Effects of spironolactone and amiloride on corticosteroid-induced changes in colonic function

1981 ◽  
Vol 241 (4) ◽  
pp. G300-G305
Author(s):  
A. N. Charney ◽  
J. Wallach ◽  
S. Ceccarelli ◽  
M. Donowitz ◽  
C. L. Costenbader
Keyword(s):  
Atpase Activity ◽  
Water Absorption ◽  
Sodium Transport ◽  
Transport Processes ◽  
Potential Difference ◽  
Pentobarbital Sodium ◽  
Electrolyte Absorption ◽  
Potassium Secretion ◽  
Induced Changes

Mineralocorticoid and glucocorticoid effects on colonic electrolyte absorption were compared by examining the alterations caused by spironolactone and amiloride in corticosteroid-treated rats. Animals were treated for 3 days with deoxycorticosterone acetate (DOCA; 0.5 mg . 100 g-1 . day-1), methylprednisolone (MP; 3 or 0.5 mg . 100 g-1 . day), and spironolactone (14 mg . 100 g-1 . day-1 im) singly or in combination. On day 4, rats were anesthetized with pentobarbital sodium and perfused in vivo with Ringer-HCO3 solution. Both doses of MP and DOCA increased net colonic sodium and water absorption and mucosal Na-K-ATPase activity. Concurrent spironolactone treatment completely prevented these effects in DOCA-treated rats but had no effect in MP-treated rats. Untreated, MP-treated, and DOCA-treated animals were perfused with a Ringer-HCO3 solution containing 1 mM amiloride. Amiloride reduced net colonic sodium and water absorption, transmural potential difference, and potassium secretion in all rats by approximately 55%. These effects were almost immediate and completely reversible. These findings in the rat suggest that 1) different receptors mediate the colonic effects of mineralocorticoids and glucocorticoids and 2) these corticosteroids do not differ in their relative effects on amiloride-sensitive and amiloride-resistant colonic sodium transport processes.

Effect of cycloheximide on corticosteroid-induced changes in colonic function

1982 ◽  
Vol 243 (2) ◽  
pp. G112-G116
Author(s):  
A. N. Charney ◽  
J. D. Wallach ◽  
M. Donowitz ◽  
N. Johnstone
Keyword(s):  
Atpase Activity ◽  
Water Absorption ◽  
Specific Activity ◽  
Potential Difference ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Glucocorticoid Treatment ◽  
Chloride Absorption ◽  
Induced Changes ◽  
Glucocorticoid Action

Chronic parenteral mineralocorticoid and glucocorticoid treatment increases colonic sodium and water absorption and mucosal Na-K-ATPase activity. Cycloheximide, a protein synthesis inhibitor, was utilized to compare the mechanisms of action of these corticosteroids. Rats were injected with 50 or 100 micrograms/100 g body wet cycloheximide every 12 h, 0.5 or 3 mg/100 g deoxycorticosterone (DOCA) daily, or 3 mg/100 g methylprednisolone (MP) daily, singly or in combination for 2 days. In water absorption, transmural potential difference, and the specific activity of Na-K-ATPase were measured. Cycloheximide alone did not alter colonic water, sodium, or chloride absorption or Na-K-ATPase activity but did increase transmural potential difference. DOCA-induced increases in colonic absorption and Na-K-ATPase were completely prevented by cycloheximide. Cycloheximide completely prevented the increase in Na-K-ATPase in MP-treated rats but only partially reduced the MP-induced increase in sodium and water absorption. These results suggest that this enzyme is not the primary site of glucocorticoid action. It remains to be determined whether an increase in Na-K-ATPase activity is a necessary part of the maximal colonic response to chronic glucocorticoid treatment.

