UMLS:C0023890 - FACTA Search

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Query: UMLS:C0023890 (cirrhosis)
42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impaired ability to excrete a water load occurs in a substantial number of patients with advanced cirrhosis and in animals with experimental cirrhosis. The nonosmotic stimulation of arginine vasopressin release from the pituitary has been implicated as an important factor in the abnormal water excretion in patients and animals with cirrhosis. In this study, arginine vasopressin hypothalamic gene expression was studied in cirrhotic rats. Cirrhosis was induced by a combination of phenobarbital treatment in drinking water and weekly intragastric administration of carbon tetrachloride for 13 to 15 wk. Severe cirrhosis was confirmed by morphological analysis and the presence of ascites. Plasma arginine vasopressin was also significantly higher in rats with cirrhosis (control = 1.77 +/- 0.16 and cirrhotic rats = 4.14 +/- 0.62 pg/ml, n = 9, p < 0.002). Hypothalamic arginine vasopressin messenger RNA was also significantly higher in cirrhotic rats (control = 762.1 +/- 132.3 and cirrhotic rats = 1,834.2 +/- 271.9 pg/hypothalamus, n = 9, p < 0.005). Pituitary arginine vasopressin content was significantly lowered in cirrhotic rats (control = 3.69 +/- 0.98 and cirrhotic rats = 1.57 +/- 0.09 micrograms/pituitary, n = 9, p < 0.05). No difference was seen in hypothalamic arginine vasopressin content between the two groups (control = 4.64 +/- 0.34 and cirrhotic rats = 4.23 +/- 0.33 ng/hypothalamus, n = 9, NS). Oxytocin messenger RNA in the hypothalamus was also not significantly different between the two groups (control = 8.61 +/- 0.68 and cirrhotic rats = 9.33 +/- 0.65 unit of density, n = 9, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasopressin gene expression in rats with experimental cirrhosis. 842 35

Over the past several years, the use of 1-deamino-8-D-arginine vasopressin (DDAVP), a synthetic analogue of vasopressin, has been found to be useful in the treatment of patients with abnormal bleeding tendency. This article is a review of inherited and acquired disorders with prolonged bleeding time in which DDAVP is supposed to shorten the bleeding time. DDAVP is established as effective therapy of the abnormal haemostasis in mild or moderate haemophilia A and von Willebrand's disease. Frequently, DDAVP infusions are used to control bleeding in patients with uraemia. Bleeding time is also significantly shortened in patients with liver cirrhosis, although randomized trials of DDAVP therapy of gastrointestinal bleeding in this group of patients are still needed. Shortening or normalization of the bleeding time with DDAVP has also been observed in patients with inherited platelet dysfunctions, acquired disorders of haemostasis and abnormal haemostasis in chronic myeloproliferative diseases. In addition, preoperative treatment with DDAVP seems to reduce blood loss during surgery.
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PMID:[Desmopressin in the treatment of hemorrhagic diathesis]. 854 Jan 36

We determined whether aquaporin of collecting duct (AQP-CD) is involved in pathogenesis of water retention in rats with experimental models of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and liver cirrhosis. SIADH rats were made by administering 1-desamino-8-D-arginine vasopressin (DDAVP) subcutaneously and providing them with a liquid diet. Serum Na levels decreased to < 120 meq/l on day 2, and hyponatremia persisted throughout the rest of observation period. Six hours after the DDAVP infusion, the expression of AQP-CD mRNA significantly increased by 198%, followed by > 144% increases in its expression during the 14-day observation period. On day 7, the increased expression of AQP-CD mRNA was abolished after the administration of an antidiuretic, nonpeptide arginine vasopressin (AVP) antagonist, OPC-31260, which was closely related to a marked diuresis and a prompt normalization of serum Na levels in SIADH rats. Rats were made cirrhotic by injecting a mixture of carbon tetrachloride and olive oil subcutaneously for 3 mo. The expression of AQP-CD mRNA was increased by 164% in the decompensated cirrhotic rats. The blockade of AVP action by OPC-31260 significantly diminished its expression. These results indicate that water channel AQP-CD plays an important role in water retention in pathological states of SIADH and liver cirrhosis.
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PMID:Role of water channel AQP-CD in water retention in SIADH and cirrhotic rats. 859 89

