Effects of diuretic drugs on Na, Cl, and K transport by rat renal distal tubule

1986 ◽  
Vol 250 (6) ◽  
pp. F1013-F1023 ◽  
Author(s):  
H. Velazquez ◽  
F. S. Wright
Keyword(s):  
Sodium Transport ◽  
Rat Kidney ◽  
Distal Tubule ◽  
Cell Types ◽  
Sodium Absorption ◽  
Thick Ascending Limb ◽  
Chloride Absorption ◽  
Diuretic Drugs ◽  
Potassium Secretion

Diuretic drugs were used to characterize mechanisms involved in transporting sodium, chloride, and potassium across the wall of surface distal tubules of the rat kidney using in vivo microperfusion techniques. Both furosemide and chlorothiazide inhibited sodium and chloride absorption but did not affect the rate of potassium secretion or the transepithelial voltage. However, chlorothiazide inhibited sodium and chloride absorption more completely than furosemide and was additive to the effect of furosemide; furosemide was ineffective if chlorothiazide was already present. In contrast to the effect of furosemide, bumetanide did not affect sodium and chloride absorption but did increase potassium secretion. Amiloride reduced sodium absorption and potassium secretion without affecting net chloride absorption. These effects were additive to those of chlorothiazide. In the loop of Henle bumetanide was more effective than furosemide in inhibiting net sodium potassium and chloride absorption. It appears that cells of the distal tubule in the rat possess an Na-Cl cotransport mechanism that differs from the Na-K-2Cl cotransport mechanism found in the thick ascending limb. Sodium transport also proceeds via a conductive pathway that is inhibited by amiloride. The two modes of sodium transport, conductive and coupled to chloride, may occur in different cell types along the distal tubule.

Thiazide-sensitive sodium chloride cotransport in early distal tubule

1987 ◽  
Vol 253 (3) ◽  
pp. F546-F554 ◽  
Author(s):  
D. H. Ellison ◽  
H. Velazquez ◽  
F. S. Wright
Keyword(s):  
Sodium Transport ◽  
Chloride Transport ◽  
Collecting Duct ◽  
Distal Tubule ◽  
Sodium Absorption ◽  
Transport Pathways ◽  
Luminal Membrane ◽  
Chloride Absorption ◽  
Distal Tubules

At least two pathways mediate sodium absorption across the luminal membrane of the renal distal tubule. One pathway is a conductive channel and the other appears to be a coupled Na-Cl cotransport pathway. The distal tubule comprises three segments: the distal convoluted tubule, the connecting tubule, and the initial collecting duct. To provide information about cellular locations of the proposed sodium transport pathways, we perfused early (14-38% of whole distal length) and late (61-83% of whole distal length) segments of whole distal tubules separately in vivo in anesthetized rats. When perfused with a solution that resembles fluid normally arriving at the distal tubule (75 mM Na, 68 mM Cl), rates of sodium absorption were similar in early and late segments (early 68 +/- 29.6, late 67 +/- 27.5 pmol X min-1 X mm-1). When perfused with a solution that resembles interstitial fluid (148 mM Na, 110 mM Cl), sodium transport was significantly higher in early than in late segments (276 +/- 28.4 vs. 113 +/- 29.7 pmol X min-1 X mm-1). Chlorothiazide (10(-3) M), which blocks sodium and chloride absorption in whole distal tubules, reduced sodium and chloride transport to zero in early distal tubules but had no significant effect in late distal tubules. Removing all chloride from perfusion solutions reduced sodium transport in early but not late distal segments.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals In vivo nuclear translocation of mineralocorticoid and glucocorticoid receptors in rat kidney: differential effect of corticosteroids along the distal tubule

2010 ◽  
Vol 299 (6) ◽  
pp. F1473-F1485 ◽  
Author(s):  
Daniel Ackermann ◽  
Nikolay Gresko ◽  
Monique Carrel ◽  
Dominique Loffing-Cueni ◽  
Daniel Habermehl ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Glucocorticoid Receptors ◽  
Nuclear Translocation ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Distal Tubule ◽  
Plasma Aldosterone ◽  
Thick Ascending Limb ◽  
Cell Nuclei

