Vasopressin resistance in potassium depletion: role of Na-K pump

1992 ◽  
Vol 263 (4) ◽  
pp. F705-F710 ◽  
Author(s):  
S. K. Mujais ◽  
Y. Chen ◽  
N. A. Nora
Keyword(s):  
Collecting Duct ◽  
Cortical Collecting Duct ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Pump Activity ◽  
Before And After ◽  
Directional Change ◽  
Medullary Collecting Duct ◽  
Low K ◽  
K Depletion

Resistance to the hydrosmotic effects of vasopressin has been described in K depletion. It is not clear whether other effects of vasopressin, notably its effects on the Na-K pump in the collecting duct, are similarly affected. Adrenalectomized male Sprague-Dawley rats were allocated to either a normal K (NK) or low-K (LK) diet. Na-K pump activity (pmol.mm-1.h-1) in cortical collecting duct (CCD) and medullary collecting duct (MCD) was determined at 21 days after allocation to the dietary groups before and after exogenous vasopressin (0.1 U twice daily for 3 days). In animals on NK diet, vasopressin (AVP) led to a doubling of Na-K pump activity in the CCD from 502 +/- 47 to 1,144 +/- 41 pmol.mm-1.h-1 (P < 0.01). In K-depleted animals, which had a higher baseline Na-K pump activity, an increase was also observed from 1,056 +/- 97 to 1,239 +/- 65 pmol.mm-1.h-1 (P < 0.05), but this increase was quantitatively less, with the change being 183 vs. 642 pmol.mm-1.h-1 in K-replete rats. The findings in the MCD were similar; in rats on a NK diet, AVP led to a significant increase in Na-K pump activity from 498 +/- 29 to 830 +/- 28 pmol.mm-1.h-1 (P < 0.01). With K depletion, this directional change was preserved, increasing from 1,380 +/- 49 to 1,556 +/- 45 pmol.mm-1.h-1 (P < 0.05), but was quantitatively less than in K-replete rats, the change being 176 vs. 332 pmol.mm-1.h-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Discordant aspects of aldosterone resistance in potassium depletion

1992 ◽  
Vol 262 (6) ◽  
pp. F972-F979 ◽  
Author(s):  
S. K. Mujais ◽  
Y. Chen ◽  
N. A. Nora
Keyword(s):  
Biochemical Response ◽  
Sprague Dawley ◽  
Short Term ◽  
Sprague Dawley Rats ◽  
Pump Activity ◽  
Before And After ◽  
Collecting Tubules ◽  
Low K ◽  
K Depletion

Aldosterone resistance, defined as absent kaliuretic response to exogenous hormone, has been described in K depletion. It is not clear whether the absent kaliuresis is due to activation of K-conserving mechanisms or to failure of activation of the Na-K pump in cortical collecting tubules (CCT) by mineralocorticoids. Adrenalectomized male Sprague-Dawley rats were allocated to either a normal or low-K diet. Na-K pump activity (pmol.mm-1.h-1) in microdissected CCT and medullary collecting tubules (MCT, inner stripe of the outer medulla) was determined at 7 or 21 days after allocation to the dietary groups before and after exogenous aldosterone (50 micrograms twice daily, for 3 days). K depletion led to progressive hypertrophic changes in the CCT and MCT manifest in an increase in basal Na-K pump activity. In both K repletion and short-term K depletion (7 days), aldosterone led to the expected increase in CCT Na-K pump activity. With long-term K depletion, the CCT Na-K pump response to aldosterone was blunted. In the MCT where under normal conditions the Na-K pump is aldosterone unresponsive, an increasing aberrant responsiveness to the mineralocorticoid was observed with progressive K depletion. We conclude that apparent aldosterone resistance in short-term K depletion is likely due to activation of K-conserving mechanisms with early preservation of the CCT biochemical response to the hormone. With long-term K depletion, a blunted biochemical response to aldosterone may contribute to the absent kaliuretic response. In the MCT, K depletion led to the development of aberrant responsiveness to aldosterone.

scholarly journals Chronic lithium treatment induces novel patterns of pendrin localization and expression

2018 ◽  
Vol 315 (2) ◽  
pp. F313-F322
Author(s):  
Nathaniel J. Himmel ◽  
Yirong Wang ◽  
Daniel A. Rodriguez ◽  
Michael A. Sun ◽  
Mitsi A. Blount
Keyword(s):  
Collecting Duct ◽  
Lithium Treatment ◽  
Urine Osmolality ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Sprague Dawley ◽  
Cell Plasticity ◽  
Acid Base ◽  
Sprague Dawley Rats ◽  
Medullary Collecting Duct

