Sodium and lithium handling in the isolated hypertensive rat kidney

1989 ◽  
Vol 76 (3) ◽  
pp. 335-341 ◽  
Author(s):  
J. D. Firth ◽  
A. E. G. Raine ◽  
J. G. G. Ledingham
Keyword(s):  
Proximal Tubule ◽  
Sodium Excretion ◽  
Perfusion Pressure ◽  
Rat Kidney ◽  
Intrinsic Property ◽  
Sodium Reabsorption ◽  
Humoral Factors ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Sodium Handling

1. Isolated kidneys taken from spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY) were perfused over a range of perfusion pressures. 2. Lithium clearance was used as an index of proximal tubule sodium handling. 3. When the perfusate contained an oncotic agent (albumin, 6.7 g/dl) the SHR kidneys performed differently from the WKY kidneys with a reduction in inulin clearance, sodium excretion, fractional sodium excretion and fractional lithium excretion [at 105 mmHg (14 kPa) perfusion pressure, SHR 6.0 ± 1.1% vs WKY 12.6 ± 2.4% (mean ± sem); at 150 mmHg (20 kPa), SHR 17.1 ± 1.6% vs WKY 27.0 ± 2.3%]. Calculated indices of distal tubular function showed no major differences between SHR and WKY. 4. When kidneys were perfused without oncotic agent in the perfusate the differences between SHR and WKY in tubular handling of sodium and lithium were largely abolished. 5. These findings are consistent with the hypothesis that increased sodium reabsorption occurs in the proximal tubules of the kidneys of SHR and suggest that this is an intrinsic property of the kidney, not immediately dependent on neural or humoral factors. Increased sodium reabsorption in the proximal tubule may contribute significantly to the existence of hypertension in the SHR.

Alpha 2-adrenoceptors and sodium reabsorption in the isolated perfused rat kidney

1984 ◽  
Vol 247 (4) ◽  
pp. F680-F685 ◽  
Author(s):  
D. D. Smyth ◽  
S. Umemura ◽  
W. A. Pettinger
Keyword(s):  
Adenylate Cyclase ◽  
Sodium Excretion ◽  
Perfusion Pressure ◽  
Rat Kidney ◽  
Blocking Agent ◽  
Sodium Reabsorption ◽  
Sodium Retention ◽  
Sympathoadrenal System ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

Alpha 2-Adrenoceptors are known to inhibit adenylate cyclase in a number of tissues, but their function in the kidney is unknown. Adenylate cyclase and sodium excretion were stimulated with furosemide (30 microM) in the rat kidney perfused with Krebs-Henseleit solution (albumin 6.5 g/100 ml, 36 degrees C). beta-Adrenoceptors and alpha 1-adrenoceptors were blocked by propranolol (100 nM) and prazosin (30 nM) in the perfusate. Urinary cAMP and sodium excretion increased with furosemide. Activation of alpha 2-adrenoceptors with epinephrine (28 nM) caused no change in perfusion pressure or flow but decreased urinary cAMP and sodium excretion. These effects of epinephrine were reversed by the alpha 2-selective adrenoceptor blocking agent yohimbine (300 nM). Thus, in the setting of furosemide-stimulated sodium excretion and an associated elevation of adenylate cyclase, alpha 2-adrenoceptor stimulation resulted in sodium retention and inhibition of adenylate cyclase. By this receptor mechanism the sympathoadrenal system may contribute to retention of sodium.

Abnormal pressure-diuresis-natriuresis response in spontaneously hypertensive rats

1985 ◽  
Vol 248 (2) ◽  
pp. F199-F205 ◽  
Author(s):  
R. J. Roman ◽  
A. W. Cowley
Keyword(s):  
Sodium Excretion ◽  
Spontaneously Hypertensive Rats ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Urine Flow ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Fourfold Increase ◽  
Renal Perfusion Pressure ◽  
Wistar Kyoto