Aldosterone and corticosterone bind to mineralocorticoid (MR) and glucocorticoid receptors (GR), which, upon ligand binding, are thought to translocate to the cell nucleus to act as transcription factors. Mineralocorticoid selectivity is achieved by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) that inactivates 11β-hydroxy glucocorticoids. High expression levels of 11β-HSD2 characterize the aldosterone-sensitive distal nephron (ASDN), which comprises the segment-specific cells of late distal convoluted tubule (DCT2), connecting tubule (CNT), and collecting duct (CD). We used MR- and GR-specific antibodies to study localization and regulation of MR and GR in kidneys of rats with altered plasma aldosterone and corticosterone levels. In control rats, MR and GR were found in cell nuclei of thick ascending limb (TAL), DCT, CNT, CD cells, and intercalated cells (IC). GR was also abundant in cell nuclei and the subapical compartment of proximal tubule (PT) cells. Dietary NaCl loading, which lowers plasma aldosterone, caused a selective removal of GR from cell nuclei of 11β-HSD2-positive ASDN. The nuclear localization of MR was unaffected. Adrenalectomy (ADX) resulted in removal of MR and GR from the cell nuclei of all epithelial cells. Aldosterone replacement rapidly relocated the receptors in the cell nuclei. In ASDN cells, low-dose corticosterone replacement caused nuclear localization of MR, but not of GR. The GR was redistributed to the nucleus only in PT, TAL, early DCT, and IC that express no or very little 11β-HSD2. In ASDN cells, nuclear GR localization was only achieved when corticosterone was replaced at high doses. Thus ligand-induced nuclear translocation of MR and GR are part of MR and GR regulation in the kidney and show remarkable segment- and cell type-specific characteristics. Differential regulation of MR and GR may alter the level of heterodimerization of the receptors and hence may contribute to the complexity of corticosteroid effects on ASDN function.

Mutual dependence of sodium and chloride absorption by renal distal tubule

1984 ◽  
Vol 247 (6) ◽  
pp. F904-F911 ◽  
Author(s):  
H. Velazquez ◽  
D. W. Good ◽  
F. S. Wright
Keyword(s):  
Chloride Transport ◽  
Chloride Concentration ◽  
Distal Tubule ◽  
Sodium Concentration ◽  
Sodium Absorption ◽  
Similar Extent ◽  
Luminal Membrane ◽  
Chloride Absorption ◽  
Transepithelial Voltage

Sodium transport and chloride transport by the renal distal tubule of rats were studied by in vivo continuous microperfusion to determine the effects of separately altering luminal sodium and chloride concentrations. Results showed that sodium absorption depends on luminal sodium concentration and chloride absorption depends on luminal chloride concentration; both relations are linear between approximately 10 and 100 mM and have slopes of approximately 2.5 pmol X min-1 X mM-1. Sodium absorption is also a saturable function of luminal chloride concentration, and chloride absorption is a saturable function of luminal sodium concentration; the half-maximal chloride and sodium concentrations are approximately 10 mM. Furosemide, 10(-4) M, when added to the fluid used to perfuse this segment inhibited sodium absorption and chloride absorption to a similar extent. Removal of chloride from luminal fluid (replaced with sulfate) and addition of furosemide to the perfusion fluid had little or no effect on the measured transepithelial voltage. The results are consistent with the presence of a mechanism in the luminal membrane of distal tubule cells that couples the absorptive transport of sodium and chloride.

Sodium and chloride transport in the large intestine of potassium-loaded rats

1986 ◽  
Vol 251 (2) ◽  
pp. G249-G252 ◽  
Author(s):  
M. E. Budinger ◽  
E. S. Foster ◽  
J. P. Hayslett ◽  
H. J. Binder
Keyword(s):  
Chloride Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Ringer Solution ◽  
Sodium Absorption ◽  
Chloride Absorption ◽  
Dietary Potassium ◽  
Potassium Secretion ◽  
Potassium Loading

