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

Endothelin-1, a potent vasoconstrictor peptide with 21 amino acid residues, is released by the vascular endothelium. Plasma immunoreactive endothelin levels were measured in 23 patients with cirrhosis and in 20 healthy subjects. Concentrations were significantly lower in patients with non-uraemic cirrhosis than in normal subjects (19.4 +/- 8.9 pmol/l vs. 48.8 +/- 24.8 pmol/l, p less than 0.002). Plasma renin, aldosterone, atrial natriuretic peptide, arginine-vasopressin and catecholamines did not show significant correlations with plasma endothelin-1 levels. Furthermore, there were no significant differences in plasma endothelin levels for etiology of cirrhosis, presence of ascites or varices. These data suggest that low circulating endothelin may be involved in the development or maintenance of systemic vasodilatation in cirrhosis.
 ...
PMID:Plasma endothelin levels in cirrhotic subjects. 138 39

Plasma concentrations of the recently isolated potent vasoconstrictory peptide endothelin were measured in 382 patients. The investigations were performed by means of a sensitive radioimmunoassay specific for Endothelin-1, 2. The results from 110 healthy volunteers displayed a normal range of 44.67 +/- 3.51 pg/ml. Significantly raised levels were found in 33 patients with chronic end-stage renal failure both before and after hemodialysis. In contrast, 35 patients with compensated renal insufficiency did not differ from the normals. Sixty-five patients after kidney transplantation revealed significantly elevated levels, as did 27 patients with acute myocardial infarction, 8 after coronary bypass surgery, and 5 with liver cirrhosis. The mean values of 27 patients with untreated hypertension, 22 with secondary hypertension, of various causes and 16 with coronary artery disease were comparable to the normal population. The values were significantly decreased in 9 pregnant women with hypertension and proteinuria. A marked decline was found in 5 patients with systemic lupus erythematodes, while 20 patients with rheumatoid arthritis demonstrated only a slight decrease. The pathophysiological role of endothelin as a local or circulating hormone in regulating systemic blood pressure or release of other hormones remains to be determined.
 ...
PMID:[Plasma endothelin in normal probands and patients with nephrologic-rheumatologic and cardiovascular diseases]. 221 2

To determine the clinical significance of plasma endothelin-1 in chronic liver disease, these levels were measured by radioimmunoassay. The plasma endothelin-1 levels in patients with cirrhosis (N = 16) (2.04 +/- 0.25 pg/ml) and patients with hepatocellular carcinoma (N = 22) (2.23 +/- 0.17 pg/ml) increased significantly compared with controls (N = 16) (1.17 +/- 0.17 pg/ml) and patients with chronic hepatitis (N = 11) (1.09 +/- 0.19 pg/ml) (P < 0.01). The presence of ascites rather than tumor volume was associated with a significant elevation of endothelin-1. Endothelin-1 showed significant negative correlations with parameters of hepatic function, including indocyanine green clearance, serum albumin, and prothrombin time. Although endothelin-1 was not correlated with plasma renin activity and plasma endotoxin, it demonstrated a significant positive correlation with the plasma level of atrial natriuretic peptide (r = 0.42, P < 0.01). These findings demonstrate that plasma endothelin-1 increased in proportion to the severity of liver damage and may be causally related with the derangement of systemic/renal hemodynamics and fluid and electrolyte homeostasis seen in advanced liver disease.
 ...
PMID:Clinical significance of plasma endothelin-1 in patients with chronic liver disease. 799 94