Prolonged lithium treatment is associated with various renal side effects and is known to induce inner medullary collecting duct (IMCD) remodeling. In animals treated with lithium, the fraction of intercalated cells (ICs), which are responsible for acid-base homeostasis, increases compared with renal principal cells (PCs). To investigate the intricacies of lithium-induced IMCD remodeling, male Sprague-Dawley rats were fed a lithium-enriched diet for 0,1, 2, 3, 6, 9, or 12 wk. Urine osmolality was decreased at 1 wk, and from 2 to 12 wk, animals were severely polyuric. After 6 wk of lithium treatment, approximately one-quarter of the cells in the initial IMCD expressed vacuolar H+-ATPase, an IC marker. These cells were localized in portions of the inner medulla, where ICs are not normally found. Pendrin, a Cl−/[Formula: see text] exchanger, is normally expressed only in two IC subtypes found in the convoluted tubule, the cortical collecting duct, and the connecting tubule. At 6 wk of lithium treatment, we observed various patterns of pendrin localization and expression in the rat IMCD, including a novel phenotype wherein pendrin was coexpressed with aquaporin-4. These observations collectively suggest that renal IMCD cell plasticity may play an important role in lithium-induced IMCD remodeling.

Cortical collecting duct Na-K pump in obstructive nephropathy

1990 ◽  
Vol 258 (5) ◽  
pp. F1320-F1327 ◽  
Author(s):  
H. Kimura ◽  
S. K. Mujais
Keyword(s):  
Ureteral Obstruction ◽  
Turnover Rate ◽  
Collecting Duct ◽  
Obstructive Nephropathy ◽  
Cortical Collecting Duct ◽  
Sprague Dawley ◽  
Irreversible Damage ◽  
Sprague Dawley Rats ◽  
Collecting Tubule

The present study examined the alterations in the cortical collecting tubule (CCT) Na-K pump that occur after unilateral ureteral obstruction and their consequences on electrolyte excretion. In male Sprague-Dawley rats, unilateral ureteral ligation led to a progressive decrease in intact CCT Na-K pump in situ turnover worsening with the duration of the obstruction: control, 20.1 +/- 0.4; obstructed kidney: 3 h, 14.6 +/- 0.3; 12 h, 12.7 +/- 0.6; 24 h, 12.8 +/- 0.5; 48 h, 11.6 +/- 0.5; and 96 h, 10.6 +/- 0.4 pmol Rb.mm-1.min-1 (all P less than 0.001 vs. control). CCT diameter increased with the duration of obstruction. Release of ureteral obstruction was associated with restitution of pump turnover rate. With 3 h of obstruction, recovery of pump in situ turnover was complete (19.7 +/- 0.4 pmol Rb.mm-1.min-1) by 24 h after release. With more prolonged obstruction (24 h) recovery was partial by 24 h postrelease (16.2 +/- 0.5 pmol Rb.mm-1.min-1) and complete (19.8 +/- 0.7 pmol Rb.mm-1.min-1) by 48 h, suggesting a delay in recovery without the occurrence of irreversible damage. The impairment in Na-K pump in situ turnover was paralleled by an impairment in the ability of the obstructed kidney to excrete an acute potassium load. This parallelism of functional and biochemical studies favors the notion that impairment of CCT Na-K pump in situ turnover contributes significantly to the abnormal potassium excretion that accompanies obstructive damage.

Distribution of kallikrein-binding protein mRNA in kidneys and difference between SHR and WKY rats

1994 ◽  
Vol 267 (2) ◽  
pp. F325-F330 ◽  
Author(s):  
T. Yang ◽  
Y. Terada ◽  
H. Nonoguchi ◽  
M. Tsujino ◽  
K. Tomita ◽  
...  
Keyword(s):  
Blot Analysis ◽  
Binding Protein ◽  
Collecting Duct ◽  
Cortical Collecting Duct ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Sd Rats ◽  
Medullary Collecting Duct ◽  
Wistar Kyoto

