽

10.1177/00469580211056044 ◽

2021 ◽

Vol 58 ◽

pp. 004695802110560

Author(s):

Min Hong ◽

Min Lu ◽

Yimin Qian ◽

Liping Wei ◽

Yaqun Zhang ◽

...

Keyword(s):

Clinical Chemistry ◽

Recovery Period ◽

Safety Evaluation ◽

Toxicity Assessment ◽

Sprague Dawley ◽

Oral Toxicity ◽

Renal Tubular Cells ◽

Sprague Dawley Rats ◽

Adverse Effect Level ◽

Renal Tubular

Mulberry extract from Fructus Mori contains an anthocyanin pigment and has been widely used as a food additive in China and other Eastern Asian countries. Only few research has been done on toxicological profiling of mulberry extract for its safety evaluation; however, the data is inconclusive. In the current study, mulberry extract of 4200, 1400, or 466 mg/kg were orally administrated to Sprague Dawley rats for 90 consecutive days followed by a recovery period of 28 days. No abnormalities were detected in body weights, food intake, ophthalmological, hematological, coagulation, clinical chemistry, and organ weights parameters. Discoloration of urine (red, purple, and brown) and feces (black), along with bedding material (purple) were observed in the 4200 mg/kg group. Further, microscopic examination revealed brown granules in the renal tubular cells for rats in 4200 and 1400 mg/kg groups. Since these changes were associated with excretory effect of the extract, the No Observed Adverse Effect Level was determined to be 4200 mg/kg, which was equivalent to the 1058.5 mg/kg of anthocyanin.

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The Pharmacodynamic-Toxicodynamic Relationship of AUC and CMAX in Vancomycin Induced Kidney Injury in an Animal Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01945-20 ◽

2020 ◽

pp. AAC.01945-20

Author(s):

Sean N. Avedissian ◽

Gwendolyn Pais ◽

Jiajun Liu ◽

J. Nicholas O’Donnell ◽

Thomas P. Lodise ◽

...

Keyword(s):

Kidney Injury ◽

Information Criterion ◽

Compartment Model ◽

Model Fit ◽

Sprague Dawley ◽

P Values ◽

Exposure Response ◽

Sprague Dawley Rats ◽

Kidney Injury Molecule 1 ◽

Relationship Of

Vancomycin induces exposure-related acute kidney injury. However, the pharmacokinetic-toxicodynamic (PK-TD) relationship remains unclear. Sprague-Dawley rats received IV vancomycin doses of 300mg/kg/day and 400mg/kg/day, divided once, twice, thrice or 4xdaily (i.e., QD, BID, TID or QID) over 24-hours. Up to 8-samples were drawn during the 24-hour dosing period. Twenty-four-hour urine was collected and assayed for kidney injury molecule-1 (KIM-1). Vancomycin was quantified via LC-MS/MS. Following terminal sampling, nephrectomy and histopathologic analyses were conducted. PK analyses were conducted using Pmetrics. PK exposures (i.e. AUC0-24h, CMAX0-24h,) were calculated for each rat, and PK-TD relationships were discerned. A total of 53-rats generated PK-TD data. A 2-compartment model fit the data well (Bayesian observed vs. predicted concentrations, R2=0.96). KIM-1 values were greater in QD and BID groups (P-values: QD vs TID:<0.002, QD vs QID:<0.004, BID vs TID:<0.002, and BID vs QID:<0.004). Exposure–response relationships were observed between KIM-1 vs CMAX0-24h and AUC0–24h (R2 =  0.7 and 0.68). Corrected Akaike’s information criterion showed CMAX0-24h as most predictive PK-TD driver for vancomycin-induced kidney injury (VIKI) (-5.28 versus -1.95).While PK-TD indices are often inter-correlated, maximal concentrations and fewer doses (for the same total daily amount) resulted in increased VIKI in our rat model.

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Pressor resistance to vasopressin in sodium depletion, potassium depletion, and cirrhosis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.251.3.r525 ◽

1986 ◽

Vol 251 (3) ◽

pp. R525-R530 ◽

Cited By ~ 3

Author(s):

B. M. Murray ◽

M. S. Paller

Keyword(s):

Pressor Response ◽

Potassium Depletion ◽

Pressor Effect ◽

Sodium Depletion ◽

Sprague Dawley ◽

Low Sodium Diet ◽

Low Sodium ◽

Sprague Dawley Rats ◽

Low Potassium ◽

Baroreceptor Reflexes

Resistance to the pressor effects of angiotensin II, but not norepinephrine, has been observed in sodium depletion, potassium depletion, and cirrhosis. We tested the response to arginine vasopressin (AVP) in each of these conditions. Male Sprague-Dawley rats were made sodium depleted with furosemide and a low-sodium diet for 3 days, potassium depleted by feeding a low-potassium diet for 14-21 days, or cirrhotic by inhalation of carbon tetrachloride for 8 wk. In conscious rats, the pressor response to graded doses of AVP was reduced in sodium depletion by 27-43% compared with control rats. Sodium-depleted rats were also found to have enhanced baroreceptor reflexes, since the decrease in heart rate for a given increase in mean arterial pressure was greater than in control rats. When the ganglionic blocker pentolinium tartrate was given to sodium-depleted rats the pressor response to AVP was restored to control levels. In potassium-depleted rats the pressor response to AVP was 21-52% lower than that in controls, whereas cirrhotic rats also had a blunted response to AVP (14-41% lower than control). However, there was no evidence in either of these two states of enhanced baroreceptor activity, and pretreatment with pentolinium tartrate did not restore the pressor response to normal. Therefore, although resistance to the pressor effect of AVP was found in all three conditions, the mechanism of this effect was different in sodium depletion compared with potassium depletion and cirrhosis. We conclude that resistance to the pressor action of AVP in sodium depletion was secondary to resetting of the baroreceptors.

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