Evidence that aldosterone influences transport in target tissues by dissimilar mechanisms

1985 ◽  
Vol 248 (4) ◽  
pp. F507-F512 ◽  
Author(s):  
D. Hirsch ◽  
P. Pace ◽  
H. J. Binder ◽  
J. P. Hayslett
Keyword(s):  
Distal Colon ◽  
Proximal Colon ◽  
Potassium Transport ◽  
Potential Difference ◽  
Sodium Absorption ◽  
Potassium Secretion ◽  
Secondary Hyperaldosteronism ◽  
Induced Changes ◽  
Sodium And Potassium

The present study was performed to answer the question: Is the action of aldosterone on electrolyte transport and electrical properties similar in all target tissues? Studies were performed in vivo in control animals and rats with secondary hyperaldosteronism, caused by a sodium-free diet, to compare the effects of hyperaldosteronism on distal colon with hormone-induced changes in proximal colon. In distal colon aldosterone increased net sodium absorption and potassium secretion approximately threefold. Transmural potential difference increased from -15 +/- 2 to -83 +/- 3 mV (lumen negative) and ISC rose from 167 +/- 26 to 1,023 +/- 17 microA X cm-2. These aldosterone-induced responses were completely inhibited by 0.1 mM amiloride. In contrast, in proximal colon potential difference was unchanged or increased slightly in experimental animals and ISC increased only 28% above control, although increases in net sodium and potassium transport were similar to changes observed in distal colon. Amiloride did not reduce sodium absorption in proximal colon of animals with hyperaldosteronism; ISC was decreased by 43%. These studies demonstrate that rat proximal colon is an aldosterone-sensitive tissue, but that the mechanism by which aldosterone influences sodium transport is not identical in distal and proximal portions of colon.

Role of glucocorticoids and aldosterone in maintenance of colonic cation transport

1980 ◽  
Vol 238 (3) ◽  
pp. F181-F186 ◽  
Author(s):  
C. P. Bastl ◽  
H. J. Binder ◽  
J. P. Hayslett
Keyword(s):  
Water Absorption ◽  
Marked Reduction ◽  
Cation Transport ◽  
Potential Difference ◽  
Regulatory Control ◽  
Sodium Absorption ◽  
Potassium Secretion ◽  
Adrenalectomized Rats

Adrenalectomized rats were maintained on physiologic replacement doses of aldosterone or dexamethasone for 24 h after adrenalectomy. Net cation movement and transmural potential difference were determined during in vivo perfusion of the colon. Adrenalectomy without replacement steroids resulted in marked reduction of sodium and water absorption, potassium secretion, and transmural potential difference (PD). Aldosterone 10 microgram . 100 g body wt-1 . 24 h-1 significantly increased net potassium secretion above adrenalectomized levels but did not restore transport to control levels. Sodium and water absorption and transmural PD were not affected. Aldosterone 30 microgram . 100 g body wt-1 . 24 h-1 increased but did not restore net movement of sodium or potassium to control levels. In contrast to aldosterone, physiologic amounts of dexamethasone, 10 microgram . 100 g body wt-1 . 24 h-1, preserved normal electrolyte movement and electrical properties in adrenalectomized rats. In additional experiments the aldosterone antagonist spironolactone was administered for 3 days to rats with intact adrenal function. Net sodium absorption fell only 22% below control with insigificant decreases in potassium secretion and transmural PD. These data suggest that glucocorticoid hormones exert regulatory control of basal colonic fluid and electrolyte function.

Potassium secretion by nasal salt glands of desert lizard Sauromalus obesus

1987 ◽  
Vol 253 (1) ◽  
pp. R83-R90 ◽  
Author(s):  
T. J. Shuttleworth ◽  
J. L. Thompson ◽  
W. H. Dantzler
Keyword(s):  
Atpase Activity ◽  
Intraperitoneal Injection ◽  
Salt Gland ◽  
Salt Glands ◽  
Fourfold Increase ◽  
Gland Weight ◽  
Desert Lizard ◽  
Potassium Secretion ◽  
Sauromalus Obesus

Potassium secretion by the nasal salt glands of the herbivorous desert lizard Sauromalus obesus was determined in vivo by a new technique. Intraperitoneal injection of KCl rapidly increased the potassium secretion rate from 0.28 to 15.35 mumol X 100 g-1 X h-1. A second identical intraperitoneal injection, given 15 h after the first, further increased potassium secretion to 50.09 mumol X 100 g-1 X h-1. This was associated with a doubling of plasma K+ concentration and salt gland Na+-K+-adenosinetriphosphatase (ATPase) activity. Neither salt gland weight or residual (Mg2+) ATPase activity were affected. In an isolated perfused head preparation, potassium secretion from the nasal salt glands was stimulated from 0.99 to 10.76 mumol X 100 g-1 X h-1 by methacholine and to 14.68 mumol X 100 g-1 X h-1 by forskolin. In this perfused preparation, simultaneous determination of salt gland perfusion flow (using radiolabeled microspheres) and the rate of potassium secretion revealed that the secreting glands removed 68% of the perfusing potassium ions. Calculations indicated that secretion at the maximal rate observed in vivo would necessitate a fourfold increase in the rate of blood flow to the gland.

