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.

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.

Haemodynamic and renal evolution of the bile duct-ligated rat

2000 ◽  
Vol 98 (5) ◽  
pp. 611-617 ◽  
Author(s):  
Concepción MARTÍNEZ-PRIETO ◽  
M. Clara ORTÍZ ◽  
Lourdes A. FORTEPIANI ◽  
Jose Antonio RUIZ-MACIÁ ◽  
Noemí M. ATUCHA ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Bile Duct ◽  
Rat Model ◽  
Bile Duct Ligation ◽  
Plasma Renin ◽  
Sodium Balance ◽  
Sodium Retention ◽  
Peripheral Vasodilation ◽  
Duct Ligation ◽  
Conscious Animals

In the present study we have characterized the evolution of changes in systemic haemodynamics (thermodilution in conscious animals) and sodium balance (metabolic cages) in a model of liver cirrhosis induced by chronic bile duct ligation (BDL). Mean arterial pressure (BDL, 111.5±4.7 mmHg; sham-operated, 122.9±3.0 mmHg) and peripheral vascular resistance (BDL, 2.63±0.08 units; sham-operated, 2.93±0.09 units) were lower in BDL rats from day 12 after surgery and decreased progressively throughout the following days. Portal hypertension was evident earlier in BDL rats and was maintained throughout the study period. Cardiac index (BDL, 58.8±3.9 ml·min-1·100 g-1; sham-operated, 43.9±1.5 ml·min-1·100 g-1) and stroke volume (BDL, 147.2±12.7 ml·beat-1·100 g-1; sham-operated, 109.0±4.2 ml·beat-1·100 g-1) were significantly elevated in the BDL rats only from day 18 after surgery. There were no significant differences in sodium balance between the groups until day 16 after surgery, at which time BDL animals started to retain significantly more sodium than the controls. Sodium retention increased progressively, and at day 20 BDL rats had retained 0.7 mmol/100 g more than the control animals (accumulated retention: BDL, 2.2±0.2 mmol/100 g; sham-operated, 1.5±0.2 mmol/100 g). Plasma renin activity and aldosterone concentration were not elevated in the BDL animals at days 12, 16 or 20 after surgery. These data indicate that the BDL rat model shows early portal hypertension, peripheral vasodilation and arterial hypotension, several days before sodium retention is detectable, and in the absence of changes in plasma levels of renin and aldosterone. Overall, these data suggest that, in the BDL rat model, sodium retention is secondary to portal hypertension and peripheral vasodilation.

scholarly journals CIRRHOSIS INDUCES APOPTOSIS IN RENAL TISSUE THROUGH INTRACELLULAR OXIDATIVE STRESS

2015 ◽  
Vol 52 (1) ◽  
pp. 65-71 ◽  
Author(s):  
Keli Cristina Simões da SILVEIRA ◽  
Cassiana Macagnan VIAU ◽  
Josiane Raskopf COLARES ◽  
Jenifer SAFFI ◽  
Norma Possa MARRONI ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Membrane Potential ◽  
Bile Duct ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Bile Duct Ligation ◽  
Decompensated Cirrhosis ◽  
Biliary Cirrhosis ◽  
Duct Ligation

Background Renal failure is a frequent and serious complication in patients with decompensated cirrhosis. Objectives We aimed to evaluate the renal oxidative stress, cell damage and impaired cell function in animal model of cirrhosis. Methods Secondary biliary cirrhosis was induced in rats by ligation of the common bile duct. We measured TBARS, ROS and mitochondrial membrane potential in kidney as markers of oxidative stress, and activities of the antioxidant enzymes. Relative cell viability was determined by trypan blue dye-exclusion assay. Annexin V-PE was used with a vital dye, 7-AAD, to distinguish apoptotic from necrotic cells and comet assay was used for determined DNA integrity in single cells. Results In bile duct ligation animals there was significant increase in the kidney lipoperoxidation and an increase of the level of intracellular ROS. There was too an increase in the activity of all antioxidant enzymes evaluated in the kidney. The percentage viability was above 90% in the control group and in bile duct ligation was 64.66% and the dominant cell death type was apoptosis. DNA damage was observed in the bile duct ligation. There was a decreased in the mitochondrial membrane potential from 71.40% ± 6.35% to 34.48% ± 11.40% in bile duct ligation. Conclusions These results indicate that intracellular increase of ROS cause damage in the DNA and apoptosis getting worse the renal function in cirrhosis.

