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Biomedical subjects

R Moreau

Publications and source records attributed to R Moreau.

At least 91 records · Page 5Linked to original sources
PubMed1997

Plasma concentrations of cyclic 3', 5'-guanosine monophosphate in patients with cirrhosis: relationship with atrial natriuretic peptide and haemodynamics.

Little is known about the plasma concentrations of cyclic 3',5'-guanosine monophosphate (cGMP) in patients with cirrhosis. However, plasma cGMP concentrations provide information on cellular cGMP production by particulate guanylyl cyclases (which are stimulated by natriuretic peptides, such as atrial natriuretic peptide; ANP). In contrast, because intracellular cGMP elicits vasorelaxant mechanisms, plasma cGMP concentrations may be related to haemodynamic alterations in patients with cirrhosis. The aim of the present study was to measure plasma cGMP concentrations in patients with cirrhosis and controls and to examine the relationship between cGMP levels and plasma ANP concentrations and haemodynamic values. Plasma concentrations of cGMP and ANP and splanchnic and systemic haemodynamics were measured in 23 subjects; 13 subjects had cirrhosis and 10 were controls. All subjects had normal glomerular filtration. Plasma cGMP concentrations were significantly higher in patients (6.5 +/- 0.8 pmol/mL) than in controls (2.7 +/- 0.4 pmol/mL), while plasma ANP concentrations did not significantly differ between the two groups (127 +/- 22 and 123 +/- 27 pg/mL, respectively). In patients with cirrhosis, no significant correlation was found between plasma cGMP concentrations and plasma ANP concentrations, hepatic venous pressure gradient, cardiac output or systemic vascular resistance. In conclusion, in patients with cirrhosis, increased plasma cGMP concentrations may be due to an activation of particulate guanylyl cyclases by natriuretic peptides other than ANP. The present study suggest that plasma cGMP concentrations are not related to cirrhosis-induced haemodynamic alterations.

Adult↗
PubMed1997

Responsiveness to growth factors in aortic vascular smooth muscle cells from rats with cirrhosis.

Hemodynamic changes in cirrhosis may be associated with alterations in aortic vascular smooth muscle cell (AVSMC) function. The present study compared the proliferative response to serum and growth factors in cirrhotic and control AVSMC. Serum from cirrhotic rats, cirrhotic cell lysates, and the conditioned medium of cultured cirrhotic AVSMC induced an increase in [3H]thymidine incorporation in control but not in cirrhotic AVSMC. Platelet-derived growth factor-beta (PDGF-BB) induced a greater increase in [3H]thymidine incorporation in cirrhotic than in control cells. [3H]thymidine incorporation induced by cirrhotic conditioned medium was blocked by anti-PDGF antibody. Immunoblot studies showed that the anti-PDGF antibody recognized a 30-kDa protein in the conditioned medium of cirrhotic AVSMC culture, a protein corresponding to PDGF. Binding studies of PDGF-BB indicated a twofold increase in receptor density in cirrhotic AVSMC with no alteration in affinity for PDGF-BB. We conclude that an increased responsiveness of cirrhotic AVSMC to the PDGF could contribute to alterations in AVSMC and muscle cell tone that may play a role in the hemodynamic changes in cirrhosis.

Animals↗
PubMed1997

Pharmacological and biochemical evidence for the regulation of osteocalcin secretion by potassium channels in human osteoblast-like MG-63 cells.

