Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma endothelin concentrations are elevated in cirrhosis and correlate with disease severity. This study assessed forearm vascular responses to exogenous endothelin-1 (ET-1), and evaluated the contribution of endogenous ET-1 to the maintenance of basal peripheral vascular tone in patients with well-compensated cirrhosis (n = 11) and matched healthy controls (n = 8). Bilateral forearm blood flow (FBF) was measured at baseline and following unilateral, subsystemic, intrabrachial artery infusions of ET-1 (2 and 6 pmol/min); BQ-123, a selective ET(A) receptor antagonist (3 and 10 nmol/min); and BQ-788, a selective ET(B) receptor antagonist (0.3 and 1 nmol/min) using venous occlusion plethysmography. Baseline systemic hemodynamics and plasma ET-1 and big ET-1 concentrations were measured using electrical bioimpedance and radioimmunoassay, respectively. Patients and controls had similar baseline FBF, systemic hemodynamics, and plasma ET-1 and big ET-1 concentrations. In both groups, ET-1 and BQ-788 caused significant vasoconstriction (P < .001) and BQ-123 caused significant vasodilatation (P < .001). Compared with controls, cirrhotic patients had attenuated ET-1 responses (P < .001), augmented BQ-123 responses (P < .001), and similar BQ-788 responses (P = .62). Despite normal systemic hemodynamics and plasma ET-1 concentrations, forearm vascular responses to exogenous ET-1 are reduced in cirrhotic patients. The augmented vasodilatation to BQ-123 in cirrhotic patients is consistent with a compensated vasodilated state, and a greater contribution of ET-1 to the maintenance of basal vascular tone acting through the ET(A) receptor.
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PMID:Altered peripheral vascular responses to exogenous and endogenous endothelin-1 in patients with well-compensated cirrhosis. 1128 46

The role of circulating endothelin- , a potent vasoconstricting peptide, in liver cirrhosis is still controversial. It has been postulated that endothelin-1 may play a role in the circulatory derangement occurring in cirrhotic subjects, and increased plasma endothelin-1 levels have been reported in these patients. In this study we looked for a relationship between the severity of the liver disease according to Child's classification and plasma endothelin-1 concentrations in a group of cirrhotic patients compared with a healthy control group. Twenty-two cirrhotic patients and 10 healthy controls, matched for sex and age, were selected for study after informed consent. The etiology of cirrhosis was posthepatitis B in 8 of 22 cases, posthepatitis C in 13 of 22 cases, and alcoholism in 1 patient. According to Child's classification, 6 patients were in class A, 6 in class B, and 10 in class C. Plasma endothelin-1 was measured by a commercial RIA kit (Amersham UK). Mean +/- SD plasma endothelin-1 levels were 8.8 +/- 0.9 pg/ml in controls and 9.2 +/- 1.1 pg/ml in all cirrhotic patients (P > 0.05). In each sub-group of cirrhotics, plasma endothelin- was 8.6 +/- 1.2 pg/ml in Child A, 8.9 +/- 1.9 pg/ml in Child B, and 10.6 +/- 1.5 pg/ml in Child C groups, respectively. There were no statistical differences between control subjects and Child A and B cirrhotic patients (P > 0.05). A significant increase in endothelinl was observed only in the Child C group versus either group A or B (P = 0.004). Our results show that alterations of circulating endothelin-1 do not occur in all cirrhotic patients; higher plasma levels than controls are only detectable in patients with more-severe hepatic failure. We do not know whether increased endothelin-1 levels are a consequence of hemodynamic disorders occurring in the advanced phase of liver cirrhosis or play a pathogenic role.
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PMID:Plasma endothelin-1 levels in liver cirrhosis. 1128 6

