Bile Salts, Hypotension and Obstructive Jaundice (original) (raw)
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Mechanism of bile salt vasoactivity: dependence on calcium channels in vascular smooth muscle
British Journal of Pharmacology, 1994
The vasoactive mechanisms of bile salts have been investigated in rat isolated portal venous and superior mesenteric arterial rings and perfused mesentery. The isolated perfused mesentery was precontracted with a selective α1‐adrenoceptor agonist, cirazoline. Incremental doses of tauroursodeoxycholate (TUDC), taurochenodeoxycholate (TCDC) and taurodeoxycholate (TDC) caused a dose‐dependent vasorelaxation. The order of potency of the vasodilator effect was TDC > TCDC > TUDC. The effect of TDC (1.9 × 10−8 −1.9 × 10−6 mol) was examined before and after propranolol (3 μm), tetraethylammonium (5 mM), ouabain (10−5 M), NG‐nitro‐l‐arginine methyl ester (10−4 M) and capsaicin (50 mg kg−1) to block, respectively, β‐adrenoceptors, K+‐channels, Na+, K+‐ATPase, nitric oxide synthase, and primary sensory nerves. The vasodilator effect of TDC was not affected by any of these blocking agents or by denuding vascular endothelium with distilled water. Infusion of TDC (1.9 × 10−8 −1.9 × 10−6 mol...
Haemodynamic and renal evolution of the bile duct-ligated rat
Clinical Science, 2000
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, 111.5p4.7 mmHg ; sham-operated, 122.9p3.0 mmHg) and peripheral vascular resistance (BDL, 2.63p0.08 units ; sham-operated, 2.93p0.09 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, 58.8p3.9 ml:min − 1 :100 g − 1 ; sham-operated, 43.9p1.5 ml:min − 1 :100 g − 1) and stroke volume (BDL, 147.2p12.7 ml:beat − 1 :100 g − 1 ; sham-operated, 109.0p4.2 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, 2.2p0.2 mmol/100 g ; sham-operated, 1.5p0.2 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.
Vascular reactivity in reversible experimental obstructive jaundice
Journal of Surgical Research, 1987
We studied the effect of jaundice on in vitro vascular reactivity to cumulative doses of norepinephrine (NE) by measuring the maximal response (Rmax) and the concentration of NE required to cause a 50% response (ED50) of isolated vascular smooth muscle. For this we prepared helically cut strips of thoracic aorta from bile duct ligated (BDL) rats at 1, 3, 6, 14, and 28 days postligation and compared them with those of nonoperated and sham-operated controls. From 1 to 6 days post-BDL, changes in liver blood chemistry and liver histology indicated cholestasis with necrosis. By 14 days, the tests for liver function and histology indicated a return to normal liver function and histology. In nonoperated controls, mean Rmax increased significantly from 883 +/- 67 mg of tension to 1220 +/- 68 mg of tension (P less than 0.0025) from 0 to 28 days, whereas ED50 remained unchanged. In sham-operated controls and BDL rats, an age-dependent increase in Rmax was also observed. However, in the sham groups, ED50 tended to decrease compared with nonoperated controls, indicating a surgically induced "sensitization" phenomenon of the vascular smooth muscle. In contrast, this was not seen in BDL rats since in these groups, the ED50 remained unchanged and significantly higher than in the sham groups, in both the jaundiced (1-6 days) and nonjaundiced (14-28 days) period. Furthermore, these changes occurred in the absence of any alteration in portal pressure. These changes may be important in understanding the mechanism of hypotension and shock in postoperative patients with obstructive jaundice even after the jaundice has been relieved.
Bile salt-associated electrolyte secretion
Experimental and Toxicologic Pathology, 1992
The mechanisms involved in bile salt-induced choleresis are poorly known. To give an insight in this physiological process, bile salt-associated electrolyte secretion was studied following relief of a short-term (2 h) biliary .obstruction in the rat, an experimental model that shows an important diminution of bile salt choleretic efficiency. For this purpose, biliary excretion of total bile salts and electrolytes (sodium, chloride and bicarbonate) were studied in such a model during taurocholate infusion at increasing rates. The results showed that bile flow, bile salt output and electrolyte secretion stimulated by taurocholate,administration were decreased in the rats that were subjected to biliary obstruction. Besides, the choleretic efficiency of the excreted bile salts, as estimated by the slope of the regression line of bile flow vs. bile salt output, was diminished by 46 % (p < 0.005). Multiple regression analysis of bile flow vs. bile salt and electrolyte outputs allowed to detect a selective diminution of the fraction of bile flow related to bile salt-associated electrolyte secretion ("secretory fraction" of the choleretic efficiency of bile salts) (3.2 ± 0.3 vs. 2.5 ± 0.2L1mol, p < 0.05) whereas the "osmotic fraction" of the choleretic efficiency of bile salts was not modified by the treatment (5. a ± 0.4 vs. 5.1 ± 0.3 Llmol, p> 0.05). Since both chloride and bicarbonate biliary concentrations in the volume of bile stimulated by taurocholate were reduced by 53 % and 52 % respectively, a role of these anions in the generation of bile salt-induced choleresis was suggested. Possible mechanisms involved in such a process and in its early impairment during cholestasis are discussed.
