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)

An oral water load of 20 ml kg-1 body weight was given to 11 patients with early hepatic cirrhosis and to 16 healthy control subjects. Urinary output (V), free water clearance (CH2O), urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), and plasma concentration of arginine vasopressin (AVP) were determined before and during the first 4 h after loading. During basal conditions, PGE2 excretion was the same in patients (75 pg min-1, median, range 15-569) and controls (78 pg min-1, range 22-262), but during the first hour after water loading, PGE2 increased to a significantly higher level in cirrhotic patients (423 pg min-1, median) than in control subjects (162 pg min-1) (P less than 0.05). No difference in PGF2 alpha excretion was found between the two groups. Urinary output and CH2O were significantly lower after water loading in patients than in controls. Arginine vasopressin before water loading did not differ between patients and control subjects, but after loading it was unchanged in the patients, whereas a significant reduction (1.9 to 1.4 pmol l-1, P less than 0.01) was found in the control subjects. In controls, but not in patients, PGE2 was significantly positively correlated to V and CH2O, and negatively correlated to AVP after water loading. Thus, renal PGE2 excretion is increased and CH2O is decreased after water loading in patients with early hepatic cirrhosis, and a disturbed relationship seems to exist between PGE2 on the one hand, and AVP and renal water excretion, on the other, in these patients after water loading.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disturbed relationship between urinary prostaglandin E2 excretion, plasma arginine vasopressin and renal water excretion after oral water loading in early hepatic cirrhosis. 313 26

Arginine vasopressin (AVP) is a neuropeptide hormone that plays an important role in circulatory and sodium homeostasis, and regulating serum osmolality. Several clinical conditions have been associated with inappropriately elevated levels of AVP including heart failure, cirrhosis of the liver and the syndrome of inappropriate secretion of antidiuretic hormone. Three receptor subtypes that mediate the actions of AVP have been identified (V(1A), V(2) and V(1B)). Activation of V(1A) receptors located in vascular smooth muscle cells and the myocardium results in vasoconstriction and increased afterload and hypertrophy. The V(2) receptors located primarily in the collecting tubules mediate free water absorption. The V(1B) receptors are located in the anterior pituitary and mediate adrenocorticotropin hormone release. The cardiovascular and renal effects of AVP are mediated primarily by V(1A) and V(2) receptors. Antagonism of V(1A) receptors results in vasodilatation and antagonism of V(2) receptors resulting in aquaresis, an electrolyte-sparing water excretion. Several non-peptide AVP antagonists (vasopressin receptor antagonists [VRAs]) also termed 'vaptans' have been developed and are vigorously being studied primarily for treating conditions characterised by hyponatraemia and fluid overload. Conivaptan is a combined V(1A)/V(2)-receptor antagonist that induces diuresis as well as haemodynamic improvement. It has been shown in clinical trials to correct euvolaemic and hypervolaemic hyponatraemia, and has been approved by the US FDA for the treatment of euvolaemic hyponatraemia as an intravenous infusion. Tolvaptan, a selective V(2)-receptor antagonist, has undergone extensive clinical studies in the treatment of hyponatraemia and heart failure. It has been shown to effectively decrease fluid in volume overloaded patients with heart failure and to correct hyponatraemia. A large outcome study (n = 4133 patients) will define its role in the management of heart failure. Lixivaptan and satavaptan (SR-121463) are other selective V(2)-receptor antagonists being evaluated for the treatment of hyponatraemia. In addition, a potential role for the vaptans in attenuating polyuria in nephrogenic diabetes insipidus and cyst development in polycystic kidney disease is being explored. Ongoing clinical trials should further define the scope of the potential therapeutic role of VRAs.
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PMID:Therapeutic potential of vasopressin receptor antagonists. 1742 3

Hyponatremia, which is often due to dysregulation of arginine vasopressin, occurs frequently in hospitalized patients and is associated with increased morbidity and mortality. Nonosmotic secretion of arginine vasopressin is central to the pathophysiology of hyponatremia in patients with euvolemic hyponatremia (due to, for example, the syndrome of inappropriate secretion of antidiuretic hormone) and those with hypervolemic hyponatremia secondary to congestive heart failure or cirrhosis with ascites. Arginine vasopressin-receptor antagonists, a novel class of agents that block the action of arginine vasopressin on V2 receptors in the renal collecting ducts, may provide specific correction of sodium and water imbalance in hyponatremia by promoting free water clearance while sparing electrolytes (aquaresis). Arginine vasopressin antagonism would treat hyponatremia directly, as opposed to other therapies that do not address the effects of arginine vasopressin dysregulation directly.
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PMID:Vasopressin dysregulation and hyponatremia in hospitalized patients. 1771 57