Plasma concentrations of endothelin-1 (ET-1) and nitrite/nitrate of patients with portal hypertension were measured. Sixteen patients with liver cirrhosis (the LC group) and 14 patients with idiopathic portal hypertension (the IPH group) and 12 healthy subjects (normal controls) were included in this study. The peripheral venous plasma concentration of ET-1 was significantly higher in the LC group (6.69+/-2.44 pg/ml) than in the IPH group (3.07+/-0.84 pg/ml) and normal controls (1.79+/-0.36 pg/ml), while the value in the IPH group was also significantly higher than that in normal controls. The peripheral venous plasma concentration of nitrite/nitrate was significantly higher in the LC group (67.7+/-38.9 &mgr;Mol/l) than in the IPH group (32.3+/-24.4 &mgr;Mol/l) and normal controls (26.1+/-9.8 &mgr;Mol/l). Hepatic venous plasma concentrations of ET-1 and nitrite/nitrate were measured in 8 patients from the LC group and 10 patients from the IPH group. The plasma concentration of ET-1 in the hepatic vein was significantly higher than that in the peripheral vein in both the LC and the IPH groups. The plasma concentration of nitrite/nitrate in the hepatic vein was significantly higher than that in the peripheral vein in the LC group. We also investigated the localization of ET-1, endothelin receptor (ET receptor) and nitric oxide synthase (NOS) in the liver tissue of LC patients (n=10), IPH patients (n=10) and normal controls (n=10). The expressions of ET-1, ET A receptors, ET B receptors, and inducive NOS (iNOS) were detected in patients with LC, and the labeling index (LI) was significantly higher than that in patients with IPH and normal controls. The expressions of ET-1, ET A receptors, and ET B receptors were found in patients with IPH, and the LI was significantly higher than that in normal controls. The expression of endothelial NOS (eNOS) was scarce in both LC and IPH patients. From these results, overproduction of ET-1 in the liver was regarded as one of the causes of the high plasma concentration of ET-1 in patients with LC and IPH. One of the causes of the high plasma concentration of nitrite/nitrate in LC was considered to be overproduction of nitric oxide (NO) in the liver. And we suggested that ET-1 is at a relatively higher density than NO in the hepatic sinusoid in LC and IPH.
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PMID:Clinical investigation of endothelin-1 and nitric oxide in patients with portal hypertension focusing on plasma levels and immunohistological staining of liver tissues. 1147 Jun 27

Patients with cirrhosis and portal hypertension exhibit characteristic haemodynamic changes with a hyperkinetic systemic circulation, abnormal distribution of the blood volume, and neurohumoral dysregulation. Moreover, the circulating levels of several vasoactive substances may be elevated. Splanchnic vasodilatation is of pathogenic significance for the low systemic vascular resistance and abnormal volume distribution, which are important elements in the development of the concomitant cardiac dysfunction, recently termed cirrhotic cardiomyopathy. The systolic and diastolic functions are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms seem to include a reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling, and conductance abnormalities. Various vasodilators. such as nitric oxide and calcitonin gene-related peptide, are among candidates in the vasodilatation and the increased arterial compliance recently described in advanced cirrhosis. Reflex-induced enhanced sympatho-adrenal activity, activation of the renin-angiotensin-aldosterone system, and elevated circulating vasopressin and endothelin-1 are implicated in the haemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the haemodynamic and neurohumoral abnormalities in cirrhosis are part of a general cardiovascular dysfunction influencing the course of the disease, with reduction of organ function and sodium-water retention as the outcome. These aspects are relevant to therapy.
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PMID:Vasoactive substances in the circulatory dysfunction of cirrhosis. 1168 31

Aims of this study are to analyze the influence of endothelin-1 (ET-1) on hemodynamic evolution during liver transplantation (LT) and study the role of a temporary portacaval shunt in ET-1 synthesis. Forty LTs in patients with cirrhosis were studied. Two groups were analyzed: the first group had a temporary portacaval shunt during the anhepatic phase, and the second group did not. Portal and systemic ET-1 levels were measured at several times. At the end of the anhepatic phase, systemic (16.1 +/- 6.5 pg/mL) and portal (19.2 +/- 7 pg/mL) ET-1 levels increased, whereas they decreased after reperfusion (systemic, 11.8 +/- 7.1 pg/mL; portal, 13.2 +/- 6.8 pg/mL). Portal flow at the beginning of LT correlated with systemic ET-1 levels (R2 = 0.3; P =.004). A temporary portacaval shunt reduced portal pressure during the anhepatic phase, but did not modify ET-1 levels. Patients with reperfusion syndrome had greater systemic ET-1 levels in the anhepatic phase (19.1 +/- 6.9 v 15.1 +/- 6.1 pg/mL; P =.07). Although there is a relationship between ET-1 levels and portal flow and reperfusion syndrome, no clear clinical effect on hemodynamics could be shown. Creation of a portacaval shunt made no change in ET-1 levels.
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PMID:Influence of endothelin-1 on hemodynamics during liver transplantation with and without temporary portocaval shunt: results of a clinical randomized study. 1179 82