Endothelin-1 (ET-1), the most powerful agent to cause constriction of the hepatic vasculature, is synthesized in the liver by sinusoidal endothelial cells. Circulating ET-1 levels have been shown to increase in liver cirrhosis. As liver could be a major source of increased plasma ET-1 as well as a target for its pathologic actions, this study was designed to determine hepatic ET-1 and ET receptor(s) in experimental liver cirrhosis. Cirrhosis was induced in rats by intraperitoneal administration of carbon tetrachloride for 8 weeks. Hepatic ET-1 was measured by radioimmunoassay and ET receptors were determined by radioligand competition binding procedure. A four fold increase in ET-1 concentration accompanied by a 65% increase in ET-receptor density was observed in the cirrhotic liver. There was no change in the ET receptor affinity. The capacity of the liver to metabolize ET-1 was reduced significantly in cirrhosis. Interestingly, transforming growth factor-beta, hepatic levels of which increase in cirrhosis, stimulated ET-1 synthesis in cultured Ito cells. It has been shown that ET-1 is a potent constrictor of Ito cells that proliferate and transform into highly contractile myofibroblasts in liver cirrhosis. Thus, interactions between ET-1 and Ito cells may have significant implications in the pathogenesis and complications of liver cirrhosis.
 ...
PMID:Increased hepatic endothelin-1 levels and endothelin receptor density in cirrhotic rats. 862 11

Hepatic stellate cells are similar to tissue pericytes and have been shown to be contractile. In this study, we examined the effects of known mediators of stellate cell contraction on portal pressure in rat livers after carbon tetrachloride induced injury (including cirrhosis) and investigated the contractility of stellate cells as a function of liver injury. Sarafotoxin S6C, an endothelin B (ETB) receptor agonist, had minor effects on portal pressure when perfused into normal livers at concentrations known to elicit stellate cell contraction (2 nmol/L). In contrast, both endothelin-1 (2 nmol/L) and angiotensin II (8.6 nmol/L) caused a rapid and pronounced rise in portal pressure. The effects of sarafotoxin S6C (a potent stellate cell contractile agonist) on portal pressure were greater in cirrhotic than normal liver, whereas those of angiotensin II were unchanged after liver injury. Endothelin-1 and sarafotoxin S6C induced contractility of stellate cells increased in proportion to the degree of liver injury. Contractility was greatest for stellate cells isolated from cirrhotic livers, a population of cells that displayed the most activated phenotype, as measured by immunoblot of smooth muscle alpha actin. Autoradiography of cirrhotic livers after perfusion with 125I-endothelin-1 revealed binding to cells in both sinusoidal spaces and collagenous fibrotic bands, consistent with known locations of stellate cells. Finally, the mixed endothelin-A (ETA) and ETB receptor antagonist, bosentan, reduced portal pressure in portal hypertensive animals, consistent with its inhibitory effect on stellate cell contraction. We conclude that stellate cell contractility increases with progressive liver injury and is proportional to the degree of stellate cell activation, becoming most prominent in the cirrhotic liver. Endothelin-stimulated contraction of stellate cells in cirrhotic liver may contribute to increased intrahepatic resistance and portal pressure.
 ...
PMID:Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance. 870 68

Endothelin-1 belongs to a family of potent vasoconstrictors, recently isolated from endothelial cells. Endothelin-1 has a variety of hepatic effects and hepatic clearance from the circulation is important. Elevated plasma concentrations of Endothelin-1 are found after orthotopic liver transplantation and in cirrhosis with ascites. This study in piglets on hepatic bloodflow was designed to compare differences in effects between central venous and intraportal injection of endothelin-1, and to evaluate effects of repeated injections. Central venous injection of endothelin-1 caused a larger reduction in portal vein flow, while intraportal injection caused a larger increase in portal vein pressure. Repeated injections resulted in a reduction in portal vein flow and an increase in portal vein vascular resistance.
 ...
PMID:Effects of endothelin-1 on hepatic blood flow. 872 56