Previous reports have suggested the involvement of voltage-activated calcium (Ca2+) channels in bone metabolism and in particular on the secretion of osteocalcin by osteoblast-like cells. We now report that potassium (K+) channels can also modulate the secretion of osteocalcin by MG-63 cells, a human osteosarcoma cell line. When 1,25-dihydroxyvitamin D3(1,25(OH)2D3)-treated MG-63 cells were depolarized by step increases of the extracellular K+ concentration ([K+]out) from 5-30 mM, osteocalcin (OC) secretion increased from a control value of 218 +/- 13 to 369 +/- 18 ng/mg of protein/48 h (p < 0.005 by analysis of variance). In contrast, in the absence of 1,25(OH)2D3, there is no osteocalcin secretion nor any effect of cell depolarization on this activity. The depolarization-induced increase in 1,25(OH)2D3-dependent osteocalcin secretion was totally inhibited in the presence of 10 microM Nitrendipine (a Ca2+ channel blocker, p < 0.005) without affecting cellular alkaline phosphatase nor cell growth. Charybdotoxin, a selective blocker of Ca2+-dependent K+ channels (maxi-K) present in MG-63 cells, stimulated 1,25(OH)2D3-induced osteocalcin synthesis about 2-fold (p < 0.005) after either 30, 60, or 120 minutes of treatment. However, Charybdotoxin was without effect on basal release of osteocalcin in the absence of 1,25(OH)2D3 pretreatment. Using patch clamp technique, we occasionally observed the presence of a small conductance K+ channel, compatible with an ATP-dependent K+ channel (GK[ATP]) in nonstimulated cells, whereas multiple channel openings were observed when cells were treated with Diazoxide, a sulfonamide derivative which opens GK(ATP). Western blot analysis revealed the presence of the N-terminal peptide of GK(ATP) in MG-63 cells, and its expression was regulated with the proliferation rate of these cells, maximal detection by Western blots being observed during the logarithmic phase of the cycle. Glipizide and Glybenclamide, selective sulfonylureas which can block GK(ATP), dose-dependently enhanced 1,25(OH)2D3-induced OC secretion (p < 0.005). Reducing the extracellular calcium concentration with EGTA (microM range) totally inhibited the effect of Glipizide and Glybenclamide on osteocalcin secretion (p < 0.005), which remained at the same levels as controls. Diazoxide totally prevented the effect of these sulfonylureas. These results suggest that voltage-activated Ca2+ channels triggered via cell depolarization can enhance 1,25(OH)2D3-induced OC release by MG-63 cells. In addition, OC secretion is increased by blocking two types of K+ channels: maxi-K channels, which normally hyperpolarize cells and close Ca2+ channels, and GK(ATP) channels. The role of these channels is closely linked to the extracellular Ca2+ concentration.

Adenosine Triphosphate↗
PubMed1997

Relationship between portal pressure, esophageal varices, and variceal bleeding on the basis of the stage and cause of cirrhosis.

BACKGROUND AND METHODS: Hepatic venous pressure gradient, esophageal varices, and variceal bleeding were investigated in 957 patients with cirrhosis. The causes (alcoholic/virus) and stage (Child-Pugh's classification) of cirrhosis were also taken into account. RESULTS: The prevalence of variceal bleeding was 35% in patients with large varices and 17% in those with small varices (P < 0.05). It was higher in patients with alcoholic cirrhosis (41% and 19%, respectively) than in those with viral cirrhosis (22% and 10%, respectively). In patients with alcoholic cirrhosis the hepatic venous pressure gradient was higher in Child A and B patients with small or large varices than in those with no varices; these differences were not found in Child C patients and in patients with viral cirrhosis. In all subgroups the pressure gradient was higher in Child C patients than in Child A patients. There was no significant difference in the hepatic venous pressure gradient between patients with varices and previous variceal bleeding and those with no bleeding whatever the stage of cirrhosis. CONCLUSIONS: This study shows that the hepatic venous pressure gradient is associated with the stage and causes of cirrhosis and the presence of varices. These factors should be taken into account in studies evaluating the hepatic venous pressure gradient in heterogeneous groups of patients.

Esophageal and Gastric Varices↗
PubMed1997

[Influence of anemia on hemodynamic changes in patients with cirrhosis].

OBJECTIVE: The aim of this retrospective study was to evaluate the systemic and splanchnic hemodynamic changes induced by anemia in patients with cirrhosis. METHOD: 148 patients (Child-Pugh A: 46 patients, Child-Pugh B: 64 patients and Child-Pugh C: 38 patients) were included in the study. Anemia was defined by a blood hemoglobin level < 12 g/dL. A systemic and splanchnic hemodynamic study was performed in all patients. RESULTS: A significant elevation of the hepatic venous pressure gradient was observed in Child-Pugh A patients with anemia but not in Child-Pugh B and C patients. In the 2 latter groups, cardiac index was significantly increased and systemic vascular resistance decreased in patients with anemia. CONCLUSION: Anemia may worsen the hemodynamic changes associated with cirrhosis.

Adult↗
PubMed1996

Haemodynamic and hormonal responses to long-term inhibition of nitric oxide synthesis in rats with portal hypertension.