Ascites, a late manifestation of cirrhosis of the liver, causes increased morbidity and mortality. The renin-angiotensin-aldosterone system, the sympathetic nervous system, and arginine vasopressin are responsible for sodium and water retention in patients with cirrhosis. Fluid localizes to the peritoneal cavity mainly as a result of portal hypertension. Recent developments in the understanding of the pathophysiologic mechanisms of ascites include the role of inadequate renal prostaglandin production in the development of the hepatorenal syndrome and the possible role of nitric oxide in the pathogenesis of the renal complications of cirrhosis. The aim of medical therapy is to achieve a negative sodium balance and, consequently, fluid loss. Large-volume paracentesis is safe and effective in the management of tense ascites, but use of diuretic agents should be continued to prevent reaccumulation of ascites. Liver transplantation, transjugular intrahepatic portosystemic shunts, or LeVeen shunts should be considered in selected patients with persistent ascites. In patients with diuretic-resistant or diuretic-refractory ascites, a thorough assessment must be performed to exclude potentially reversible causes. The hepatorenal syndrome has an associated grave prognosis, especially in patients who are not candidates for liver transplantation.
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PMID:Ascites and hepatorenal syndrome: pathophysiology and management. 914 95

Atrial natriuretic peptide (ANP) produced in the heart and prostaglandin E2 (PGE2) synthesised in the kidneys facilitate renal excretion of sodium and water, and thus oppose the actions of angiotensin II, aldosterone, arginine vasopressin (AVP), endothelin, and the renal sympathetic nerves. In the present work we studied the contributions and interactions of these substances in the regulation of blood volume (BV), renal haemodynamics, renal sodium and water handling and blood pressure (BP) in patients with glomerulonephritis and cirrhosis. The aim was through a better understanding of the pathophysiology to improve the treatment of fluid retention in these patients, which occurs as development of the nephrotic syndrome and accumulation of ascites, respectively. Normotensive patients with glomerulonephritis but without the nephrotic syndrome had normal baseline BV values measured as the sum of plasma volume and red cell volume; they responded to BV expansion after infusion of albumin and BV depletion after administration of furosemide with appropriate counterregulatory hormonal changes. However, they tended to hold more fluid within the intravascular phase after both manipulations than did the healthy subjects. The acutely induced increase in BV did not affect the BP, which was likely attributable to the changes in plasma values of angiotensin II and ANP shown. ANP could be expected to be a tool in the management of fluid accumulation in patients with the nephrotic syndrome and cirrhosis. The non-renal effects of high-dose ANP were studied for the first time in dialysis patients without excretory kidney function. A reversible shift of fluid away from the intravascular phase was demonstrated. The BV was maximally reduced 30 min after ANP had been given. The BP was reduced before fluid displacement occurred and to the same extent in patients and healthy subjects. The reduction in the BV was negatively correlated to the reduction in BP. From that study it is inferred that the BP reducing effect of ANP is not mediated by its diuretic effect or ability to displace fluid from the intravascular to the interstitial fluid compartment. As a pharmacological dose of ANP was given, it can only be suggested that endogenous ANP, by altering transcapillary Starling mechanisms, assists in buffering intravascular fluid expansion until renal excretion or dialysis can take place. The same dose of ANP was given to patients with the nephrotic syndrome and cirrhosis. The ability of ANP to increase sodium excretion through inhibition of sodium reabsorption in the distal tubules and to increase the glomerular filtration rate (GFR) was blunted in both patient groups, but the BP was reduced to the same extent as in the healthy controls. Patients with the nephrotic syndrome tended to have a slightly elevated BP. We only studied patients with normal or slightly reduced GFR. They had a normal BV, reduced renal filtration fraction, suppressed aldosterone, increased ANP, but normal plasma values of angiotensin II, endothelin, and AVP, and normal urinary excretion of PGE2. Thus, neither haemodynamic nor hormonal factors can easily explain the spontaneous sodium retention or the resistance to the effects of ANP and furosemide. An interesting finding, not previously reported in nephrotic humans, was the low cyclic guanosine 3'5'-monophosphate (cGMP) in plasma and urine in relation to ANP, both before and after administration of ANP. It is hypothesised that renal resistance to ANP, exaggerated renal cGMP degradation, or preponderance of clearance receptors in nephrotic kidneys may contribute to sodium retention and the low filtration fraction. Elevation of ANP in these patients is connected with increased albuminuria, and probably an increase in intraglomerular capillary pressure. The resistance to furosemide could not be attributed to delayed passage of fluid from the interstitial to the intravascular fluid phase, but is most likely due to renal tubular resistan
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PMID:Regulation of renal sodium and water excretion in the nephrotic syndrome and cirrhosis of the liver. 915 Oct 12