We investigated kallikrein-binding protein (KBP) mRNA distribution in the kidney of Sprague-Dawley (SD) rats, spontaneously hypertensive rats (SHR), and Wistar-Kyoto strain (WKY) rats. Northern blot analysis revealed that KBP mRNA was located mainly in the medulla and with lower amounts in SHR than in WKY rats. KBP mRNA in microdissected nephron segments was detected by reverse transcription and polymerase chain reaction (RT-PCR) followed by Southern blot analysis. In SD rats, the most abundant signals were consistently found in inner medullary collecting duct (IMCD), with small amounts in outer medullary collecting duct, proximal convoluted tubule, and glomerulus. No signals were found in connecting tubule and cortical collecting duct. The nephron distribution of KBP mRNA was similar in WKY and SD rats. Only a small amount of signal was found, however, in IMCD of SHR. In conclusion, 1) KBP mRNA was predominantly distributed in the medullary segments of the distal nephron, downstream from the known kallikrein activity site in the collecting duct, and 2) KBP mRNA expression was significantly decreased in the kidney of SHR.

The relationship between the plasma potassium concentration and renal potassium excretion in the adrenalectomized rat

1987 ◽  
Vol 72 (5) ◽  
pp. 577-583 ◽  
Author(s):  
M. L. West ◽  
H. Sonnenberg ◽  
A. Veress ◽  
M. L. Halperin
Keyword(s):  
Collecting Duct ◽  
Plasma Osmolality ◽  
Plasma Potassium ◽  
Cortical Collecting Duct ◽  
Medullary Collecting Duct ◽  
Excretion Rates ◽  
The Relationship ◽  
Low K ◽  
Renal Potassium Excretion

1. The purpose of this study was to evaluate the renal mechanisms which lead to a high urine [K+] in adrenalectomized (ADX) rats devoid of aldosterone. 2. By dividing the urine [K+] by the urine to plasma osmolality ratio, the [K+] in the cortical collecting duct luminal fluid can be estimated; dividing this value by the plasma [K+] yields an index of the transtubular [K+] gradient (TTKG) in vivo. 3. The TTKG was close to 7 in aldosterone deficient ADX rats while on a normal K+ diet and fell towards unity when amiloride or a low K+ diet was administered to these rats. 4. With a longer time on a low K+ diet, the TTKG was less than 1 in ADX rats. This suggests that K+ was reabsorbed in the medullary collecting duct under these conditions. 5. Hyperkalemia appears to have an ‘aldosterone-like’ action in the cortical collecting duct in vivo in the absence of aldosterone in ADX rats. This action of hyperkalemia permits normal K+ excretion rates despite the absence of mineralocorticoids.

Increased AQP2 targeting in primary cultured IMCD cells in response to angiotensin II through AT1 receptor

2007 ◽  
Vol 292 (1) ◽  
pp. F340-F350 ◽  
Author(s):  
Yu-Jung Lee ◽  
In-Kyung Song ◽  
Kyung-Jin Jang ◽  
Jakob Nielsen ◽  
Jørgen Frøkiær ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Angiotensin Ii ◽  
Collecting Duct ◽  
Receptor Activation ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Water Reabsorption ◽  
Sprague Dawley Rats ◽  
Medullary Collecting Duct ◽  
Camp Levels

Vasopressin and angiotensin II (ANG II) play a major role in renal water and Na+ reabsorption. We previously demonstrated that ANG II AT1 receptor blockade decreases dDAVP-induced water reabsorption and AQP2 levels in rats, suggesting cross talk between these two peptide hormones ( Am J Physiol Renal Physiol 288: F673–F684, 2005). To directly address this issue, primary cultured inner medullary collecting duct (IMCD) cells from male Sprague-Dawley rats were treated for 15 min with 1) vehicle, 2) ANG II, 3) ANG II + the AT1 receptor blocker candesartan, 4) dDAVP, 5) ANG II + dDAVP, or 6) ANG II + dDAVP + candesartan. Immunofluorescence microscopy revealed that 10−8 M ANG II or 10−11 M dDAVP ( protocol 1) was associated with increased AQP2 labeling of the plasma membrane and decreased cytoplasmic labeling, respectively. cAMP levels increased significantly in response to 10−8 M ANG II and were potentiated by cotreatment with 10−11 M dDAVP. Consistent with this finding, immunoblotting revealed that this cotreatment significantly increased expression of phosphorylated AQP2. ANG II-induced AQP2 targeting was blocked by 10−5 M candesartan. In protocol 2, treatment with a lower concentration of dDAVP (10−12 M) or ANG II (10−9 M) did not change subcellular AQP2 distribution, whereas 10−12 M dDAVP + 10−9 M ANG II enhanced AQP2 targeting. This effect was inhibited by cotreatment with 10−5 M candesartan. ANG II-induced cAMP accumulation and AQP2 targeting were inhibited by inhibition of PKC activity. In conclusion, ANG II plays a role in the regulation of AQP2 targeting to the plasma membrane in IMCD cells through AT1 receptor activation and potentiates the effect of dDAVP on AQP2 plasma membrane targeting.