In portal hypertension, the role of the vasorelaxant nitric oxide (NO) in long-term splanchnic and systemic vascular tone regulation is unclear. This study examined the effects of long-term administration of a NO synthesis inhibitor on haemodynamics in portal hypertensive rats. Rats were randomly assigned to receive either water (placebo) or 100 mg/kg.day of oral N-nitro-L-arginine methylester (L-NAME) for 28 days. At 14 days, the portal vein was ligated in 10 rats from each group. At 28 days, splanchnic and systemic blood flows were measured in 20 normal and 20 portal vein stenosed rats. Plasma atrial natriuretic peptide (ANP) concentrations as well as plasma and urinary cyclic guanosine monophosphate (cGMP) levels were also measured. Porto-systemic shunts were measured in other portal vein stenosed animals that had or had not received L-NAME. Portal vein stenosed rats that received L-NAME had significantly lower portal tributary blood flow and percentages of portal-systemic shunting (7.3 +/- 0.5 versus 3.7 +/- 0.2 ml/min.100 g and 96 +/- 1 versus 68 +/- 5%, respectively) and higher hepatocollateral vascular resistance (147 +/- 10 versus 295 +/- 30 dyn.s.cm-5.100 g.10(3), respectively) than placebo portal vein stenosed rats. Portal pressure, ANP and cGMP levels did not differ between the groups. Arterial pressure was significantly higher and cardiac index lower after L-NAME than after placebo. Normal rats had similar but less marked L-NAME-induced responses than portal hypertensive rats. The presence of a long-term L-NAME-induced vasoconstriction in collateral vessels and splanchnic and systemic arterioles in portal vein stenosed rats indicates that a NO-mediated vasodilator tone may contribute to the development and the maintenance of collateral circulation as well as splanchnic and systemic vasodilation in portal hypertension. Moreover, the NO-mediated vasodilator tone in portal hypertensive animals seems to be increased.

Animals↗
PubMed1996

Hemodynamic and metabolic effects of terlipressin in patients with cirrhosis receiving a nonselective beta-blocker.

Terlipressin (Glypressin), a vasopressin analog, may be administered to patients with cirrhosis receiving a beta-adrenergic antagonist. Since terlipressin alone and beta-blockers alone both decrease portal pressure, a combination of these substances may have additional portal hypotensive effects. However, the negative side effects of terlipressin may be accentuated by long-term beta-blockade. Thus, the present study examined hemodynamic and metabolic responses to terlipressin in 12 patients receiving nonselective beta-blockers (propranolol or nadolol). Hemodynamics and oxygen (O2) -derived variables were measured prior to and 30 min after the administration (intravenous bolus) of terlipressin (1 to 2 mg, according to body weight). The hepatic venous pressure gradient and azygos blood flow significantly decreased (from 15.3 +/- 1.1 to 12.5 +/- 1.1 mm Hg, and from 0.6 +/- 0.1 to 0.5 +/- 0.1 liters/min, respectively). Arterial and pulmonary wedged pressures significantly increased. Heart rate, cardiac index, and O2 consumption were not significantly affected by terlipressin. In conclusion, in patients with cirrhosis being treated with a nonselective beta-blocker, terlipressin administration decreased portal pressure. Moreover, terlipressin induced only mild systemic hemodynamic effects in these patients. These results suggest that terlipressin can be administered in patients receiving a beta-adrenergic blocker.

Adrenergic beta-Antagonists↗
PubMed1996

Activation of maxi-K channels by parathyroid hormone and prostaglandin E2 in human osteoblast bone cells.