The renal responses to changes in perfusion pressure (RPP) were studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) to determine whether an abnormality in the pressure-diuresis phenomenon could be involved in the resetting of kidney function in hypertension. Differences in the neural and endocrine background to the kidneys were minimized by denervating the kidney and by holding plasma vasopressin, aldosterone, corticosterone, and norepinephrine levels constant by intravenous infusion. In WKY, increasing renal perfusion pressure 54 mmHg, from 103 to 157 mmHg, produced a ninefold increase in urine flow and sodium excretion with no measurable change in renal blood flow (RBF) or glomerular filtration rate (GFR). In SHR, increasing renal perfusion pressure 54 mmHg, from 133 to 187 mmHg, produced only a fourfold increase in urine flow and sodium excretion. GFR, RBF, and peritubular capillary pressures were well autoregulated and were similar in the SHR and WKY at pressures above 110 mmHg. These results indicate the presence of intrinsic changes in the kidney of SHR that enhance fractional tubular reabsorption and impair the pressure-diuresis response. This blunting of the renal pressure-diuresis phenomenon in SHR may represent the functional resetting of the kidney that is necessary for sustained hypertension.

Abnormal regulation of renal proximal tubule Na(+)-K(+)-ATPase by G proteins in spontaneously hypertensive rats

1994 ◽  
Vol 267 (6) ◽  
pp. F1069-F1075 ◽  
Author(s):  
R. W. Gurich ◽  
R. E. Beach
Keyword(s):  
Atpase Activity ◽  
Proximal Tubule ◽  
G Proteins ◽  
Spontaneously Hypertensive Rats ◽  
Renal Proximal Tubule ◽  
Sodium Reabsorption ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Regulatory Pathways ◽  
Wistar Kyoto

Enhanced salt reabsorption by the kidney, which may arise from impaired regulation of proximal tubule Na(+)-K(+)-ATPase activity, has a central role in the pathogenesis of essential hypertension. Guanine nucleotide binding proteins (G proteins) are involved in many regulatory pathways and have been implicated in the regulation of proximal tubule Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity. The present study was designed to evaluate further the regulation of Na(+)-K(+)-ATPase activity by G proteins in proximal tubule suspensions from Wistar-Kyoto rats (WKY) and to determine whether such regulation is abnormal in spontaneously hypertensive rats (SHR). Cholera toxin (CTX) inhibited Na(+)-K(+)-ATPase activity by approximately 40% in WKY but had no effect on Na(+)-K(+)-ATPase activity in SHR. In WKY, pretreatment of tubules with pertussis toxin (PTX), followed by the application of dopamine, inhibited Na(+)-K(+)-ATPase activity significantly, compared with the inhibition produced by dopamine alone. In SHR, dopamine alone did not inhibit Na(+)-K(+)-ATPase activity. However, in the presence of PTX, dopamine inhibited Na(+)-K(+)-ATPase activity significantly. These studies indicate that the renal proximal tubule Na(+)-K(+)-ATPase in WKY is regulated by both a PTX- and CTX-sensitive G protein(s) and that this regulation is abnormal in SHR. Such a defect could cause enhanced sodium reabsorption in SHR and contribute to the pathogenesis of hypertension in this model.

Interactions between ADH and prostaglandins in isolated erythrocyte-perfused rat kidney

1987 ◽  
Vol 252 (2) ◽  
pp. F331-F337 ◽  
Author(s):  
W. Lieberthal ◽  
M. L. Vasilevsky ◽  
C. R. Valeri ◽  
N. G. Levinsky
Keyword(s):  
Sodium Excretion ◽  
Rat Kidney ◽  
Urine Osmolality ◽  
Sodium Reabsorption ◽  
Urinary Osmolality ◽  
Hemodynamic Characteristics ◽  
Urinary Concentrating Ability ◽  
Tubular Morphology ◽  
Isolated Kidneys

