Pathogenesis of Salt Retention in Dogs with Chronic Bile-Duct Ligation

1982 ◽  
Vol 62 (1) ◽  
pp. 65-70 ◽  
Author(s):  
C. Chaimovitz ◽  
U. Alon ◽  
O. S. Better
Keyword(s):  
Bile Duct ◽  
Sodium Excretion ◽  
Control Period ◽  
Extracellular Volume ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Sodium Balance ◽  
Sodium Retention ◽  
Plasma Aldosterone Concentration ◽  
Duct Ligation

1. The present study investigates the role of mineralocorticoids in the pathogenesis of salt retention and ascites in dogs with chronic ligation of the common bile duct (CBDL). 2. After CBDL the natriuretic response to an intravenous sodium load [0.9% sodium chloride solution (150 mmol/l): saline; 10% of body weight] was markedly depressed. Urinary sodium excretion was 285 ± 62 vs 960 ± 58 μmol/min in the control period before CBDL (P < 0.001). This antinatriuresis was associated with a significant rise in plasma aldosterone concentration, from 52.5 ± 5.5 pg/ml before CBDL to 177 ± 50 pg/ml after CBDL (P < 0.02). Ascites was present in all salt-retaining CBDL dogs. 3. Bilateral adrenalectomy resulted in disappearance of ascites and in a rise in the natriuretic response to extracellular volume expansion. Urinary sodium excretion was 770 ± 124 μmol/min, a value significantly higher than in the CBDL dogs with intact adrenals (P < 0.001). Sodium balance studies in the adrenalectomized CBDL dogs during chronic deoxycorticosterone acetate (DOCA) treatment (25 mg/day) showed that in these animals there was failure to escape from the mineralocorticoid-induced sodium retention. Glomerular filtration rate and renal plasma flow did not change during the studies. 4. The present evidence supports the thesis that sodium retention in the CBDL dog results from a dual mechanism: (a) excess of circulating aldosterone and (b) an extra-adrenal factor which prevents escape from the salt-retaining effect of mineralocorticoids, in the CBDL dogs, thereby perpetuating the antinatriuresis in these animals.

Serial natriuretic response to atrial peptide in preascitic bile duct ligated dogs

1990 ◽  
Vol 68 (11) ◽  
pp. 1396-1400 ◽  
Author(s):  
Elizabeth Maher ◽  
Peter Cernacek ◽  
Mortimer Levy
Keyword(s):  
Bile Duct ◽  
Sodium Excretion ◽  
Bile Duct Ligation ◽  
Control Period ◽  
Sodium Balance ◽  
Sodium Retention ◽  
Time Intervals ◽  
Similar Time ◽  
Duct Ligation ◽  
Time Periods

We determined if nine precirrhotic unanaesthetized dogs with chronic bile duct ligation (CBDL) responded uniformly to atrial natriuretic peptide (ANF) by infusing this peptide sequentially over 8–12 weeks at 175 ng∙kg−1∙min−1 and observing the natriuretic response. ANF was administered every 2 weeks post-CBDL until the 8th week and given again during the cirrhotic phase with ascites present (10–12 weeks post-CBDL). Sodium balance studies were conducted at similar time intervals. During the control period and at weeks, 2, 6, and 8 post-CBDL all dogs responded to ANF with a significant change in sodium excretion (ΔUNaV, 50–240 μequiv./min). At these times, all dogs were in sodium balance. At week 4 and during the ascitic period, heterogeneity of response to ANF was observed. In the former interval, five dogs responded (ΔUNaV, 75–230 μequiv./min) and four did not, while in the latter interval, five dogs responded (ΔUNaV, 50–240 μequiv./min) and three did not (one dog died). In both time periods, there was severe urinary sodium retention (daily UNaV, 11 ± 3 and 2 ± 1 mequiv./day, respectively) while the dogs were ingesting 45 mequiv. Na+/day. The heterogeneity of natriuretic response was not correlated to plasma immunoreactive ANF, renin, or aldosterone levels. Plasma volume was significantly expanded from control during both intervals. We conclude that there is transient sodium retention during the 4th week post-CBDL, and that this period is associated with the heterogeneity of natriuretic response to ANF, despite the absence of ascites or edema.Key words: sodium excretion, cirrhosis, edema.