Patch clamp experiments were performed on two human osteosarcoma cell lines (MG-63 and SaOS-2 cells) that show an osteoblasticlike phenotype to identify and characterize the specific K channels present in these cells. In case of MG-63 cells, in the cell-attached patch configuration (CAP) no channel activity was observed in 2 mM Ca Ringer (control condition) at resting potential. In contrast, a maxi-K channel was observed in previously silent CAP upon addition of 50 nM parathyroid hormone (PTH), 5 nM prostaglandin E2 (PGE2) or 0.1 mM dibutyryl cAMP + 1 microM forskolin to the bath solution. However, maxi-K channels were present in excised patches from both stimulated and nonstimulated cells in 50% of total patches tested. A similar K channel was also observed in SaOS-2 cells. Characterization of this maxi-K channel showed that in symmetrical solutions (140 mM K) the channel has a conductance of 246 +/- 4.5 pS (n = 7 patches) and, when Na was added to the bath solution, the permeability ratio (PK/PNa) was 10 and 11 for MG-63 and SaOS-2 cells respectively. In excised patches from MG-63 cells, the channel open probability (Po) is both voltage- (channel opening with depolarization) and Ca-dependent; the presence of Ca shifts the Po vs. voltage curve toward negative membrane potential. Direct modulation of this maxi-K channel via protein kinase A (PKA) is very unlikely since in excised patches the activity of this channel is not sensitive to the addition of 1 mM ATP + 20 U/ml catalytic subunit of PKA. We next evaluated the possibility that PGE2 or PTH stimulated the channel through a rise in intracellular calcium. First, calcium uptake (45Ca2+) by MG-63 cells was stimulated in the presence of PTH and PGE2 an effect inhibited by Nitrendipine (10 microM). Second, whereas PGE2 stimulated the calcium-activated maxi-K channel in 2 mM Ca Ringer in 60% of patches studied, in Ca-free Ringer bath solution, PGE2 did not open any channels (n = 10 patches) nor did cAMP + forskolin (n = 3 patches), although K channels were present under the patch upon excision. In addition, in the presence of 2 mM Ca Ringer and 10 microM Nitrendipine in CAP configuration, PGE2 (n = 5 patches) and cAMP + forskolin (n = 2 patches) failed to open K channels present under the patch. As channel activation by phosphorylation with the catalytic subunit of PKA was not observed, and Nitrendipine addition to the bath or the absence of calcium prevented the opening of this channel, it is concluded that activation of this channel by PTH, PGE2 or dibutyryl cAMP + forskolin is due to an increase in intracellular calcium concentration via Ca influx.

Calcium↗
PubMed1996

[Indications and role of albumin, plasma volume expansion excluded, in the preoperative or postoperative management of portal hypertension].

Low serum albumin levels are common in patients with cirrhosis and liver failure. Decreased synthesis is the main but not the only mechanism leading to decreased serum levels. The consequences of low albumin concentrations are a decreased plasma colloid osmotic pressure and a decreased binding of liposoluble xenobiotics and endogenous substances. Besides the fluid accumulation in pleura and peritoneum, the complications directly related to low serum albumin levels have been only poorly assessed. An increase in serum albumin levels (by a few g.L-1) for a few days can be achieved by the infusion of large amounts of human albumin (approximately 120 g over 3 days). The efficacy of this treatment has been only tested in association with large paracentesis: albumin infusion, which induces volume expansion, reduced the incidence of hyponatremia and functional renal failure. No significant effect on ascites production rate or survival has been observed. Similar results were achieved through polygelin or dextran-70 infusions. No well-conducted controlled study on the value of albumin infusion in other circumstances apart from cirrhotic patients is available. In conclusion, albumin infusion should be reserved to the treatment of hyponatraemia or functional renal failure complicating cirrhosis with severe liver failure and marked hypoalbuminaemia, when the infusion of colloids failed to correct these anomalies.

Ascites↗
PubMed1996

Transjugular intrahepatic portosystemic shunts: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial. French Group of Clinicians and a Group of Biologists.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunts reduce portal pressure and can control ascites in patients with cirrhosis. We carried out a controlled study to evaluate this procedure for the management of refractory ascites in patients with cirrhosis and to clarify its mechanism of action. METHODS: Twenty-five patients with refractory ascites were included in the trial; 13 were randomly assigned to shunts and 12 to paracentesis. Four patients in each group were Child-Pugh class C and the others were class B. Follow-up ranged from 9 to 34 months. Hemodynamic values, liver and renal tests and neurohumoral factors were measured before and at 4 months after inclusion. RESULTS: Shunts were successfully placed in 10 out of 13 patients. At 4 months, ascites had improved in all class B patients in the shunt group and in none of the patients in the paracentesis group (p < 0.05); ascites did not improve in any of the class C patients in either of the groups. At 2 years, the overall survival rate was 29 +/- 13% (mean +/- SE) in the shunt group and 56 +/- 17% in the paracentesis group (p < 0.05). In class B patients, there was no significant difference in mortality. At 4 months, portal pressure was significantly lower than before the shunt, while plasma levels of atrial natriuretic peptide were significantly higher and plasma levels of renin and norepinephrine significantly lower. CONCLUSIONS: In this trial, intrahepatic shunts were effective on refractory ascites in patients with cirrhosis. However, the overall survival rate was lower in shunted patients than in those treated with paracentesis. The efficacy of intrahepatic shunts on ascites was only observed in class B patients. Survival did not improve in class B patients, and decreased in class C patients compared to paracentesis. The efficacy of shunts on ascites might be due to neurohumoral factors which control natriuresis and depend on hepatic sinusoidal pressure.

