Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical course of patients with cirrhosis of the liver is frequently complicated by progressive impairment of renal sodium handling leading to the formation of ascites. The occurrence of ascites is generally accompanied by the activation of several hormones and intrarenal autacoids and a complex derangement of systemic, portal and renal hemodynamics. The earliest "underfilling" theory of sodium retention proposes that ascites formation leads to hypovolemia and secondary sodium retention. According to the "overflow" theory, ascites formation is a secondary event with respect to sodium retention, which occurs as a primary phenomenon in the absence of hypovolemia. A third recently developed theory suggests that peripheral arteriolar vasodilation is the primary event of intravascular underfilling. The major documented site involved in arteriolar vasodilation is the splanchnic circulation. Occurrence of underfilling is not related to a reduction of plasma volume but to the enlargement of the vascular compartment. Vascular underfilling triggers a series of hemodynamic and hormonal compensatory events such as an increase in cardiac output and plasma volume, activation of the renin-angiotensin-aldosterone and sympathetic nervous system and non-osmotic hypersecretion of antidiuretic hormone and sodium retention, all of which aim at refilling the vascular compartment. In patients with compensated cirrhosis, i.e. without ascites, compensatory events maintain blood volume despite vascular underfilling, and so these patients do not develop ascites. In patients with decompensated cirrhosis, vascular underfilling due to arterial vasodilation, together with a reduced oncotic pressure and a severe degree of portal hypertension, favours the development of ascites. Underfilling of the arterial circulation is at its maximum in functional renal failure and the hepatorenal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ascites in liver diseases. 174 50

Renal sodium and water retention and plasma volume expansion have been shown to precede ascites formation in experimental cirrhosis. The classical "underfilling" theory, in which ascites formation causes hypovolemia and initiates secondary renal sodium and water retention, thus seems unlikely. While the occurrence of primary renal sodium and water retention and plasma volume expansion prior to ascites formation favors the "overflow" hypothesis, the stimulation of the renin-angiotensin-aldosterone system, vasopressin release and sympathetic nervous system associated with cirrhosis is not consonant with primary volume expansion. In this present article, the "Peripheral Arterial Vasodilation Hypothesis" is proposed as the initiator of sodium and water retention in cirrhosis. Peripheral arterial vasodilation is one of the earliest observations in the cirrhotic patient and experimental animals with cirrhosis. Arterial vasodilators and arteriovenous fistula are other examples in which renal sodium and water retention occur secondary to a decreased filling of the arterial vascular tree. An increase in cardiac output and hormonal stimulation are common features of cirrhosis, arteriovenous fistula and drug-induced peripheral arterial vasodilation. However, a predilection for the retained sodium and water to transudate into the abdominal cavity occurs with cirrhosis because of the presence of portal hypertension. The Peripheral Arterial Vasodilation Hypothesis also explains the continuum from compensated to decompensated cirrhosis to the hepatorenal syndrome.
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PMID:Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. 270 44

A 47-year-old patient with severe decompensated alcoholic liver disease developed a progressive deterioration of her renal function (serum creatinine 4.0 mg/dL) with a renal failure index (RFI: UNa/U/PCr) consistently less than 1.0. In the absence of other causes of renal failure, these values supported the diagnosis of hepatorenal syndrome (HRS). A five-hour head-out water immersion (HWI) in a sitting position was carried out to increase the patient's "effective" blood volume (EBV) in an attempt to reverse the HRS. Hemodynamic monitoring (Swan-Ganz) was performed during the entire HWI procedure. Cardiac index increased by 64% during HWI (2.57 to 4.22 L/min/m2). Stroke volume index doubled (32.9 to 65.0 mL/m2) and systemic vascular resistance decreased by 48% (1426 to 754 dyne sec/cm). Increases in right atrium (RA) pressure (7.5 to 17.5 mm Hg) and pulmonary wedge (PW) capillary pressure (7.5 to 16.3 mm Hg) also occurred. Hemoglobin, hematocrit, and plasma protein concentrations decreased by 18% during HWI. Only a modest improvement in creatinine, urea, inulin, and para-aminohippurate (PAH) clearances was observed during HWI, and the RFI remained below 1.0. Plasma levels of antidiuretic hormone (ADH), aldosterone, and renin activity decreased during HWI. The patient's renal function progressively deteriorated over the next 15 days, but tubular function, as assessed by an RFI less than 1.0, was still intact seven days after our study. Our results indicate that a considerable increase in effective blood volume does not restore renal function in HRS.
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PMID:Effect of head-out water immersion on hepatorenal syndrome. 669 41

Hepatorenal syndrome is a life-threatening complication of severe liver disease. It is generally accepted that the syndrome is the final stage of complex hemodynamic derangements associated with portal hypertension, ie, peripheral arterial vasodilation, effective hypovolemia, and hyperkinetic status. In spite of reduced systemic resistances, intrarenal vascular resistances are increased. This is probably the consequence of the activation of systemic vasoactive factors, such as the renin-angiotensin system, the sympathetic nervous system, and vasopressin aimed at restoring arterial filling pressure. Recently, it has been shown that intrarenal vasoconstrictors, such as leukotrienes and endothelins, are activated with the progression of liver disease. The renal vasoconstriction is counterbalanced by the intrarenal hyperproduction of vasodilating prostaglandins and kallikreins. When this balance is lost, for whatever mechanism, the renal vascular resistances dramatically increase and the hepatorenal syndrome develops. In spite of increased knowledge about pathogenesis, the treatment of hepatorenal syndrome remains unresolved. Low-dose dopamine or ornipressin are currently employed in many liver units to avoid further deterioration of renal function in patients with severe liver disease who are waiting for liver transplantation that remains, at present, the only effective treatment for hepatorenal syndrome.
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PMID:Hepatorenal syndrome. New perspectives in pathogenesis and treatment. 835 80