Peripheral vascular neuroeffector mechanisms in experimental cholestasis

1993 ◽  
Vol 265 (3) ◽  
pp. G579-G586 ◽  
Author(s):  
G. Jacob ◽  
O. Said ◽  
J. Finberg ◽  
A. Bomzon
Keyword(s):  
Electrical Stimulation ◽  
Bile Duct ◽  
Vascular Reactivity ◽  
Bile Duct Ligation ◽  
Norepinephrine Uptake ◽  
Pithed Rats ◽  
Duct Ligation ◽  
Adrenoceptor Agonists

Jaundiced patients have systemic hypotension and are more susceptible to hemorrhagic shock than nonjaundiced individuals. We have hypothesized that the mechanism whereby these cardiovascular complications arise is linked to a disturbance of the vascular neuroeffector process in the cardiovascular system. With the use of 3-day bile duct-manipulated (sham-operated) and bile duct-ligated rats, we have evaluated alpha-adrenoceptor function and amine uptake using in vivo and in vitro techniques. Blunted pressor responsiveness to norepinephrine, electrical stimulation, and the alpha 1-adrenoceptor agonists, methoxamine and phenylephrine, was observed in the bile duct-ligated pithed rats. In contrast, normal responsiveness to BHT-933 and clonidine, the alpha 2-adrenoceptor agonists, was seen in these animals. The uptake 1 blocker, cocaine, caused potentiation of equal magnitudes of the pressor responsiveness to electrical stimulation and norepinephrine in the sham-operated and bile duct-ligated pithed rats. In aortic rings prepared from the bile duct-ligated rats, blunted in vitro vascular reactivity to norepinephrine and the same alpha 1-adrenoceptor agonists was seen. Bile duct ligation had no effect on norepinephrine uptake or its kinetics in stressed and unstressed arterial rings and portal veins. We have thus concluded that bile duct ligation induces a defect in the functional expression of cardiovascular alpha 1-adrenoceptors without any effects on the activity of alpha 2-adrenoceptors or norepinephrine uptake.

Differential alteration of cytochrome P450 isoenzymes in two experimental models of cirrhosis

2000 ◽  
Vol 78 (11) ◽  
pp. 912-919 ◽  
Author(s):  
Marie-Claude Bastien ◽  
François Leblond ◽  
Vincent Pichette ◽  
Jean-Pierre Villeneuve
Keyword(s):  
Cytochrome P450 ◽  
Carbon Tetrachloride ◽  
Bile Duct ◽  
Serum Albumin ◽  
Breath Test ◽  
Bile Duct Ligation ◽  
Biliary Cirrhosis ◽  
Breath Tests ◽  
Duct Ligation

Liver diseases are associated with a decrease in hepatic drug elimination, but there is evidence that cirrhosis does not result in uniform changes of cytochrome P450 (CYP) isoenzymes. The objective of this study was to determine the content and activity of four CYP isoenzymes in the bile duct ligation and carbon tetrachloride (CCl4)-induced models of cirrhosis. The hepatic content of CYP1A, CYP2C, CYP2E1, and CYP3A was measured by Western blot analysis. CYP activity in vivo was evaluated with breath tests using substrates specific for different isoenzymes: caffeine (CYP1A2), aminopyrine (CYP2C11), nitrosodimethylamine (CYP2E1), and erythromycin (CYP3A). Bile duct ligation resulted in biliary cirrhosis; CYP1A, CYP2C and CYP3A content was decreased and the caffeine, aminopyrine, and erythromycin breath tests were reduced whereas CYP2E1 content and the nitrosodimethylamine breath test were unchanged compared with controls. CCl4 treatment resulted in cirrhosis of varying severity as assessed from the decrease in liver weight and serum albumin. In rats with mild cirrhosis, CYP content was comparable with controls except for a decrease in CYP2C. The activity of CYPs was also unchanged except for an increase in CYP2E1 activity. In rats with more severe cirrhosis, the content of all four CYP isoenzymes and the caffeine, aminopyrine, and erythromycin breath tests were reduced whereas the nitrosodimethylamine breath test was unchanged. In both models of cirrhosis, there was a significant correlation between the breath tests results and the severity of cirrhosis as assessed from serum albumin levels. These results indicate that content and the catalytic activity of individual CYP enzymes are differentially altered by cirrhosis in the rat and also suggest that drug probes could be useful to assess hepatic functional reserve.Key words: breath test, cirrhosis, cytochrome P450, bile duct ligation, carbon tetrachloride.

Glutathione status in liver and plasma during development of biliary cirrhosis after bile duct ligation

1998 ◽  
Vol 198 (4) ◽  
pp. 167-174 ◽  
Author(s):  
Edmund Purucker ◽  
Ron Winograd ◽  
Elke Roeb ◽  
Siegfried Matern
Keyword(s):  
Bile Duct ◽  
Bile Duct Ligation ◽  
Biliary Cirrhosis ◽  
Glutathione Status ◽  
Duct Ligation

scholarly journals Antioxidant and anti-inflammatory action of melatonin in an experimental model of secondary biliary cirrhosis induced by bile duct ligation

2016 ◽  
Vol 22 (40) ◽  
pp. 8918 ◽  
Author(s):  
Josieli Raskopf Colares ◽  
Elizângela Gonçalves Schemitt ◽  
Renata Minuzzo Hartmann ◽  
Francielli Licks ◽  
Mariana do Couto Soares ◽  
...  
Keyword(s):  
Bile Duct ◽  
Experimental Model ◽  
Bile Duct Ligation ◽  
Biliary Cirrhosis ◽  
Duct Ligation ◽  
Anti Inflammatory ◽  
Secondary Biliary Cirrhosis ◽  
Inflammatory Action

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.

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