Accumulated experimental and clinical data suggest that adrenocorticosteroids and/or endogenous ouabain-like substances may play an important role in the mechanism of furosemide diuretic action. It was reported that the drug is highly bound in the adrenals, lungs, kidney, spleen, and liver. In patients with liver cirrhosis, furosemide exerted a markedly decreased natriuretic effect compared with normal subjects, and the plasma levels of circulating endothelin and atrial natriuretic factor (ANF) were significantly elevated. In neonates, after administration of furosemide, the urinary excretion of endothelin-1 and aldosterone increased markedly, and it is known that endothelin may release ANF and aldosterone in a dose-dependent manner. Furosemide was used to stimulate zona glomerulosa, whereas ANF decreased the production of steroids in zona glomerulosa and fasciculata cell culture owing to stimulation by various factors. Because the concomitant use of ANF and furosemide appeared to be diuretically effective in newborns after cardiac surgery, one may suggest that furosemide competes with ANF for its effects on the adrenals. Furosemide administered by inhalation exerted a protective effect on allergic and perennial nonallergic rhinitis and was effective in preventing the postsurgical recurrence of nasal polyposis. The drug can also be used as an antiasthmatic agent. In preterm ventilator-dependent infants with chronic lung disease, aerosolized furosemide improved pulmonary function with no marked effect on diuresis. In adults and children with asthma, furosemide exerted a protective effect against bronchoconstriction induced by several indirect stimuli similar to that of disodium cromoglycate or nedocromil. Aerosolized furosemide had a preventive effect also on bronchoconstriction induced by inhaled lysine acetylsalicylate in patients with aspirin-sensitive asthma. In high-dose beclomethasone-dependent asthma, inhaled lysine acetylsalicylate and furosemide exerted a mutually potentiating antiasthmatic activity, allowing considerable sparing of the inhaled steroid. It is proposed that this effect may be explained by the corticosteroid-sparing action of lysine released from the lysine acetylsalicylate molecule because similar beneficial effects were also obtained after the concomitant use of epsilon-aminocaproic acid (whose chemical structure is almost the same as that of lysine) and prednisone. Furosemide exhibited an anti-inflammatory effect through inhibition of production and release of cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha from peripheral mononuclear cells, which may have a beneficial effect on local inflamed tissue imbalance in the ratio of different cytokines, thus improving the sensitivity of target cells to endogenous glucocorticosteroids.
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PMID:Furosemide: progress in understanding its diuretic, anti-inflammatory, and bronchodilating mechanism of action, and use in the treatment of respiratory tract diseases. 1211 21

BACKGROUND/AIMS: Bacterial infections are known to trigger renal failure in patients with cirrhosis. However, the mechanisms for this process are unclear. The aim of this study was to investigate the role of endothelin-1 (ET-1) in a cirrhotic rat model with endotoxin induced renal failure by mixed ET-1 receptor antagonist, bosentan. METHODS: Cirrrhosis was induced by twice weekly intraperitoneal injections of CCl(4) together with phenobarbital in drinking water. Cirrhotic and non-cirrhotic rats were either pretreated with physiological saline or bosentan prior to administration of low dose endotoxin. Urine and blood samples were then collected within a period of 3 h for the estimation of ET-1, NO(3)(-)/NO(2)(-) levels ( nitric oxide metabolites: NO(x)) and renal function tests. RESULTS: Cirrhotic rats had higher ET-1 and NO(x) levels in comparison with non-cirrhotic rats. Endotoxin administration to cirrhotic rats led to the deterioration of the renal function, and elevation of plasma ET-1 and NO(x) levels. Bosentan pretreatment prior to endotoxin administration caused an increase in the urine volume and creatinine clearance of cirrhotic rats, but had no effect on Na(+) excretion. CONCLUSION: ET-1 has a significant role in endotoxin induced renal impairment in cirrhotic rats, and ET-1 receptor antagonism provides partial protection of the renal function.
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PMID:Role of endothelin-1 in a cirrhotic rat model with endotoxin induced acute renal failure. 1227 Jul 40