Endothelin-1 (ET-1) is involved in the pathogenesis of a number of diseases, including wound healing. In cirrhosis, the wounding response of the liver, circulating ET-1 levels are elevated; moreover, ET-1 has potent effects on hepatic stellate cells, the key effectors of cirrhosis. In this study, we have examined the regulatory role of ECE-1, a critical enzyme involved in ET-1 synthesis, in the two major cellular sources of hepatic ET-1. ET-1 release from normal hepatic endothelial cells was 25-fold higher than that from normal stellate cells. However, after liver injury, ET-1 release was increased in stellate cells but markedly decreased in endothelial cells. The two major isoforms of ECE-1, ECE-1alpha/1beta, made up 80% and 20%, respectively, of total ECE-1 in both stellate and endothelial cells. Following liver injury, ECE-1alpha mRNA was decreased by 44.2% in stellate cells, and by 16.1% in endothelial cells. ECE-1beta mRNA expression remained unchanged after injury. In contrast to ECE-1 mRNA, ECE-1 protein expression was increased by 43.9% in stellate cells but decreased in endothelial cells, while relative ECE-1 enzymatic activity was unchanged. In mRNA stability experiments, the half-life of ECE-1alpha mRNA in normal stellate cells was 13 h compared with 38 h in cells from injured livers. Thus, during hepatic wound healing, differential regulation of ECE-1 mRNA and protein appears to be critical in controlling ET-1 production.
 ...
PMID:Regulation of endothelin-1 synthesis by endothelin-converting enzyme-1 during wound healing. 991 64

Liver failure represents a major therapeutic challenge, and yet basic pathophysiological questions about hepatic perfusion and oxygenation in this condition have been poorly investigated. In this study, hepatic blood flow (HBF) and splanchnic oxygen delivery (DO2, sp) and oxygen consumption (VO2,sp) were assessed in patients with liver failure defined as hepatic encephalopathy grade II or more. Measurements were repeated after high-volume plasmapheresis (HVP) with exchange of 8 to 10 L of plasma. HBF was estimated by use of constant infusion of D-sorbitol and calculated according to Fick's principle from peripheral artery and hepatic vein concentrations. In 14 patients with acute liver failure (ALF), HBF (1.78 +/- 0.78 L/min) and VO2,sp (3.9 +/- 0.9 mmol/min) were higher than in 11 patients without liver disease (1.07 +/- 0.19 L/min, P <.01) and (2.3 +/- 0.7 mmol/min, P <.001). In 9 patients with acute on chronic liver disease (AOCLD), HBF (1.96 +/- 1.19 L/min) and VO2,sp (3.9 +/- 2.3 mmol/min) were higher than in 18 patients with stable cirrhosis (1.00 +/- 0.36 L/min, P <.005; and 2.0 +/- 0.6 mmol/min, P <.005). During HVP, HBF increased from 1.67 +/- 0.72 to 2.07 +/- 1.11 L/min (n=11) in ALF, and from 1.89 +/- 1.32 to 2.34 +/- 1.54 L/min (n=7) in AOCLD, P <.05 in both cases. In patients with ALF, cardiac output (thermodilution) was unchanged (6.7 +/- 2.5 vs. 6.6 +/- 2.2 L/min, NS) during HVP. Blood flow was redirected to the liver as the systemic vascular resistance index increased (1,587 +/- 650 vs. 2, 020 +/- 806 Dyne. s. cm-5. m2, P <.01) whereas splanchnic vascular resistance was unchanged. In AOCLD, neither systemic nor splanchnic vascular resistance was affected by HVP, but as cardiac output increased from 9.1 +/- 2.8 to 10.1 +/- 2.9 L/min (P <.01) more blood was directed to the splanchnic region. In all liver failure patients treated with HVP (n=18), DO2,sp increased by 15% (P <.05) whereas VO2,sp was unchanged. Endothelin-1 (ET-1) and ET-3 were determined before and after HVP. Changes of ET-1 were positively correlated with changes in HBF (P <.005) and VO2,sp (P <.05), indicating a role for ET-1 in splanchnic circulation and oxygenation. ET-3 was negatively correlated with systemic vascular resistance index before HVP (P <.05) but changes during HVP did not correlate. Our data suggest that liver failure is associated with increased HBF and VO2, sp. HVP further increased HBF and DO2,sp but VO2,sp was unchanged, indicating that splanchnic hypoxia was not present.
 ...
PMID:Hepatic blood flow and splanchnic oxygen consumption in patients with liver failure. Effect of high-volume plasmapheresis. 991 9