Ascites↗
PubMed1996

Hyporeactivity of mesenteric resistance arteries in portal hypertensive rats.

BACKGROUND/AIMS: Hyporesponsiveness to vasoconstrictors in portal hypertension has been shown to involve increased production of nitric oxide in large arteries in vitro. Small arteries (diameter 50-500 microns) are partly responsible for peripheral resistance and probably have different regulatory mechanisms from large arteries. The purpose of this study was to investigate the hyporeactivity of small mesenteric resistance arteries in portal hypertensive rats and to determine the role of nitric oxide and prostaglandins in this hyporesponsiveness. METHODS: Third branch mesenteric arteries from normal and portal hypertensive rats obtained by portal vein ligation were isolated and suspended in myographs for isometric tension recording. Reactivity to vasoconstrictors was assessed by dose-responses to phenylephrine (Phe 10(-8) to 10(-3) M) and by potassium chloride (KCl 45 mM). Acetylcholine (Ach 10(-5) M) was administered in pre-contracted KCl 45 mM arterial rings to evaluate endothelium-dependent relaxation. Pre-incubations with N-nitro-L-arginine (L-NNA 10(-4) M, a specific inhibitor of nitric oxide synthase, or with indomethacin (10(-5) M), a specific inhibitor of cyclo-oxygenase, were performed to compare the individual roles of nitric oxide and prostaglandins in KCl 45 mM-induced contractions. RESULTS: Impaired responses to Phe (3731 +/- 851 microN and 5971 +/- 745 microN, respectively; p < 0.05) and to KCl (2197 +/- 251 vs 2804 +/- 222 microN, respectively; p < 0.05) were observed in mesenteric resistance arterial rings from portal hypertensive rats compared to rings from normal rats. Ach-dependent relaxation did not significantly differ between normal (-25.7 +/- 5.1%) and portal hypertensive (-17.3 +/- 3.3%) rats. Indomethacin induced a similar significant increase in KCl-induced contraction in normal (3472 +/- 400 microN) and portal hypertensive (3432 +/- 654 rats. Nitric oxide synthesis inhibition had no effect in normal rats (3032 +/- 368 microN) but significantly increased KCl-induced contraction in portal hypertensive rats (3331 +/- 551 microN). CONCLUSION: These results demonstrate the existence of a hyporesponsiveness to vasoconstrictors in small mesenteric resistance arteries of portal hypertensive rats, which seems to be due to increased production of nitric oxide.

Acetylcholine↗
PubMed1996

Acute haemodynamic responses and inhibition of tumour necrosis factor-alpha by pentoxifylline in rats with cirrhosis.

1. Although pentoxifylline has been shown to reduce portal hypertension, the mechanism for this is unclear. Since pentoxifylline decreases tumour necrosis factor-alpha production and since this cytokine may induce vasodilatation per se, a pentoxifylline-induced decrease in tumour necrosis factor-alpha production may limit arterial vasodilatation and decrease portal pressure. The aim of the present study was to examine the effects of pentoxifylline administration on plasma tumour necrosis factor-alpha concentration and haemodynamics in normal and cirrhotic rats. 2. In both groups, systemic and splanchnic haemodynamics and plasma tumour necrosis factor-alpha concentrations were measured before and 120 min after the administration of saline or pentoxifylline (20 mg/kg intravenous bolus). 3. In cirrhotic rats, pentoxifylline significantly decreased portal pressure (24 +/- 13%) and tributary blood flow (33 +/- 30%). On the other hand, pentoxifylline significantly increased vascular resistance in portal and hepatic arterial territories. Systemic haemodynamics were not altered. In normal rats, pentoxifylline significantly decreased portal pressure but induced no other significant changes in splanchnic or systemic haemodynamics. In cirrhotic rats, plasma tumour necrosis factor-alpha concentrations were significantly reduced after pentoxifylline administration but not after saline administration. No significant correlations were found between pentoxifylline-induced changes in tumour necrosis factor-alpha levels and changes in splanchnic haemodynamics. In normal rats, plasma tumour necrosis factor-alpha concentrations significantly decreased after pentoxifylline or saline administration. 4. This study shows that in rats with cirrhosis, pentoxifylline induces a decrease in both portal pressure and plasma tumour necrosis factor-alpha concentrations. These reductions were not correlated however.