BACKGROUND: In cirrhotic livers, the balance of vasoactive substances is in favour of vasoconstrictors with relatively insufficient nitric oxide. Endothelial dysfunction has been documented in cirrhotic rat livers leading to a lower activity of endothelial nitric oxide synthase but this might not be sufficient to explain the low nitric oxide presence. We compared the amount of all nitric oxide synthase isoforms and other factors that influence nitric oxide bioavailability in livers of two portal hypertensive rat models: prehepatic portal hypertension and carbon tetrachloride induced cirrhosis, in comparison with healthy controls. RESULTS: Endothelial nitric oxide synthase was the solely detected isoform by Western blotting in all livers. In cirrhotic livers, the amount of endothelial nitric oxide synthase protein was lower than in healthy controls, although an overlap existed. Levels of caveolin-1 messenger RNA were within the normal range but endothelin-1 messenger RNA levels were significantly higher in cirrhotic livers (p < 0.05). A markedly lower superoxide dismutase activity was observed in cirrhotic livers as compared to healthy controls (p < 0.05). CONCLUSIONS: In contrast to prehepatic portal hypertension, cirrhotic livers had decreased endothelial nitric oxide synthase protein and enhanced endothelin-1 messenger RNA amount. We hypothesise that a vasodilator/vasoconstrictor imbalance may be further aggravated by the reduced activity of superoxide dismutase. Decreased activity allows enhanced superoxide action, which may lead to breakdown of nitric oxide in liver sinusoids.
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PMID:Low NO bioavailability in CCl4 cirrhotic rat livers might result from low NO synthesis combined with decreased superoxide dismutase activity allowing superoxide-mediated NO breakdown: A comparison of two portal hypertensive rat models with healthy controls. 1257 97

The effects of Orthotopic liver transplantation (OLT) on renal function and major vasoactive factors was assessed in end-stage cirrhotic patients. Renal function, mean arterial pressure, and plasma vasoactive hormones were measured In 22 cirrhotic patients with refractory ascites before and after OLT. Before OLT, mean arterial pressure, glomerular filtration rate, free water clearance, and fractional sodium excretion serum sodium levels were decreased. In addition, serum creatinine and plasma levels of vasoactive factors were increased. Ten of these patients fulfilled criteria of hepatorenal syndrome (HRS). Nine to 12 months after transplantation, renal function had improved and plasma levels of vasoactive factors had decreased significantly in all patients, including those with HRS. However, glomerular filtration rate remained subnormal and plasma endothelin-1 levels and plasma renin activity remained increased in most of them. In conclusion, OLT improves renal function in patients with end-stage liver cirrhosis, including those with HRS. However, renal function remains subnormal in most of these patients.
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PMID:Effects of orthotopic liver transplantation on vasoactive systems and renal function in patients with advanced liver cirrhosis. 1264 7

Within the colonic mucosa of rats with portal hypertension and liver cirrhosis, there is an increased generation of inflammatory mediators, such as leukotriene B4 and endothelin-1, and increased generation of nitric oxide. Nitric oxide overproduction may induce tissue injury. This study was undertaken to assess whether the colonic mucosa of rats with portal hypertension and liver disease have increased susceptibility to damage by noxious agents. In this study, acetic acid colitis was induced in rats with portal vein ligation and in control groups, and iodoacetamide colitis was induced in rats with partial portal vein ligation and cirrhosis due to bile duct ligation and in control groups. Rats with acetic acid colitis and those with iodoacetamide-induced colitis were studied 24 and 72 hours, respectively, after induction of colitis. Portal hypertension alone and portal hypertension with cirrhosis were present in the portal vein ligation and bile duct ligation models, respectively. In the rats with acetic acid, colitis lesion area, colonic mucosal myeloperoxidase activity, and prostaglandin E2 generation were not different between the portal vein ligation groups with and without colitis. Nitric oxide activity was higher only in the groups with colitis, irrespective of the presence of portal hypertension. In the group of rats with iodoacetamide colitis, colonic lesion area and colonic mucosal myeloperoxidase activity were similar in all groups with colitis. Colonic mucosal prostaglandin E2 generation was lower in the portal vein ligation and bile duct ligation rats with colitis compared with a control group. We concluded that rats with experimental portal hypertension do not have increased damage when induced by either acetic acid or iodoacetamide.
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PMID:Experimental colitis in rats with portal hypertension and liver disease. 1265 33


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