Increased dietary potassium ("potassium loading") induces several adaptive changes in colonic function, including increased potential-dependent potassium secretion, active potassium secretion, and Na-K-ATPase activity, but does not alter net sodium absorption in vivo. To establish whether potassium loading stimulates active sodium transport, unidirectional, net sodium, and chloride fluxes were determined under voltage-clamp conditions across isolated rat distal colonic mucosa. In normal animals net sodium flux (JNanet), net chloride flux (JClnet) and short-circuit current (Isc) were 6.1 +/- 1.1, 8.4 +/- 1.0, and 0.7 +/- 0.1 mu eq X h-1. cm-2, respectively; potassium loading significantly increased JNanet and Isc by 4.9 +/- 1.4 and 3.5 +/- 0.7 mu eq X h-1 X cm-2, respectively, without changing JClnet. Amiloride (0.1 mM) inhibited the increases in JNanet and Isc produced by potassium loading. In Cl-free Ringer solution in normal animals JNanet was reduced to 0.6 +/- 0.3 mu eq X h-1 X cm-2. Potassium loading produced identical increases in JNanet and Isc, which were also completely inhibited by 0.1 mM amiloride. These studies establish that potassium loading induces amiloride-sensitive electrogenic sodium absorption without affecting electroneutral sodium-chloride absorption.

Localization and regulation of the rat renal Na(+)-K(+)-2Cl- cotransporter, BSC-1

1996 ◽  
Vol 271 (3) ◽  
pp. F619-F628 ◽  
Author(s):  
C. A. Ecelbarger ◽  
J. Terris ◽  
J. R. Hoyer ◽  
S. Nielsen ◽  
J. B. Wade ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Rat Colon ◽  
Thick Ascending Limb ◽  
Outer Medulla ◽  
Water Excretion ◽  
Saline Loading ◽  
Cloned Cdna ◽  
Urinary Concentrating Ability

To investigate the role of the thick ascending limb (TAL) Na(+)-K(+)-2Cl- cotransporter in regulation of water excretion, we have prepared a peptide-derived polyclonal antibody based on the cloned cDNA sequence of the rat type 1 bumetanide-sensitive cotransporter, BSC-1 (also termed "NKCC-2"). Immunoblots revealed a single broad 161-kDa band in membrane fractions of rat renal outer medulla and cortex but not from rat colon or parotid gland. A similar protein was labeled in mouse kidney. Immunoperoxidase immunohistochemistry in rat kidney revealed labeling restricted to the medullary and cortical TAL segments. Because long-term regulation of urinary concentrating ability may depend on regulation of Na(+)-K(+)-2Cl- cotransporter abundance, we used immunoblotting to evaluate the effects of several in vivo factors on expression levels of BSC-1 protein in rat kidney outer medulla. Chronic oral saline loading with 0.16 M NaCl markedly increased BSC-1 abundance. However, long-term vasopressin infusion or thirsting of rats did not affect BSC-1 abundance. Chronic furosemide infusion caused a 9-kDa upward shift in apparent molecular mass and an apparent increase in expression level. These results support the previous identification of BSC-1 as the TAL Na(+)-K(+)-2Cl- transporter and demonstrate that the expression of this transporter is regulated.

α2-Adrenergic-mediated tubular NO production inhibits thick ascending limb chloride absorption

2001 ◽  
Vol 281 (4) ◽  
pp. F679-F686 ◽  
Author(s):  
Craig F. Plato ◽  
Jeffrey L. Garvin
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Chloride Transport ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
No Production ◽  
Thick Ascending Limb ◽  
Chloride Absorption ◽  
Ly 83583