Effects of hypoproteinemia on renal hemodynamics, arterial pressure, and fluid volume

1987 ◽  
Vol 252 (1) ◽  
pp. F91-F98
Author(s):  
R. D. Manning
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Sodium Excretion ◽  
Sodium Intake ◽  
Renal Plasma Flow ◽  
Urinary Sodium Excretion ◽  
Renal Hemodynamics ◽  
Fluid Volume ◽  
Urinary Sodium ◽  
Plasma Aldosterone Concentration

The effects of long-term hypoproteinemia on renal hemodynamics, arterial pressure, and fluid volume were studied in eight conscious dogs over a 34-day period. Plasma protein concentration (PPC) was decreased by daily plasmapheresis, and the effects of decreasing and increasing sodium intake were measured. By the 12th day of plasmapheresis, during which sodium intake was 30 meq/day, PPC had decreased to 2.5 g/dl from a control value of 7.2 g/dl, mean arterial pressure had decreased to 78% of control, glomerular filtration rate (GFR) was 75.2% of control, and urinary sodium excretion was decreased. By day 18 of plasmapheresis, estimated renal plasma flow (ERPF) was decreased to 60% of control due to the decreased arterial pressure and an increase in renal vascular resistance. Also, plasma renin activity and plasma aldosterone concentration were both increased, and the relationship between mean arterial pressure and urinary sodium excretion was distinctly shifted to the left along the arterial pressure axis. In contradistinction to acute experiments, chronic hypoproteinemia results in decreases in GFR, ERPF, and urinary sodium excretion and has marked effects on both fluid volume and arterial pressure regulation.

Collecting Duct Na+/K+-ATPase Activity Is Correlated with Urinary Sodium Excretion in Rat Nephrotic Syndromes

2000 ◽  
Vol 11 (4) ◽  
pp. 604-615 ◽  
Author(s):  
GEORGES DESCHÊNES ◽  
ALAIN DOUCET
Keyword(s):  
Nephrotic Syndrome ◽  
Atpase Activity ◽  
Sodium Excretion ◽  
Collecting Duct ◽  
Urinary Sodium ◽  
Sodium Balance ◽  
Brattleboro Rats ◽  
Sodium Retention ◽  
Puromycin Aminonucleoside ◽  
Stimulation Of

Abstract. In puromycin aminonucleoside (PAN)-treated nephrotic rats, sodium retention is associated with increased Na+/K+-ATPase activity in the cortical collecting ducts (CCD). This study was undertaken to determine whether stimulation of Na+/K+-ATPase in the CCD is a feature of other experimental nephrotic syndromes, whether it might be responsible for renal sodium retention, and whether it is mediated by increased plasma vasopressin levels or activation of calcineurin. For this purpose, the time courses of urinary excretion of sodium and protein, sodium balance, ascites, and Na+/K+-ATPase activities in microdissected CCD were studied in rats with PAN or adriamycin nephrosis or HgCl2nephropathy. The role of vasopressin and calcineurin in PAN nephrosis were evaluated by measuring these parameters in Brattleboro rats and in rats treated with cyclosporin or tacrolimus. Despite different patterns of changes in urinary sodium and protein excretion in the three nephrotic syndrome models, there was a linear relationship between CCD Na+/K+-ATPase activities and sodium excretion in all three cases. The results also indicated that there was no correlation between proteinuria and sodium retention, but ascites was present only when proteinuria was associated with marked reduction of sodium excretion. Finally, the lack of vasopressin in Brattleboro rats or the inhibition of calcineurin by administration of either cyclosporin or tacrolimus did not prevent development of the nephrotic syndrome in PAN-treated rats or stimulation of CCD Na+/K+-ATPase. It is concluded that stimulation of Na+/K+-ATPase in the CCD of nephrotic rats might be responsible for sodium retention and that this phenomenon is independent of proteinuria and vasopressin and calcineurin activities.