Increase of lung sodium-potassium-ATPase activity during recovery from high-permeability pulmonary edema

1996 ◽  
Vol 271 (6) ◽  
pp. L896-L909 ◽  
Author(s):  
D. Zuege ◽  
S. Suzuki ◽  
Y. Berthiaume
Keyword(s):  
Atpase Activity ◽  
Pulmonary Edema ◽  
Sodium Transport ◽  
Sodium Ion ◽  
Type Ii ◽  
Active Sodium ◽  
Sodium Potassium ◽  
Sodium Ion Transport ◽  
Active Sodium Transport

Previous studies have suggested that recovery from pulmonary edema may be dependent on active sodium ion transport. Most of the data supporting this concept came from work done in isolated type II cells, isolated lung preparations, or in models of alveolar flooding. There is a limited amount of information regarding the role of active sodium ion transport in vivo. Furthermore, most of this information was obtained in one model of pulmonary edema, the hyperoxic lung injury model. The purpose of these experiments was then to measure the activity of the sodium-potassium-adenosinetriphosphatase (Na(+)-K(+)-ATPase), the active component of the sodium transport process and an indirect marker of active sodium transport, during recovery from thiourea-induced pulmonary edema in rats. Na(+)-K(+)-ATPase activity was significantly increased during recovery from lung edema. This increase could not be accounted for by the Na(+)-K(+)-ATPase activity present in inflammatory cells recruited in the lung by the injury process or by a direct impact of thiourea on the enzyme. Alveolar flooding, induced by instillation of a protein-containing solution into the airways of ventilated rats also increased the activity of Na(+)-K(+)-ATPase, suggesting that activation of the enzyme is probably secondary to either the presence of edema or the physiological consequences associated with edema. The quantity of lung Na(+)-K(+)-ATPase protein was also elevated during edema resolution, indicating that augmented synthesis of this enzyme underlies the increased enzyme activity observed. The quantity of Na(+)-K(+)-ATPase protein in alveolar type II cells was also significantly enhanced during recovery from edema, suggesting that these cells contribute to active sodium transport in vivo. The results of this study suggest that active sodium transport could participate in the resolution of pulmonary edema.

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.

Hypoxia reversibly inhibits epithelial sodium transport but does not inhibit lung ENaC or Na-K-ATPase expression

2003 ◽  
Vol 284 (1) ◽  
pp. L77-L83 ◽  
Author(s):  
Todd C. Carpenter ◽  
Stacey Schomberg ◽  
Christopher Nichols ◽  
Kurt R. Stenmark ◽  
John V. Weil
Keyword(s):  
Atpase Activity ◽  
Sodium Transport ◽  
Airway Epithelial ◽  
Epithelial Sodium Channels ◽  
Adult Rats ◽  
Lung Epithelial ◽  
Nasal Potential Difference ◽  
Baseline Levels ◽  
Alveolar Liquid Clearance

Hypoxia reduces alveolar liquid clearance and the nasal potential difference, a marker of airway epithelial sodium transport. The mechanisms underlying this impaired epithelial sodium transport in vivo remain uncertain. We hypothesized that epithelial sodium transport impaired by hypoxia would recover quickly with reoxygenation and that hypoxia decreases the expression of lung epithelial sodium channels and Na,K-ATPases. We studied adult rats exposed to normoxia, hypoxia (Fi O2 = 0.1) for 24 h, or hypoxia followed by recovery in normoxia. Nasal potential differences decreased by 40% with hypoxia ( P < 0.001), returning to baseline levels with reoxygenation. Lung Na,K-ATPase activity decreased by 40% with hypoxia ( P = 0.003), recovering to baseline levels with reoxygenation. Lung expression of mRNA encoding for epithelial sodium channel (ENaC)-α, -β, and -γ or for Na,K-ATPase-α1 did not change significantly with hypoxia or recovery nor did lung expression of ENaC-α, ENaC-β, Na,K-ATPase-α1, or Na,K-ATPase-β1 protein. We conclude that subacute exposure to moderate hypoxia reversibly impairs airway epithelial sodium transport and lung Na,K-ATPase activity but that those changes are not due to changes in the lung expression of sodium-transporting proteins.