Arginine vasopressin is a naturally occurring peptide with established physiological functions acting as a vasoconstrictor through V1 receptors or an aquagenic agent allowing free water retention through V2 receptors in the kidney. Portal haemodynamic changes of chronic liver disease are responsible for the lethal consequences of cirrhosis--bleeding oesophageal varices and hepatorenal syndrome. Increasing hepatic vascular resistance to blood flow coupled with central hypovolaemia and a hyperdynamic circulation driven by changes in nitric oxide responsiveness disturbs the normal circulatory physiology raising portal pressure. Vasopressin and its analogues are potent vasoconstrictors and can be utilised in the management of the complications of cirrhosis. Hyponatraemia is common in end stage liver disease due in part to sodium retention and a decreased free water clearance. Diuretic therapy often leads to a worsening of the sodium status and have little true effect on improving free water clearance. Recently a new class of drugs, V2 receptor antagonists, have been evaluated in chronic liver disease whereby increasing free water clearance they may reduce ascitic fluid development. This review addresses the pharmacology of both vasopressin agonists and antagonists, their clinical application and future potential roles in managing patients with acute on chronic liver failure.
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PMID:Vasopressin in liver disease--should we turn on or off? 1878 2

Arginine vasopressin, also known as antidiuretic hormone, is a neuropeptide that functions in the maintenance of body water homeostasis. Inappropriate secretion of vasopressin has been implicated in the pathophysiology of multiple diseases, including polycystic kidney disease, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and the hyponatremia commonly associated with cirrhosis and congestive heart failure. Vasopressin receptor antagonists are novel agents that block the physiologic actions of vasopressin. Lixivaptan is a vasopressin receptor antagonist with high V2 receptor affinity and is now undergoing Phase III clinical trials. Studies so far have demonstrated that lixivaptan is efficacious in the correction of hyponatremia in SIADH, heart failure and liver cirrhosis with ascites, and few adverse effects have been noted. Thus, lixivaptan remains a promising therapeutic modality for the treatment of multiple diseases and prevention of the associated morbidity and mortality associated with hyponatremia.
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PMID:Lixivaptan: a novel vasopressin receptor antagonist. 1937 24

Lixivaptan (VPA-985), being developed by Biogen Idec and Cardiokine, under license from Wyeth (now part of Pfizer), is a non-peptide, selective vasopressin V2 receptor antagonist for the potential oral treatment of hyponatremia associated with heart failure. Arginine vasopressin, the native V2 receptor ligand, stimulates water reabsorption via activation of V2 receptors that are expressed in the collecting ducts of the kidney. In preclinical studies, lixivaptan displayed competitive antagonist activity at V2 receptors in vitro, and increased urine volume and decreased urine osmolality in rats and dogs. The therapeutic benefits of lixivaptan are being evaluated in patients with conditions that are associated with water excess and hyponatremia. Phase II clinical trials in patients with congestive heart failure, liver cirrhosis with ascites or syndrome of inappropriate antidiuretic hormone have demonstrated that, unlike traditional diuretics, lixivaptan increases water clearance without affecting renal sodium excretion or activating the neurohormonal system. Administration of lixivaptan in combination with the diuretic furosemide has been tested in rats as well as in trials in healthy volunteers, in which the two agents were well tolerated. Ongoing phase III trials will determine the role of lixivaptan in the management of hyponatremia, especially when associated with heart failure.
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PMID:Lixivaptan, a non-peptide vasopressin V2 receptor antagonist for the potential oral treatment of hyponatremia. 2104 26

Arginine vasopressin (AVP) is the major physiological regulator of renal water excretion and blood volume. The AVP pathways of V(1a)R-mediated vasoconstriction and V(2)R-induced water retention represent a potentially attractive target of therapy for edematous diseases. Experimental and clinical evidence suggests beneficial effects of AVP receptor antagonists by increasing free water excretion and serum sodium levels. This review provides an update on the therapeutic implication of newly developed AVP receptor antagonists in respective disorders, such as chronic heart failure, liver cirrhosis and syndrome of inappropriate antidiuretic hormone secretion.
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PMID:Arginine vasopressin (AVP) and treatment with arginine vasopressin receptor antagonists (vaptans) in congestive heart failure, liver cirrhosis and syndrome of inappropriate antidiuretic hormone secretion (SIADH). 2132 10

Arginine vasopressin (AVP) plays an important role in water and sodium homeostasis. It acts via three receptor subtypes-V1a, V1b, and V2-distributed widely throughout the body. Vaptans are nonpeptide vasopressin receptor antagonists (VRA). By property of aquaresis, VRAs offer a novel therapy of water retention. Conivaptan is a V1a/V2 nonselective VRA approved for euvolemic and hypervolemic hyponatremia. Tolvaptan is the first oral VRA. Other potential uses of this new class of drugs include congestive heart failure (CHF), cirrhosis of liver, syndrome of inappropriate secretion of antidiuretic hormone, polycystic kidney disease, and so on. These novel drugs score over diuretics as they are not associated with electrolyte abnormalities. Though much remains to be elucidated before the VRAs are applied clinically, the future holds much promise.
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PMID:Vaptans: A new option in the management of hyponatremia. 2377 17