Normalization of the increased vascular nitric oxide (NO) generation with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and ascites were investigated using balance studies. The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L-NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administrated the same volume of vehicle. Two other groups of rats were used as controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7. On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus +1.2 mmol per day, NS). On day 7, CIR-NAME rats had an increase in sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate that normalization of aortic cGMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites.
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PMID:Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites. 942 86

Standard therapy for variceal bleeding includes endoscopic sclerotherapy and esophageal balloon tamponade. In addition, pharmacologic therapies, including arginine vasopressin (AVP), are frequently used in hemodynamically unstable patients or where sclerotherapy has been unsuccessful. A case is described herein of a 30-year-old woman with a history of ethanol abuse, hematemeisis, and biopsy-proven hepatic cirrhosis in which the addition of AVP to an antivariceal regimen of octreotide was associated with a paradoxical episode of hypotension, bradycardia, and hypoxia. Indeed, within 15 minutes after initiation of an AVP infusion, the patient exhibited hypotension with a systolic blood pressure of 80 mmHg, a relative bradycardia to 76 beats per minute, and a desaturation of blood oxygen to 84%. The AVP infusion was discontinued 2 hours later and blood pressure, heart rate, and oxygen saturation rapidly returned to baseline. This temporal correlation between the onset and termination of the physiologic effects and the initiation and discontinuation of the AVP infusion suggests a causal relationship. The paradoxical physiologic effects might reflect cardiac ischemia secondary to vasospasm and/or central suppression of the autonomic nervous system induced by AVP.
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PMID:Paradoxical hypotension and bradycardia after intravenous arginine vasopressin. 954 67

Central to a unifying hypothesis of body fluid regulation is maintenance of arterial circulatory integrity. This may be disturbed by arterial underfilling, either from reduction in cardiac output or by peripheral arterial vasodilation. In cardiac failure (CF), cardiac output falls and the nonosmotic release of arginine vasopressin (AVP) and expression of AVP mRNA in the hypothalamus are stimulated. V2 AVP receptor antagonists correct the impaired water excretion in rats with low-output CF, increase solute free water clearance, correct the hyponatremia in congestive CF patients, and normalize urinary concentrations of the aquaporin-2 (AQP-2) water channels. In conditions associated with peripheral vasodilation, such as cirrhosis, nonosmotic release of AVP also occurs, and AQP-2 gene expression in the rat kidney is up-regulated. In cirrhosis, nitric oxide-mediated vasodilation occurs early prior to water retention. V2 antagonists reverse the latter. In normal pregnancy, plasma AVP is relatively high for the degree of hypoosmolality. Pregnant rats up-regulate AQP-2 in the renal papilla, an effect reversed by V2 receptor antagonists. This supports the hypothesis that AVP is an important mediator of renal water retention in pregnancy. In summary, AVP-mediated water retention through collecting duct AQP-2 water channels is important in both low-output CF and high-output states such as cirrhosis and pregnancy. V2 receptor antagonists reverse the water retention and down-regulate AQP-2 water channels.
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PMID:Pathophysiology of renal fluid retention. 973 67