British Journal of Surgery, 1997
Systemic hypotension may result in postoperative renal failure in jaundiced patients. Attenuated responsiveness to catecholamines and hypovolaemia has been reported in jaundiced animals and may be a mechanism contributing to the increased susceptibility of jaundiced patients to haemorrhagic shock. This suggests that an alternative to vasoactive amines to control perioperative hypotension could be desirable. This study evaluated the pressor response to vasopressin in normovolaemic 3-day bile duct-ligated rats and in 3-day bile duct-ligated rats after an acute controlled haemorrhage. It also evaluated the response after volume loading with 0.9 per cent saline, 7.5 per cent saline, colloid and mannitol before controlled haemorrhage. In addition, blood volume was measured using radiolabelled albumin. All the data obtained from bile duct-ligated rats were compared with data from sham-operated animals. Attenuated pressor responses to vasopressin were not observed in either normotensive bile duct-ligated rats or in the bile duct-ligated rats subjected to controlled haemorrhage. Volume loading with the four fluids over the dosing range 2.5-7.5 microliters per g body-weight in bile duct-ligated rats reversed the susceptibility to haemorrhagic hypotension. Although no reduction in blood volume was demonstrated, bile duct-ligated rats may have a reduced effective blood volume manifesting itself as a latent hypovolaemia and/or tendency to hypotension. Preoperative fluid loading could be beneficial because it corrects hypovolaemia and improves cardiovascular function, as well as improving the cardiovascular response to haemorrhage.
Adaptive hepatic changes in mild stenosis of the common bile duct in the rat
Research in Experimental Medicine, 1998
Adaptive hepatic changes were investigated in rats with mild stenosis of the common bile duct and in sham-operated controls. The studies were performed 24 h and 7-12 days postoperatively. A continuous intravenous infusion of taurocholic acid at stepwise-increasing rates was performed to explore the responses to bile acid effects. During the infusion, bile flow and the outputs of bile acids, phospholipids, cholesterol, alkaline phosphatase and gamma glutamyl transpeptidase were studied. At the end of the infusion, hepatic morphometric measurements were performed. In other experimental sets, biliary excretions of horseradish peroxidase, a marker of microtubule-dependent vesicular transport in the hepatocyte, and sulphobromophthalein, a wellknown organic anion model, were studied. In other rats, bile acid pool size and composition were determined by depletion of bile. The results in rats with mild stenosis maintained for 24 h showed a greater susceptibility to the toxicity of taurocholic acid, as revealed by the abrupt decrement in bile flow at high rates of infusion, and increased outputs of phospholipids and canalicular enzymes. Conversely, rats with mild stenosis maintained for 7-12 days showed decreased bile acid maximum secretory rate and biliary outputs of phospholipids and canalicular enzymes, as well as hepatocyte hypertrophy. These findings may explain the limited hepatic and systemic repercussion of experimental mild stenosis of the common bile duct and help us to understand the early stages of constriction of the common bile duct in man.
Intrarenal mechanisms of salt retention after bile duct ligation in rats
Journal of Clinical Investigation, 1976
order to study renal salt-retaining mechanisms during the early stages of ascites formation, rats were subjected to bile duct ligation. After this procedure, plasma volumes were found to be reduced and hematocrits slightly increased. The whole-kidney glomerular filtration rate and plasma flows were reduced to 59 and 57% of control values, but the filtration fraction was unchanged. Absolute sodium excretion, as well as the fraction of the filtered sodium load excreted, was also significantly reduced. When micropuncture techniques were used to examine the function of single superficial nephrons, the glomerular filtration rate in these nephrons was found to be reduced to 70% of controlled values, and fractional reabsorption was found to be increased at all accessible sites along the nephron. Filtration by intermediate and juxtamedullary nephrons, determined by Hanssen's technique, was reduced to 55 and 48% of control values. By the use of radioactive microspheres, it was demonstrated that blood flow to superficial, intermediate, and juxtamedullary nephrons was reduced to 49, 59, and 73% of control values. Filtration by superficial nephrons decreased much more than plasma flow-a finding which suggests that the measured increase in fractional reabsorption was associated with an increase in the superficial nephron filtration fraction. From this study, it appears that two factors play an important part in the sodium retention observed in the initial stages of ascites formation following bile duct ligation in rats: (a) a decrease in the filtered sodium