Stimulation of α2-adrenergic receptors inhibits transport in various nephron segments, and the thick ascending limb of the loop of Henle (THAL) expresses α2-receptors. We hypothesized that selective α2-receptor activation decreases NaCl absorption by cortical THALs through activation of NOS and increased production of NO. We found that the α2-receptor agonist clonidine (10 nM) decreased chloride flux ( J Cl) from 119.5 ± 15.9 to 67.4 ± 13.8 pmol · mm−1 · min−1 (43% reduction; P < 0.02), whereas removal of clonidine from the bath increased J Cl by 20%. When NOS activity was inhibited by pretreatment with 5 mM N G-nitro-l-arginine methyl ester, the inhibitory effects of clonidine on THAL J Clwere prevented (81.7 ± 10.8 vs. 71.6 ± 6.9 pmol · mm−1 · min−1). Similarly, when the NOS substrate l-arginine was deleted from the bath, addition of clonidine did not decrease THAL J Cl from control (106.9 ± 11.6 vs. 132.2 ± 21.3 pmol · mm−1 · min−1). When we blocked the α2-receptors with rauwolscine (1 μM), we found that the inhibitory effect of 10 nM clonidine on THAL J Cl was abolished, verifying that α2, rather than I1, receptors mediate the effects of clonidine in the THAL. We investigated the mechanism of NOS activation and found that intracellular calcium concentration did not increase in response to clonidine, whereas pretreatment with 150 nM wortmannin abolished the clonidine-mediated inhibition of THAL J Cl, indicating activation of phosphatidylinositol 3-kinase and the Akt pathway. We found that pretreatment of THALs with 10 μM LY-83583, an inhibitor of soluble guanylate cyclase, blocked clonidine-mediated inhibition of THAL J Cl. In conclusion, α2-receptor stimulation decreases THAL J Cl by increasing NO release and stimulating guanylate cyclase. These data suggest that α2-receptors act as physiological regulators of THAL NO synthesis, thus inhibiting chloride transport and participating in the natriuretic and diuretic effects of clonidine in vivo.

Stimulation of distal potassium secretion by low lumen chloride in the presence of barium

1985 ◽  
Vol 248 (5) ◽  
pp. F638-F649 ◽  
Author(s):  
D. H. Ellison ◽  
H. Velazquez ◽  
F. S. Wright
Keyword(s):  
Chloride Concentration ◽  
Distal Tubule ◽  
Perfusion Fluid ◽  
Transport Pathway ◽  
Luminal Membrane ◽  
Potassium Secretion ◽  
Transepithelial Voltage ◽  
Tubule Fluid ◽  
Stimulation Of

Potassium secretion into the renal distal tubule is increased when chloride in the tubule fluid is replaced by another anion. The present experiments were done to determine whether this increment in transported potassium traverses a conductive pathway from cell to lumen. Transport rates of potassium, sodium, chloride, and fluid by the renal distal tubule of rats were examined in vivo by continuous microperfusion. The effects of substituting gluconate for chloride in the presence and absence of 5 mM barium in the perfusion fluid were determined. When gluconate replaced chloride in the perfusion solutions, potassium secretion increased (by 44%) without a significant change in transepithelial voltage. Barium in the lumen increased the magnitude of the lumen-negative transepithelial voltage (by 30%) and reduced potassium secretion (by 56%) by inhibiting conductive potassium movement. Barium also decreased both sodium (by 51%) and chloride (by 37%) absorption. Barium did not reduce the stimulation of potassium secretion caused by reducing lumen chloride concentration. Potassium secretion increased (by 77%) when lumen chloride was reduced in the presence of 5 mM barium. We interpret these results by postulating that a cotransport mechanism linking potassium and chloride is present in the luminal membrane of distal tubule cells, that this mechanism operates in parallel with a conductive transport pathway for potassium, and that the K-Cl cotransport mechanism is not inhibited by barium.

Unidirectional potassium fluxes in renal distal tubule: effects of chloride and barium

1986 ◽  
Vol 250 (5) ◽  
pp. F885-F894 ◽  
Author(s):  
D. H. Ellison ◽  
H. Velazquez ◽  
F. S. Wright
Keyword(s):  
Secretory Pathway ◽  
Chloride Concentration ◽  
Distal Tubule ◽  
Blocking Agent ◽  
Sprague Dawley ◽  
Potassium Permeability ◽  
Potassium Flux ◽  
Potassium Secretion ◽  
The Difference