Coagulopathy in patients with liver disease results from impairments in the clotting and fibrinolytic systems, as well as from reduced number and function of platelets. Parenteral vitamin K replacement corrects coagulopathy related to biliary obstruction, bacterial overgrowth, or malnutrition. Vitamin K is less effective for coagulopathy caused by severe parenchymal liver injury. Transfusion of fresh frozen plasma is the hallmark of treatment of significant coagulopathy in patients with liver disease and active bleeding. Transfusion of fresh frozen plasma also reverses moderate to severe coagulopathy of cirrhosis prior to invasive procedures. Cryoprecipitate is useful for severe coagulopathy with hypofibrinogenemia, especially when avoidance of volume overload is desired. Exchange plasmapheresis is useful in selected patients with coagulopathy due to liver disease, in whom fresh frozen plasma fails to correct coagulopathy or in patients who have coexistent severe fluid overload. Platelet transfusions, pooled or single donor, are useful in thrombocytopenic patients prior to performing invasive procedures or in the presence of significant bleeding, especially when the platelet count is below 50,000/mL. The use of recombinant factor VIIa and thrombopoietin therapy for correction of coagulopathy and thrombocytopenia, respectively, in patients with cirrhosis, is currently under investigation. Therapy with prothrombin complex concentrates, 1-deamino-8-d-arginine vasopressin and antithrombin III concentrates for the management of coagulopathy caused by liver disease can be hazardous and the use of these products is considered investigational at the present time.
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PMID:Coagulopathy of Liver Disease. 1109 2

Cirrhosis is typically associated with a hyperdynamic circulation consisting of low blood pressure, low systemic vascular resistance (SVR), and high cardiac output. We have recently reported that nonspecific inhibition of nitric oxide synthase (NOS) with nitro-L-arginine methyl ester reverses the hyperdynamic circulation in rats with advanced liver cirrhosis induced by carbon tetrachloride (CCl(4)). Although an important role for endothelial NOS (eNOS) is documented in cirrhosis, the role of neuronal NOS (nNOS) has not been investigated. The present study was carried out to specifically investigate the role of nNOS during liver cirrhosis. Specifically, physiological, biochemical, and molecular approaches were employed to evaluate the contribution of nNOS to the cirrhosis-related hyperdynamic circulation in CCl(4)-induced cirrhotic rats with ascites. Cirrhotic animals had a significant increase in water and sodium retention. In the aorta from cirrhotic animals, both nNOS protein expression and cGMP concentration were significantly elevated compared with control. Treatment of cirrhotic rats for 7 days with the specific nNOS inhibitor 7-nitroindazole (7-NI) normalized the low SVR and mean arterial pressure, elevated cardiac index, and reversed the positive sodium balance. Increased plasma arginine vasopressin concentrations in the cirrhotic animals were also repressed with 7-NI in association with diminished water retention. The circulatory changes were associated with a reduction in aortic nNOS expression and cGMP. However, 7-NI treatment did not restore renal function in cirrhotic rats (creatinine clearance: 0.76 +/- 0.03 ml. min(-1). 100 g body wt(-1) in cirrhotic rats vs. 0.79 +/- 0.05 ml. min(-1). 100 g body wt(-1) in cirrhotic rats+7-NI; P NS. ). Taken together, these results indicate that nNOS-derived NO contributes to the development of the hyperdynamic circulation and fluid retention in cirrhosis.
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PMID:Neuronal nitric oxide synthase and systemic vasodilation in rats with cirrhosis. 1109 30

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