Influence of captopril on fluid and electrolyte balances and adrenocortical responses during sodium deprivation in the rat

1983 ◽  
Vol 98 (2) ◽  
pp. 211-NP ◽  
Author(s):  
Annette McKeever ◽  
J. A. Oliver ◽  
I. W. Henderson ◽  
Warwick Mosley
Keyword(s):  
Sodium Excretion ◽  
Enzyme Inhibitor ◽  
Gastric Lavage ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Zona Glomerulosa ◽  
Urinary Sodium ◽  
Sodium Balance ◽  
Deficient Diet ◽  
Angiotensin I Converting Enzyme

An angiotensin I-converting enzyme inhibitor (captopril) was given by gastric lavage at a dose of 30 mg/kg body weight per day to Long–Evans rats for a 13-day period during which they received a sodium-deficient diet. This regime was preceded by a 3-day period during which measurements were made on the animals on a sodium-replete dietary intake. Control sodium-deprived rats showed increased plasma renin activities, increased peripheral aldosterone concentrations and reduced urinary sodium excretion; they maintained positive sodium balance and the zona glomerulosa of the adrenal cortex hypertrophied. Captopril-treated sodium-deprived rats failed to reduce urinary sodium excretion sufficiently and entered a period of marked and sustained negative sodium balance. Peripheral aldosterone concentrations after 12 days of sodium deprivation in the presence of captopril treatment were similar to those of sodium-replete rats. The adrenocortical zona glomerulosa of the captopril-treated rats did not increase in size and regressive changes were noted.

The control of sodium excretion

1978 ◽  
Vol 235 (3) ◽  
pp. F163-F173 ◽  
Author(s):  
H. E. de Wardener
Keyword(s):  
Proximal Tubule ◽  
Sodium Excretion ◽  
Collecting Duct ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Sodium Balance ◽  
Sodium Reabsorption ◽  
Loop Of Henle ◽  
Salt Loading ◽  
Large Fluctuations

The kidneys of a normal man filter approximately 24,000 meq sodium/day, reabsorb about 23,900, and yet can make a 1--2 meq change in 24-h urinary sodium excretion. The control of urinary sodium excretion, therefore, depends, first, on ensuring that the bulk of the sodium is reabsorbed, a function which is carried out in the proximal tubule and ascending loop of Henle. Second, it depends on adjusting the reabsorption of the small quantity of sodium which is delivered into the collecting duct so that the amount excreted in the urine is that required to maintain sodium balance. The bulk reabsorptive mechanisms can be considered as buffers to prevent large fluctuations in the amount of sodium delivered to the collecting duct, thus facilitating the fine adjustments of reabsorption which are made at this site. In conditions other than extreme salt loading or deprivation, changes in sodium reabsorption in the proximal tubule and loop of Henle probably have little, if any, effect on urinary sodium excretion. Sodium reabsorption in the proximal tubule and the collecting duct appears to be influenced by unidentified circulating substances.

Neurohumoral modulators and sodium balance in experimental heart failure

1993 ◽  
Vol 264 (4) ◽  
pp. H1187-H1193 ◽  
Author(s):  
D. Villarreal ◽  
R. H. Freeman ◽  
R. A. Johnson
Keyword(s):  
Heart Failure ◽  
Sodium Excretion ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Sodium Balance ◽  
Renal Nerves ◽  
Av Fistula ◽  
Before And After ◽  
High Output Heart Failure