Collecting duct changes in potassium depletion: effects of ACE inhibition

1994 ◽  
Vol 266 (3) ◽  
pp. F419-F424 ◽  
Author(s):  
S. K. Mujais
Keyword(s):  
Collecting Duct ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Outer Diameter ◽  
Potassium Depletion ◽  
Sprague Dawley ◽  
Functional Changes ◽  
Pump Activity ◽  
Collecting Tubules ◽  
K Depletion

Potassium depletion is associated with a hyperreninemia that may be responsible for some of the renal hemodynamic and functional changes observed in K-deficient states. The present study was designed to evaluate whether interruption of the renin-angiotensin system with enalapril alters the collecting duct changes observed in K depletion. Adrenalectomized male Sprague-Dawley rats were allocated to either a normal (NK) or low-K diet (LK), and they either received enalapril or vehicle for 3 wk. Na:K pump activity (pmol.mm-1.h-1) in microdissected cortical collecting (CCT) and medullary collecting tubules (MCT) was determined at 21 days after group allocations. K depletion had a minimal effect on CCT outer diameter. In contrast, a marked hypertrophy was observed in the MCT diameter (91% increase, P < 0.001) that was significantly attenuated by enalapril treatment (56% increase, P < 0.001 vs. LK). An increase in Na:K pump activity was observed with LK, in the CCT from 497 +/- 47 to 1,089 +/- 83 (P < 0.001) and in the MCT from 489 +/- 36 to 1,396 +/- 45 pmol.mm-1.h-1 (P < 0.01). In K-replete rats, enalapril had no effect on Na:K pump activity in either CCT or MCT. Enalapril administration during LK had no effect on the increase in Na:K pump activity in the CCT (1,023 +/- 75 pmol.mm-1.h-1, P < 0.001), not different from LK alone. In the MCT, however, enalapril reduced the increment in Na:K pump activity induced by LK (1,116 +/- 39 pmol.mm-1.h-1, less than the change with LK alone).(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular morphology in outer medullary collecting duct: effect of 75% nephrectomy and K+ depletion

1992 ◽  
Vol 263 (6) ◽  
pp. F1119-F1127
Author(s):  
R. K. Zalups ◽  
D. A. Henderson
Keyword(s):  
Renal Mass ◽  
Morphological Changes ◽  
Collecting Duct ◽  
Fractional Excretion ◽  
Potassium Depletion ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Medullary Collecting Duct ◽  
Principal And Intercalated Cells ◽  
K Depletion

The present study was designed to determine, in rats, whether 75% nephrectomy and potassium depletion affect the principal and intercalated cells in the outer medullary collecting duct in the same manner as they affect the principal and intercalated cells in the cortical collecting duct. Ten days after a 75% reduction of renal mass, whole animal glomerular filtration rate decreased and the fractional excretion of potassium increased in rats. However, no morphological changes occurred in either the principal or intercalated cells of the outer medullary collecting duct after the reduction of renal mass. When 75% nephrectomized rats were placed on a diet deficient in potassium, the concentration of potassium in plasma and the absolute and fractional excretion of potassium decreased significantly. In addition, marked hypertrophy occurred in both the principal and intercalated cells in the outer medullary collecting duct. Previous findings from the same animals used in the present study show that 75% nephrectomy caused hypertrophic changes in principal cells of the cortical collecting duct, which could be inhibited by potassium depletion induced by the dietary restriction of potassium. The findings also show that the intercalated cells of the cortical collecting duct in 75% nephrectomized rats were unaffected by potassium depletion. On the basis of our findings, it appears there is an absence of hypertrophy in either the principal or intercalated cells in the outer medullary collecting duct of the rat after renal mass in the animal is reduced significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Conservation of Na+ vs. K+ by the rat cortical collecting duct