Interactions between antidiuretic hormone (ADH) and renal prostaglandins in the regulation of sodium reabsorption and urinary concentrating ability were studied in isolated erythrocyte-perfused rat kidneys (IEPK). In this model, hemodynamic characteristics are comparable to those found in vivo, and tubular morphology is preserved throughout the period of perfusion. [Deamino]-D-arginine vasopressin (dDAVP) markedly reduced fractional sodium excretion (FE Na) in the IEPK from 3.5 +/- 0.6 to 0.45 +/- 0.14%. After indomethacin, FE Na fell still further to 0.08 +/- 0.02%. In the absence of dDAVP indomethacin had no effect on sodium excretion; FE Na was 2.4 +/- 0.6% in control and 2.0 +/- 0.4% in indomethacin-treated groups. dDAVP increased urine osmolality in the IEPK to 741 +/- 26 mosmol/kg. When prostaglandin synthesis was blocked with indomethacin, urinary osmolality increased further to 1,180 +/- 94 mosmol/kg. In isolated kidneys perfused without erythrocytes (IPK), dDAVP decreased FENa from 14.5 +/- 1.8% to 9.6 +/- 1.2%; addition of indomethacin had no further effect. dDAVP increased urine osmolality only modestly to 350 +/- 12 mosmol/kg in the IPK and indomethacin did not increase concentrating ability further (342 +/- 7 mosmol/kg). Thus the IEPK (unlike the IPK) can excrete a markedly hypertonic urine in response to ADH. ADH also enhances tubular reabsorption of sodium in the IEPK. Prostaglandins inhibit both these actions of ADH but do not directly affect sodium excretion in the absence of the hormone.

scholarly journals Loss of NHERF-1 expression prevents dopamine-mediated Na-K-ATPase regulation in renal proximal tubule cells from rat models of hypertension: aged F344 rats and spontaneously hypertensive rats

2017 ◽  
Vol 313 (2) ◽  
pp. C197-C206 ◽  
Author(s):  
Michelle T. Barati ◽  
Corey J. Ketchem ◽  
Michael L. Merchant ◽  
Walter B. Kusiak ◽  
Pedro A. Jose ◽  
...  
Keyword(s):  
Animal Models ◽  
Proximal Tubule ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Proximal Tubule Cells ◽  
Spontaneously Hypertensive ◽  
Sodium Hydrogen Exchanger ◽  
Tubule Cells ◽  
Wistar Kyoto ◽  
F344 Rats

Dopamine decreases Na-K-ATPase (NKA) activity by PKC-dependent phosphorylation and endocytosis of the NKA α1. Dopamine-mediated regulation of NKA is impaired in aging and some forms of hypertension. Using opossum (OK) proximal tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) associates with NKA α1 and dopamine-1 receptor (D1R). This association is required for the dopamine-mediated regulation of NKA. In OK cells, dopamine decreases NHERF-1 association with NKA α1 but increases its association with D1R. However, it is not known whether NHERF-1 plays a role in dopamine-mediated NKA regulation in animal models of hypertension. We hypothesized that defective dopamine-mediated regulation of NKA results from the decrease in NHERF-1 expression in rat renal PTCs isolated from animal models of hypertension [spontaneously hypertensive rats (SHRs) and aged F344 rats]. To test this hypothesis, we isolated and cultured renal PTCs from 22-mo-old F344 rats and their controls, normotensive 4-mo-old F344 rats, and SHRs and their controls, normotensive Wistar-Kyoto (WKY) rats. The results demonstrate that in both hypertensive models (SHR and aged F344), NHERF-1 expression, dopamine-mediated phosphorylation of NKA, and ouabain-inhibitable K+ transport are reduced. Transfection of NHERF-1 into PTCs from aged F344 and SHRs restored dopamine-mediated inhibition of NKA. These results suggest that decreased renal NHERF-1 expression contributes to the impaired dopamine-mediated inhibition of NKA in PTCs from animal models of hypertension.