Aldosterone in colonic potassium adaptation in rats

1988 ◽  
Vol 117 (3) ◽  
pp. 379-386 ◽  
Author(s):  
C. J. Edmonds ◽  
C. L. Willis
Keyword(s):  
Sodium Transport ◽  
Plasma Potassium ◽  
Replacement Treatment ◽  
Potassium Adaptation ◽  
Complete Adaptation ◽  
Potassium Secretion ◽  
Potassium Loading ◽  
Adrenalectomized Rats ◽  
Intact Rats

ABSTRACT The influence of adrenalectomy and administration of aldosterone on potassium secretion by colonic epithelium was studied in vivo in rats, particularly in relation to potassium adaptation (induced by feeding a potassium-rich diet) and the response to acute i.v. administration of a potassium load. Adrenalectomy (rats maintained on dexamethasone and saline) impaired the development of potassium adaptation or considerably reduced it if the rats had been previously adapted. The partial adaptation observed in the adrenalectomized rats may be related to the increased plasma potassium concentration developed when these rats received the potassium-rich diet. Within 2 h of acute aldosterone administration, the response of the potassium secretion rate to acute potassium loading in adrenalectomized rats was significantly improved. When aldosterone (2 μg/day per 100 g body weight, given by osmotic minipump) was added to the replacement treatment, the plasma concentration of potassium was similar to that of the intact rats, and both potassium adaptation and the response to the acute potassium load were completely restored. Transepithelial potential difference and sodium transport were not stimulated, being similar to the values in intact rats. Considerable changes in potassium secretion induced by acute potassium loading did not significantly affect sodium transport. The findings suggest that the sodium and potassium epithelial pathways are, to a large extent, independently influenced by aldosterone. Aldosterone appears to be essential for complete adaptation and, in a relatively low dose, can completely restore potassium adaptation and the response to acute potassium loads in adrenalectomized rats. J. Endocr. (1988) 117, 379–386

Glucocorticoid stimulation of Na-K-ATPase in superfused distal segments of kidney tubules in vitro

1982 ◽  
Vol 243 (5) ◽  
pp. F463-F470 ◽  
Author(s):  
B. M. Rayson ◽  
I. S. Edelman
Keyword(s):  
Atpase Activity ◽  
Time Course ◽  
Rat Kidney ◽  
Maximal Effect ◽  
Kidney Tubules ◽  
Response Data ◽  
The One ◽  
Induced Changes

The ability of glucocorticoids to regulate Na-K-ATPase activity directly was assessed in separated rat kidney tubules derived from the distal nephron. These tubules were superfused under sterile conditions and maintained in a viable condition for at least 24 h in a newly devised apparatus. Viability was assessed by measuring O2 consumption, protein/DNA ratios, and Na-K-ATPase and Mg-ATPase activities. At a concentration of 10(-8) M, dexamethasone elicited a 27% increase in tubular Na-K-ATPase activity in 6 h and a 32% increase in 24 h. In a separate series, assayed at 24 h, the maximal effect was obtained at a dexamethasone concentration of less than 10(-8) M, and by inspection half-maximal stimulation was obtained at approximately 10(-9) M. At a concentration of 10(-7) M, 17 beta-estradiol, testosterone, progesterone, and deoxycorticosterone acetate had no significant effect on tubular Na-K-ATPase activity. These results as well as the time-course and dose-response data imply that the response is mediated by the glucocorticoid receptor pathway. Since the magnitude of response in vitro was similar to the one obtained after injection of dexamethasone in vivo, much if not all of the action appears to be direct and independent of glucocorticoid-induced changes in the filtered Na+ load.

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.

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