Octreotide is effective during 48 h in the treatment of acute variceal bleeding, probably by reducing variceal blood flow and pressure. Its basal and postprandial effects on splanchnic and systemic hemodynamics, and hormonal changes over this time interval have not yet been studied. Twenty-four patients with cirrhosis and portal hypertension were randomized to receive a liquid meal and either octreotide (Oct, 100 microg bolus intravenous, followed after 2 h by a continuous infusion of 25 microg/hr for 20 hr) or placebo (Plac) given at three consecutive days. Splanchnic (Doppler ultrasound) and systemic hemodynamics (noninvasive cardiac monitoring) were assessed on four consecutive days (one control day and three treatment days) during 2 hr. The postprandial increase in mean blood velocity of the superior mesenteric artery (SMA-V(mean) +44%), portal blood velocity (PV-V(mean), +44%) and total hepatic blood flow (HBF, +40%) observed in the placebo group during the control day was abolished during the first day of treatment (SMA-V(mean), +3%, P < 0.01; PV-V(mean), +6%, P < 0.05; HBF, -25%, P < 0.01) and still reduced after 48 hr in the octreotide group (SMA-V(mean) +28%, P < 0.05; PV-V(mean), +22%, P > 0.05; HBF, -8%, P < 0.05). The postprandial increase in cardiac index (CI, + 10%) and decrease in systemic vascular resistance index (SVRI, -6%) were blunted after the initial injection of octreotide only (CI, -8%, P < 0.05; SVRI, +18%, P < 0.01). Endothelin-1-levels, which were increased at baseline (Plac 25 +/- 17, Oct 16 +/- 13 ng/liter, P > 0.05) decreased significantly after 48 hr of treatment with octreotide (Plac 27 +/- 20, Oct 8 +/- 4 ng/liter, P < 0.05). Octreotide is effective during 48 hr in the prevention of postprandial hyperemia in cirrhotics, even if its efficacy is decreasing over time. Moreover it may have positive effects on systemic vasodilation in cirrhotics. These findings suggest a potential role of this drug in the chronic treatment of portal hypertension.
 ...
PMID:48-hour hemodynamic effects of octreotide on postprandial splanchnic hyperemia in patients with liver cirrhosis and portal hypertension: double-blind, placebo-controlled study. 1079 71

Endothelin-1 (ET-1) may mediate increased resistance to hepatic sinusoidal blood flow. We evaluated the hepatic distribution of ET-1 in patients with idiopathic portal hypertension (IPH), in which liver architecture may be normal, and in patients with cirrhosis, in which distortion of hepatic sinusoidal architecture is prominent. Immunohistochemistry and in situ hybridization were used to localize ET-1 in hepatic tissue of patients with IPH and cirrhosis. ET-1 was measured in plasma from a peripheral vein, the hepatic vein, and the portal vein of patients with cirrhosis of the liver and controls. On immunohistochemistry and in situ hybridization, ET-1 was localized to periportal hepatocytes and sinusoidal cells in patients with IPH and cirrhosis. Minimal positive staining for ET-1 was observed in control livers. Plasma ET-1 levels were significantly greater in patients with cirrhosis than in controls. In patients with cirrhosis, ET-1 was greater in the hepatic vein compared with the portal vein. However, the level of plasma ET-1 in patients with cirrhosis did not correlate with either the presence of ascites or portacaval pressure gradient. We conclude that in IPH, ET-1 is localized to sites in which it can modulate intrahepatic resistance. In late stages of cirrhosis, ET-1 may not modulate resistance. We speculate that vascular resistance in late stages of cirrhosis probably results from distortion of hepatic architecture.
 ...
PMID:Hepatic localization of endothelin-1 in patients with idiopathic portal hypertension and cirrhosis of the liver. 1098 59


1 2 Next >>