Acute renal denervation produces a diuresis and natriuresis in young SHR but not WKY rats

1986 ◽  
Vol 251 (4) ◽  
pp. F655-F661 ◽  
Author(s):  
M. A. Rudd ◽  
R. S. Grippo ◽  
W. J. Arendshorst
Keyword(s):  
Sodium Excretion ◽  
Renal Denervation ◽  
Strain Differences ◽  
Urine Flow ◽  
Sprague Dawley ◽  
Renal Vasculature ◽  
Renal Nerve ◽  
Water Excretion ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Clearance experiments were conducted to determine the effect of acute unilateral renal denervation (DNX) on renal hemodynamics and salt and water excretion in anesthetized 6-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto genetic control rats (WKY). Before DNX, SHR had higher mean arterial pressure (33%) and renal vascular resistance (RVR) (57%) and lower glomerular filtration rate (GFR) (10%); urine flow and sodium excretion were similar. Following DNX in SHR, sodium and water excretion increased by 138 and 62%, respectively (P less than 0.001); GFR and RVR were unchanged. In contrast, DNX in WKY did not affect urine flow (0%) or sodium excretion (-21%). These strain differences were observed in Okamoto-Aoki rats from two sources. Effective DNX was indicated by 95% reduction of norepinephrine content 3 days after DNX in both strains. Six-week-old Sprague-Dawley and Munich-Wistar rats, in contrast to WKY, responded to DNX with a natriuresis (+182%) and diuresis (+95%) (P less than 0.001). Renal function was unaffected by sham DNX in SHR. Our results indicate that efferent renal nerve activity has little tonic influence on the renal vasculature in these young rats. Augmented neurotransmitter release and/or tubular responsiveness may be involved in fluid and electrolyte retention and the pathogenesis of hypertension in SHR. Conversely, blunted renal neuroeffector responses may prevent WKY from developing hypertension.

A rapid bioassay for quantification of atrial natriuretic polypeptides

1987 ◽  
Vol 252 (5) ◽  
pp. R1009-R1014 ◽  
Author(s):  
K. Matsui ◽  
T. Kimura ◽  
K. Ota ◽  
M. Shoji ◽  
M. Inoue ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Urine Volume ◽  
Good Tool ◽  
Spontaneously Hypertensive ◽  
Assay Procedure ◽  
Rapid Bioassay ◽  
Wistar Kyoto ◽  
Dose Dependent ◽  
Atrial Natriuretic

A quantitative bioassay for the detection and quantification of atrial natriuretic polypeptides (ANPs) was developed in a pentobarbital-anesthetized rat. Ten percent mannitol in 0.9% saline was infused to achieve stable diuresis. The conductivity of the urine, urine flow, and blood pressure were continuously recorded. A bolus injection of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) elicited dose-dependent increases in the urine conductivity, sodium excretion, and urine volume. Changes in the urine conductivity correlated significantly with the increase in sodium excretion. By use of changes in urine conductivity, biological ANP activity of crude rat atrial extract was determined. Atrial contents of ANP in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were 25.5 +/- 1.2 microgram per atrium (n = 4) and 25.1 +/- 0.8 (n = 5) in euhydration. They were increased to 27.0 +/- 1.1 micrograms (n = 4) and 29.3 +/- 1.3 (n = 5, P less than 0.05), after 5-day water deprivation, respectively. This assay procedure provides a good tool for rapid and quantitative determination of ANPs.

Effect of renal perfusion pressure on sodium reabsorption from proximal tubules of superficial and deep nephrons

1986 ◽  
Vol 250 (3) ◽  
pp. F425-F429 ◽  
Author(s):  
J. A. Haas ◽  
J. P. Granger ◽  
F. G. Knox
Keyword(s):  
Proximal Tubule ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Proximal Tubules ◽  
Sodium Reabsorption ◽  
Renal Perfusion Pressure ◽  
Henle's Loop ◽  
Acute Change ◽  
Acute Changes ◽  
Superficial And Deep Nephrons