The acute and chronic interactions of the renal nerves, atrial natriuretic factor (ANF), and mineralocorticoids for the regulation of sodium balance were examined in dogs with an arteriovenous (AV) fistula and the syndrome of high-output heart failure (HOHF) (n = 6). After the AV fistula and bilateral renal denervation, the animals avidly retained sodium for 5-7 days and then regained sodium balance for the subsequent 3 wk. This compensation was associated with the sustained elevations of plasma ANF and the normalization of plasma renin. Subsequent administration of deoxycorticosterone acetate (DOCA) for 10 days produced consistent sodium retention despite additional elevations in plasma ANF. All of these responses were similar to previous studies in AV fistula dogs with intact renal nerves. In a separate part of the study, the renal actions of acute synthetic ANF infusions were examined in these renal-denervated AV fistula dogs before and after DOCA. In the pre-DOCA experiments, ANF infusions at 15, 30, and 100 ng.kg-1.min-1 produced dose-related increases in urinary sodium excretion and significant elevations in creatinine clearance. In the presence of DOCA, urinary sodium excretion was markedly attenuated during identical ANF infusions. The composite results suggest that mineralocorticoids have an important modulatory role for the regulation of sodium balance in experimental HOHF. However, compared with earlier studies in compensated AV fistula dogs with intact renal nerves, the present studies demonstrate that blockade of efferent renal sympathetic nerve activity can restore the natriuretic expression of acute elevations in circulating ANF.

Effects of chronic L-NAME on nitrotyrosine expression and renal vascular reactivity in rats with chronic bile-duct ligation

2008 ◽  
Vol 115 (2) ◽  
pp. 57-68 ◽  
Author(s):  
Antonia Alcaraz ◽  
David Hernández ◽  
David Iyú ◽  
Rubén Mota ◽  
Noemí M. Atucha ◽  
...  
Keyword(s):  
Bile Duct ◽  
Vascular Reactivity ◽  
Bile Duct Ligation ◽  
Sodium Balance ◽  
Biliary Cirrhosis ◽  
Sodium Retention ◽  
Vascular Response ◽  
Experimental Cirrhosis ◽  
Duct Ligation ◽  
Renal Vascular

In liver cirrhosis, elevated levels of NO and ROS (reactive oxygen species) might greatly favour the generation of peroxynitrite. Peroxynitrite is a highly reactive oxidant and it can potentially alter the vascular reactivity and the function of different organs. In the present study, we evaluated whether peroxynitrite levels are related to the progression of renal vascular and excretory dysfunction during experimental cirrhosis induced by chronic BDL (bile-duct ligation) in rats. Experiments were performed at 7, 15 and 21 days after BDL in rats and in rats 21 days post-BDL chronically treated with L-NAME (NG-nitro-L-arginine methyl ester). Sodium balance, BP (blood pressure), basal RPP (renal perfusion pressure) and the renal vascular response to PHE (phenylephrine) and ACh (acetylcholine) in isolated perfused kidneys were measured. NO levels were calculated as 24-h urinary excretion of nitrites, ROS as TBARS (thiobarbituric acid-reacting substances), and peroxynitrite formation as the renal expression of nitrotyrosine. BDL rats had progressive sodium retention, and decreased BP, RPP and renal vascular responses to PHE and ACh in the time following BDL. They also had increasing levels of NO and ROS, and renal nitrotyrosine accumulation, especially in the medulla. All of these changes were either prevented or significantly decreased by chronic L-NAME administration. In conclusion, these results suggest that the increasing levels of peroxynitrite might contribute to the altered renal vascular response and sodium retention in the development of the experimental biliary cirrhosis. Moreover, the beneficial effects of decreasing NO synthesis are, at least in part, mediated by anti-peroxinitrite-related effects.

Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

2004 ◽  
Vol 286 (2) ◽  
pp. F288-F297 ◽  
Author(s):  
Martin Græbe ◽  
Lone Brønd ◽  
Sten Christensen ◽  
Søren Nielsen ◽  
Niels V. Olsen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Urinary Sodium Excretion ◽  
Proximal Tubules ◽  
Sodium Balance ◽  
Sodium Reabsorption ◽  
Sodium Retention ◽  
Common Bile Duct Ligation ◽  
Protein Levels ◽  
Duct Ligation ◽  
Synthase Inhibitor