Animals↗
PubMed1996

Dose-dependent effects of a nitric oxide biosynthesis inhibitor on hyperdynamic circulation in two models of portal hypertension in conscious rats.

The role of nitric oxide (NO) in the hyperkinetic circulation in portal hypertension has not been clearly elucidated. Different doses of NO inhibitors, haemodynamic values and experimental conditions might explain the discrepant results. The aim of the present study was to investigate the acute effects of a specific biosynthesis inhibitor of NO, Nomega-nitro-L-arginine (L-NNA), on the systemic and splanchnic circulation in normal conscious rats and rats with portal hypertension due to either partial portal vein stenosis or secondary biliary cirrhosis. The administration of L-NNA (15 to 960 micrograms.kg-1.min-1) induced a significant dose dependent increase in arterial pressure which was not different among the three groups of rats. Following an acute and maximal vasopressive dose of L-NNA (1 mg.kg-1.min-1) cardiac index decreased more in portal vein stenosed and cirrhotic rats (-45 +/- 3% and -45 +/- 2%, respectively) than in normal rats (-31 +/- 2%), and systemic vascular resistance increased more in the two groups of portal hypertensive rats than in normals (+ 161 +/- 13% and + 154 +/- 10% vs + 85 +/- 6%, respectively). L-NNA caused a greater decrease in portal tributary blood flow in portal vein stenosed and cirrhotic rats (-63 +/- 4% and -55 +/- 4%, respectively) than in normal rats (-45 +/- 6%). Similarly, the increase in portal territory vascular resistance was significantly more marked in portal vein stenosed and cirrhotic rats (+ 337 +/- 62% and + 214 +/- 24%, respectively) than in normal rats (+ 153 +/- 23%). Portal pressure did not change. Following the acute administration of L-NNA, no significant difference in splanchnic and systemic haemodynamics were noted between portal vein stenosed and normal rats, except for portal pressure. In cirrhotic rats, splanchnic and systemic values remained different from normal rats. This study confirms that NO plays a role in the haemodynamic changes in portal hypertension, and shows that NO inhibitors have a dose-dependent effect in conscious portal hypertensive rats.

Animals↗
PubMed1996

Role of pentobarbitone anaesthesia and sympathetic tone in the haemodynamic effects of isosorbide dinitrate in rats with cirrhosis.

The haemodynamic effects of nitrovasodilators and their mechanisms of action on portal hypertension remain unclear. The splanchnic and systemic haemodynamic response to the infusion of isosorbide dinitrate (100 micrograms/kg per min), a nitrovasodilator, was investigated in cirrhotic rats. The role of the conscious state in the haemodynamic response to isosorbide dinitrate was examined using rats that were anaesthetized with pentobarbitone. The role of sympathetic tone in the haemodynamic response to isosorbide dinitrate was examined using rats pretreated with the ganglion blocker hexamethonium. Isosorbide dinitrate had no haemodynamic effects in conscious, unblocked normal and cirrhotic rats. Isosorbide dinitrate had no haemodynamic effects in normal and cirrhotic rats treated with hexamethonium. In normal anaesthetized rats, isosorbide dinitrate significantly decreased systemic vascular resistance (414 +/- 25 vs 290 +/- 26 dyn.s/cm-5 per 100 g). In cirrhotic anaesthetized rats, isosorbide dinitrate significantly decreased mean arterial pressure (98 +/- 6 vs 79 +/- 7 mmHg), systemic vascular resistance (318 +/- 30 vs 207 +/- 10 dyn.s/cm-5 per 100 g), portal pressure (14.0 +/- 1.0 vs 11.3 +/- 0.9 mmHg) and portal territory vascular resistance (1362 +/- 163 vs 1031 +/- 182 dyn.s/cm5 per 100 g). In conclusion, this study shows that the portal hypotensive effects of isosorbide dinitrate depend upon the alterations of vascular tone by pentobarbitone.