2011 ◽  
Vol 301 (1) ◽  
pp. F14-F20 ◽  
Author(s):  
Gustavo Frindt ◽  
Véronique Houde ◽  
Lawrence G. Palmer
Keyword(s):  
Collecting Duct ◽  
Immunoblot Analysis ◽  
Cortical Collecting Duct ◽  
Channel Activity ◽  
Distal Nephron ◽  
Whole Cell ◽  
Regulation Of Transport ◽  
Low K ◽  
Na Depletion ◽  
K Depletion

Regulation of transport by principal cells of the distal nephron contributes to maintenance of Na+ and K+ homeostasis. To assess which of these ions is given a higher priority by these cells, we investigated the upregulation of epithelial Na+ channels (ENaC) in the rat cortical collecting duct (CCD) during Na depletion with and without simultaneous K depletion. ENaC activity, assessed as whole cell amiloride-sensitive current in split-open tubules, was 260 ± 40 pA/cell in K-repleted but virtually undetectable (3 ± 1 pA/cell) in K-depleted animals. This difference was confirmed biochemically by the reduced amounts of the cleaved forms of both the α-ENaC and γ-ENaC subunits measured in immunoblots. In contrast, in K-depleted rats, simultaneously reducing Na intake did not affect the activity of ROMK channels, assessed as tertiapin-Q-sensitive whole cell currents, in the CCDs. The lack of Na current in K-depleted animals was the result of reduced levels of aldosterone in plasma, rather than a reduced sensitivity to the hormone. However, rats on a low-Na, low-K diet for 1 wk did not excrete more Na than those on a low-Na, control-K diet for the same period of time. Immunoblot analysis indicated increased levels of the thiazide-sensitive NaCl cotransporter and the apical Na-H exchanger NHE3. This suggests that with reduced K intake, Na balance is maintained despite reduced aldosterone and Na+ channel activity by upregulation of Na+ transport in upstream segments. Under these conditions, Na+ transport by the aldosterone-sensitive distal nephron is reduced, despite the low-Na intake to minimize K+ secretion and urinary K losses.

Effects of ET-1 on water and chloride transport in cortical collecting ducts of the rat

1993 ◽  
Vol 264 (4) ◽  
pp. F690-F696 ◽  
Author(s):  
K. Tomita ◽  
H. Nonoguchi ◽  
Y. Terada ◽  
F. Marumo
Keyword(s):  
Water Permeability ◽  
Continuous Flow ◽  
Chloride Transport ◽  
Collecting Duct ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Osmotic Water ◽  
Collecting Ducts ◽  
Medullary Collecting Duct

Endothelin-1 (ET-1) is known as a vasoconstrictor peptide. However, recent reports suggested the effects on the transport of renal tubule. We previously reported that ET-1 inhibited arginine vasopressin (AVP)-dependent adenosine 3',5'-cyclic monophosphate in rat collecting ducts. Physiologically, ET-1 reversibly and significantly inhibited AVP-stimulated water permeability in inner medullary collecting duct (IMCD). We therefore investigated the effects on water and electrolyte transport in rat cortical collecting ducts (CCD), where Na and Cl are actively reabsorbed more than in IMCD. Pathogen-free male Sprague-Dawley rats weighing 80-120 g were used after treatment with deoxycorticosterone pivalate for 1-2 wk. Isolated CCD were microperfused in vitro. The Cl concentration was measured by a continuous-flow ultra-microcolorimeter, and the raffinose concentration was measured as a volume marker by a continuous-flow ultra-microfluorometer. In the presence of 10(-9) M AVP, 10(-8) M ET-1 significantly inhibited fluid absorption (nl.mm-1 x min-1) from 0.25 +/- 0.02 to 0.15 +/- 0.05 (mean +/- SE, n = 6, P < 0.01), Cl absorption (pmol.mm-1 x min-1) from 30. 6 +/- 2.8 to 14.9 +/- 4.0 (P < 0.01), and potential difference (mV) from -5.4 +/- 1.3 to -4.0 +/- 1.2 (P < 0.01). Similar results were obtained in the lower concentration of 10(-10) M AVP and 10(-10) M ET-1. As for the osmotic water permeability (microns/s), 10(-8) M ET-1 significantly inhibited this from 320.1 +/- 50.9 to 202.1 +/- 42.2 (n = 7, P < 0.01) in the presence of 10(-9) M AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

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