The present study investigated sodium balance and renal tubular function in cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were treated with the nonselective NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) starting on the day of common bile duct ligation (CBL). Three weeks of daily sodium balance studies showed that CBL rats developed sodium retention compared with sham-operated rats and that l-NAME treatment dose dependently deteriorated cumulative sodium balance by reducing urinary sodium excretion. Five weeks after CBL, renal clearance studies were performed, followed by Western blotting of the electroneutral type 3 sodium/proton exchanger (NHE3) and the Na-K-ATPase present in proximal tubules. Untreated CBL rats showed a decreased proximal reabsorption with a concomitant reduction of NHE3 and Na-K-ATPase levels, indicating that tubular segments distal to the proximal tubules were responsible for the increased sodium reabsorption. l-NAME-treated CBL rats showed an increased proximal reabsorption measured by the lithium clearance method and showed a marked increase in NHE3 and Na-K-ATPase protein levels. Our results show that chronic l-NAME treatment exacerbates the sodium retention found in CBL rats by a significant increase in proximal tubular reabsorption.

Epithelial sodium channel (ENaC) subunit mRNA and protein expression in rats with puromycin aminonucleoside-induced nephrotic syndrome

2003 ◽  
Vol 104 (4) ◽  
pp. 389-395 ◽  
Author(s):  
A. AUDIGÉ ◽  
Z.R. YU ◽  
B.M. FREY ◽  
D.E. UEHLINGER ◽  
F.J. FREY ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Sodium Channel ◽  
Mrna Expression ◽  
Sodium Excretion ◽  
Early Phase ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Sodium Retention ◽  
Puromycin Aminonucleoside ◽  
Epithelial Sodium Channel Enac

In experimental nephrotic syndrome, urinary sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt retention has not been completely elucidated. The rate-limiting constituent of collecting duct sodium transport is the epithelial sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague–Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of αENaC, βENaC and γENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of αENaC and βENaC mRNA abundance on days 1 and 2 preceded sodium retention on days 2 and 3. Conversely, down-regulation of αENaC, βENaC and γENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of sodium excretion to control values. The amounts of αENaC, βENaC and γENaC proteins were not increased during PAN-induced sodium retention. In conclusion, ENaC mRNA expression, especially αENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.

Evidence that intrarenal bradykinin plays a role in regulation of renal function

1993 ◽  
Vol 265 (4) ◽  
pp. E648-E654 ◽  
Author(s):  
H. M. Siragy
Keyword(s):  
Renal Function ◽  
Sodium Excretion ◽  
Sodium Intake ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Sodium Balance ◽  
Kinin System ◽  
Plasma Aldosterone Concentration ◽  
Low Sodium

Bradykinin (BK) is produced by the kidney, but the role of the renal kallikrein-kinin system (KKS) in the control of renal function is not understood. We studied the effects of intrarenal infusion of the BK antagonist, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg-trifluoroacetic acid (BKA, n = 5) and BK (n = 4) alone or combined with antagonist (BKA 0.025 ng.kg-1 x min-1 + BK 0.25 ng.kg-1 x min-1, n = 4) in uninephrectomized conscious dogs in sodium balance at 10 and 80 meq/day. During low sodium intake, administration of BKA (infusions from 0.025 to 2.5 ng.kg-1 x min-1) caused a significant antidiuresis (P < 0.0001) and antinatriuresis (P < 0.0001) and a decrease in fractional sodium excretion (P < 0.0001). There were no changes in estimated renal plasma flow (RPF) or glomerular filtration rate during intrarenal administration of BKA at 0.025 and 0.25 ng.kg-1 x min-1. A dose of 2.5 ng.kg-1 x min-1 BKA caused a significant decrease in RPF. There were no changes in plasma aldosterone concentration, plasma renin activity, or systemic arterial pressure during intrarenal BKA administration. At 80 meq/day sodium balance (n = 5), intrarenal administration of BKA did not cause any systemic or renal effects. Intrarenal administration of BK at 0.25 ng.kg-1 x min-1 during low sodium balance caused an increase in urine flow rate and urinary sodium excretion. Coinfusion of BK with BKA completely abrogated the renal excretory changes induced by BKA. These data suggest that intrarenal KKS plays a role in control of renal function largely by a tubular mechanism during low sodium intake.

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