Low luminal concentrations of chloride stimulate net potassium secretion by the renal distal tubule, independent of changes in transepithelial voltage. These effects are not prevented by the luminal application of the potassium channel blocking agent barium. Because net potassium secretion comprises secretory and absorptive components, we sought to evaluate the effects of chloride and barium on unidirectional potassium fluxes in the renal distal tubule. In vivo microperfusion methods were used in anesthetized Sprague-Dawley rats. Perfusion solutions contained either 42K or 86Rb as tracers for potassium. Tracer efflux coefficients, indicating apparent potassium permeability, were similar when measured using either isotope. Net potassium flux was determined as the difference between perfusion and collected rate, and unidirectional absorptive potassium flux was calculated as the product of the mean luminal potassium concentration and the tracer efflux coefficient. During perfusion with a solution that resembled fluid normally arriving at the early distal tubule, the absorptive potassium flux was approximately 25% of the unidirectional secretory flux. Reducing lumen chloride concentration increased net potassium secretion, because blood-to-lumen potassium flux increased from 61 +/- 12.7 to 96 +/- 14.6 pmol/min. Barium reduced both absorptive and secretory fluxes but did not prevent the stimulation of net potassium secretion that occurs when luminal chloride concentration is reduced. Apparent potassium permeability during perfusion with a solution that resembled fluid normally arriving at the early distal tubule was 800 nm/s when corrected for voltage. Together with the results of previous experiments, these results are consistent with the presence of a secretory pathway linking potassium with chloride in the luminal membrane of cells of the distal tubule.

Water and electrolyte transport by rabbit esophagus

1975 ◽  
Vol 229 (2) ◽  
pp. 438-443 ◽  
Author(s):  
DW Powell ◽  
SM Morris ◽  
DD Boyd
Keyword(s):  
Sodium Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Electrolyte Transport ◽  
Potential Difference ◽  
Sodium Absorption ◽  
Bathing Solution ◽  
Electrical Potential Difference

The nature of the transmural electrical potential difference and the characteristics of water and electrolyte transport by rabbit esophagus were determined with in vivo and in vitro studies. The potential difference of the perfused esophagus in vivo was -28 +/- 3 mV (lumen negative). In vitro the potential difference was -17.9 +/- 0.6 mV, the short-circuit current 12.9 +/- 0.6 muA/cm2, and the resistance 1,466 +/- 43 ohm-cm2. Net mucosal-to-serosal sodium transport from Ringer solution in the short-circuited esophagus in vitro accounted for 77% of the simultaneously measured short-circuit current and net serosal-to-mucosal chloride transport for 14%. Studies with bicarbonate-free, chloride-free, and bicarbonate-chloride-free solutions suggested that the net serosal-to mucosal transport of these two anions accounts for the short-circuit current not due to sodium absorption. The potential difference and short-circuit current were saturating functions of bathing solution sodium concentration and were inhibited by serosal ouabain and by amiloride. Thus active mucosal-to-serosal sodium transport is the major determinant of the potential difference and short-circuit current in this epithelium.

Luminal influences on potassium secretion: sodium concentration and fluid flow rate

1979 ◽  
Vol 236 (2) ◽  
pp. F192-F205 ◽  
Author(s):  
D. W. Good ◽  
F. S. Wright
Keyword(s):  
Fluid Flow ◽  
Flow Rate ◽  
Distal Tubule ◽  
Sodium Concentration ◽  
Fluid Flow Rate ◽  
Physiological Range ◽  
Luminal Flow ◽  
Potassium Secretion ◽  
K Concentration

Two methods of in vivo continuous microperfusion were used to evaluate separately luminal sodium concentration and fluid flow rate as factors regulating potassium secretion by the renal distal tubule of the rat. Emphasis was placed on evaluating changes in sodium concentration (43-97 mM) and flow rate (4-27 nl/min) within the physiological range. Absolute rates of Na, K, Cl, and H2O transport were measured. Results showed that increasing early distal flow rate without increasing early distal Na concentration significantly increased the absolute rate of potassium secretion by the distal tubule. In contrast, increasing early distal Na concentration, distal Na delivery, and distal Na absorption did not affect potassium secretion if flow rate was not changed. Further studies showed that reducing early distal Na concentration below the physiological range (to 15 mM) caused the direction of net sodium transport to be reversed but did not significantly reduce potassium secretion. Increasing early distal K concentration (to 34 mM) caused the direction of net potassium transport to be reversed. The rate of potassium secretion appears to depend in part on the luminal potassium concentration. Increases in luminal flow rate may increase the rate of potassium secretion by lowering the luminal K concentration.

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