Adjuvants, Anesthesia↗
PubMed1996

Renal and haemodynamic responses to a novel kappa opioid receptor agonist, niravoline (RU 51,599), in rats with cirrhosis.

Because renal water retention is a complication of cirrhosis, niravoline (RU 51,599), a novel kappa (kappa) opioid receptor agonist which is known to cause a water diuresis under normal conditions, may be useful in the therapy of chronic liver diseases. Thus, the present study examined the effects of niravoline on renal function in rats with cirrhosis. Urine was collected during the 2 h period following the administration of vehicle (saline) in one groups of animals or niravoline (3 mg/kg, i.v.) in another group. Urinary and plasma osmolality were measured prior to and 2 h after niravoline in a third group of animals. Urine flow and natraemia were significantly higher after niravoline (147 +/- 12 microL/min and 153 +/- 2 mmol/L, respectively) than after vehicle (27 +/- 7 microL/min and 146 +/- 1 mmol/L, respectively). Niravoline significantly decreased urinary osmolality and significantly increased plasma osmolality and free water clearance. This substance did not significantly change urinary sodium excretion. In conclusion, this study shows that niravoline, a kappa opioid receptor agonist, induced a water diuresis in rats with cirrhosis.

Animals↗
PubMed1996

Role of sympathetic cardiovascular tone in control of arterial pressure in rats with cirrhosis.

Although an increase in sympathetic nervous activity has been recognized in cirrhosis, the contribution of this overactivity to the regulation of arterial pressure is unknown. The arterial pressure response to increasing doses of hexamethonium (0.05 to 3.2 mg.kg-1.min-1), a ganglionic blocker that decreases sympathetic cardiovascular tone, was explored in normal rats and in two models of portal hypertension, i.e., rats with cirrhosis and rats with portal vein stenosis. Changes in plasma norepinephrine concentrations were greater in rats with cirrhosis (356 +/- 50 vs 166 +/- 30 pg/ml, p = 0.04) than in normal rats (186 +/- 23 vs 86 +/- 31 pg/ml, p = 0.06) and rats with portal vein stenosis (103 +/- 37 vs 93 +/- 5 pg/ml, p = 0.10). The maximum decrease in arterial pressure was obtained at a dose of 1.6 mg.kg-1.min-1 in each group. However, the decrease in arterial pressure was significantly greater in rats with cirrhosis (-25 +/- 2%) than in normal rats (-11 +/- 1%) and in rats with portal vein stenosis (-13 +/- 2%) (p = 0.04). In conclusion, the results of this study suggest that the sympathetic cardiovascular tone is more important for the maintenance of arterial pressure in rats with cirrhosis than in normal rats and in rats with portal vein stenosis.

Animals↗
PubMed1996

Systemic and splanchnic hemodynamic changes in patients with hepatic schistosomiasis.

Although hepatic schistosomiasis is a common cause of portal hypertension, only a few hemodynamic studies, in humans, have been published on this subject. The aim of this study was to determine the systemic and splanchnic hemodynamic changes in hepatic schistosomiasis and to evaluate the influence of liver fibrosis on these changes. A retrospective analysis of a series of 13 patients with hepatic schistosomiasis who had undergone hemodynamic studies was performed. Portal or perisinusoidal fibrosis was present at liver biopsy in 8 patients. The control group included 22 patients with chronic hepatitis and normal hepatic venous pressure gradients. Patients with schistosomiasis exhibited high cardiac index (4.11 +/- 1.15 l.min-1.m-2 vs 2.99 +/- 0.85 l.min-1.m-2; p < 0.05) and low systemic vascular resistance (1039 +/- 316 dyn.s.cm-5 vs 1334 +/- 336 dyn.s.cm-5; p < 0.05). The hepatic venous pressure gradient and hepatic blood flow were normal. Azygos blood flow was markedly increased (0.90 +/- 0.66 l.min-1 vs 0.13 +/- 0.04 l.min-1; p < 0.05). Hemodynamic values were not significantly different between patients with liver fibrosis and those without fibrosis at liver biopsy. In conclusion, patients with hepatic schistosomiasis had a hyperkinetic systemic and splanchnic circulation. In patients with esophageal varices, a normal hepatic venous pressure gradient confirmed presinusoidal portal hypertension. The presence of portal or perisinuoidal fibrosis did not influence hyperdynamic splanchnic state.

Adult↗