Previous studies in rats have demonstrated that superficial proximal tubule sodium reabsorption does not change in response to alterations in renal perfusion pressure (RPP). The first objective of the present study was to estimate sodium reabsorption in response to acute changes in RPP utilizing fractional lithium reabsorption (FRLi) as an index of fractional sodium reabsorption (FRNa) by the proximal tubule of the kidney as a whole. FRLi decreased in response to increases in RPP, suggesting that sodium reabsorption by the proximal tubule of some nephron population is decreased. Therefore, the second objective of the present study was to test the hypothesis that superficial and deep proximal tubules respond differently to changes in RPP by comparing proximal tubule sodium reabsorption from both nephron populations. In response to an acute change in RPP from 114 +/- 4 to 138 +/- 5 mmHg, FRNa by the proximal tubule and descending limb of Henle's loop in deep nephrons decreased from 71.3 +/- 2.3 to 55.8 +/- 5.6%, but FRNa by the superficial late proximal tubule was not changed: (44.3 +/- 4.8 to 45.1 +/- 3.9%). The urinary fractional reabsorption of sodium decreased from 96.7 +/- 0.6 to 94.5 +/- 0.5%. In summary, these studies demonstrate that increases in RPP have no effect on sodium reabsorption by the proximal tubule of superficial nephrons. In contrast, sodium delivery to the point of micropuncture in the descending limb of Henle's loop of deep nephrons was increased, suggesting inhibition of sodium reabsorption by proximal tubules of deep nephrons in response to increases in RPP.

Mechanism of exaggerated diuresis in spontaneously hypertensive rats

1978 ◽  
Vol 235 (5) ◽  
pp. F409-F416 ◽  
Author(s):  
Gerald F. DiBona ◽  
Linda L. Rios
Keyword(s):  
Volume Expansion ◽  
Spontaneously Hypertensive Rats ◽  
Spontaneously Hypertensive Rat ◽  
Renal Perfusion ◽  
Sodium Reabsorption ◽  
Loop Of Henle ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Single Nephron ◽  
Wistar Kyoto

The mechanism of exaggerated diuresis and natriuresis was studied in spontaneously hypertensive rats (SHR) by renal clearance and micropuncture techniques. Control normotensive rats of the same age and sex [Wistar-Kyoto rats (WKY)] were also studied. During the hydropenic control and the volume-expansion experimental periods absolute and fractional water and sodium excretion were greater in SHR than in WKY. Although fractional and absolute water and sodium reabsorption were similar along the proximal convolution in SHR and WKY, fractional and absolute water reabsorption in Henle's loop was less in SHR than in WKY. Hydrostatic and colloid osmotic pressures in the cortical peritubular microvasculature were similar in WKY and SHR. Acute normalization of renal perfusion pressure by aortic constriction reversed the exaggerated diuresis and natriuresis in SHR by halving the filtered load of water and sodium; whole kidney and single nephron glomerular filtration rates and blood flows decreased by 50%. It is concluded that the exaggerated diuresis and natriuresis of the spontaneously hypertensive rat is caused by a decreased reabsorption in the loop of Henle. The mechanism of this decreased reabsorption in the loop of Henle cannot be explained by alterations in the measured physical forces in the renal cortical microvasculature. natriuresis; autoregulation; volume expansion Submitted on November 15, 1977 Accepted on June 7, 1978

Stimulation of renin release in perfused kidney by low calcium and high magnesium

1977 ◽  
Vol 232 (4) ◽  
pp. F377-F382 ◽  
Author(s):  
J. S. Fray
Keyword(s):  
Sodium Excretion ◽  
Calcium Concentration ◽  
Perfusion Pressure ◽  
Rat Kidney ◽  
Sodium Concentration ◽  
Renin Release ◽  
Isolated Perfused Rat Kidney ◽  
Low Calcium ◽  
Perfused Rat Kidney ◽  
Stimulation Of

These experiments were designed to test whether changing perfusate calcium or magnesium concentrations affected renin release in the isolated perfused rat kidney, and whether kidneys removed from sodium-loaded or sodium-deprived rats released the same amount of renin in response to identical stimuli. Kidneys were perfused with Kreb-Henseleit solution containing albumin. Renin release was inversely related to perfusate calcium concentration, whereas renin release was directly related to perfusate magnesium. Although a low calcium medium or low perfusion pressure (50 mmHg) stimulated renin release, the release was substantially greater in the sodium-deprived rats. Increasing the perfusate sodium concentration from 85 to 206 mM increased excretion, but did not alter renin release. It is concluded that a) low perfusate calcium and high magnesium concentrations stimulate renin release, b) kidneys removed from sodium-deprived rats released substantially more renin thatn those from sodium-loaded rats, and c) changing perfusate sodium concentration alters sodium excretion, but does not affect renin release.

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