In patients with advanced liver disease, decreases in renal blood flow, glomerular filtration rate, and urinary output are frequently observed. The deterioration in renal function is usually not due to a unique cause but is the result of the concerted action of several mechanisms operating in parallel; decreased plasma protein formation and increased intrahepatic vascular resistance lead to sequestration of blood volume, favoring hypovolemia and reduction in cardiac output. At the same time enhanced formation of nitroxide leads to peripheral vasodilation; bacterial endotoxin escaping clearance by the diseased liver stimulates the expression of a long-acting nitroxide synthase. Furthermore, vasodilating intestinal mediators such as substance P escape inactivation by the liver. In the face of peripheral vasodilation the maintenance of blood pressure requires an increase in cardiac output, which is achieved by activation of sympathetic nervous tone, renal vasoconstriction, enhanced release of renin, angiotensin, aldosterone, and antidiuretic hormone, leading to renal retention of sodium and water. Renal vasoconstriction is opposed by vasodilatatory prostaglandins, and renal failure may be triggered by inhibition of prostaglandin formation. On the other hand, vasoconstrictive eicosanoids, such as thromboxane B2 and leukotriene E2, which escape hepatic inactivation, may contribute to renal vasoconstriction. Beyond these mechanisms disturbed hepatic regulation of renal function may participate in the generation of hepatorenal syndrome. The liver regulates renal function via both a hepatorenal reflex decreasing renal blood flow and a hypothetical liver-borne diuretic factor increasing renal blood flow. Both enhanced hepatorenal reflex activity and decreased formation of the liver-borne diuretic factor could participate in the pathogenesis of hepatorenal syndrome.
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PMID:New clues to the pathophysiology of hepatorenal failure. 846 32

In patients with hepatorenal syndrome (HRS), 4-hr administration of a vasopressin analog has recently been shown to benefit renal blood flow and renal function. However, long-term effects and tolerance of this treatment have not been reported. We report a case of HRS that was controlled by the vasopressin analog, terlipressin. Because HRS repeatedly relapsed when treatment was discontinued, terlipressin, 2 mg/day was administered for 67 days, until liver transplantation could be performed in a patient with normal renal function. Except for limited cutaneous necrosis at an injection point, prolonged treatment with this vasopressin analog was well tolerated.
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PMID:Hepatorenal syndrome. Long-term treatment with terlipressin as a bridge to liver transplantation. 865 33

Ultrasonography detects ascites easily even in trace amounts. 80% of the cases are caused by hepatic disease, in the remaining 20% cancer, inflammation, pancreatic, renal, or cardiac disease can be found. The underlying disease should be investigated by few inexpensive laboratory test from serum, urine and ascites and by abdominal sonography. Hepatic ascites is caused by portal hypertension and disturbances of humoral factors. Sodium retention, peripheral, vasodilation, hyperdynamic circulation and progressive renal vasoconstriction lead to a stepwise deterioration of patients condition. Treatment with diuretics (furosemide, torsemide, or xipamide and spironolactone) and sodium-restriction (< 60 mval per day) control 85-90% of the cases with hepatic ascites. If this regimen fails, non-compliance, spontaneous bacterial peritonitis, hyponatremia or additional complications such as renal failure, Budd-Chiari syndrome or tumor should be considered. Ten to 15% of the patients develop refractory ascites and finally hepatorenal syndrome and have a poor prognosis. Early liver transplantation should be considered. Large volume paracentesis with albumin substitution is a therapeutic option in these patients. The transjugular intrahepatic portosystemic stent-shunt (TIPS) may be superior for patients with concurrent esophageal varices or hepatorenal syndrome. If TIPS is considered the patient should be referred to an experienced center. The peritoneo-venous shunt is restricted to rare indications. In the future, new drugs such as antagonists of endothelins or of the antidiuretic hormone may offer new therapeutic options.
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PMID:[Current ascites therapy]. 906 26

The pathogenesis of renal sodium and water retention in cirrhosis involves extrarenal mechanisms because when kidneys from cirrhotic patients are transplanted into persons with normal livers, renal sodium and water retention no longer occurs. Cirrhosis is accompanied by portal hypertension, which leads to a hyperdynamic circulatory state. The Peripheral Arterial Vasodilation Hypothesis incriminates a relative underfilling of the arterial vascular compartment, which leads to the same neurohumoral responses that occurs in low cardiac output. Activation of the renain-angiotensin-aldosterone axis and the sympathetic system as well as non-osmotic release of vasopressin are well documented in cirrhosis. This sequence of events results in renal water and sodium retention, failure to escape from the sodium-retaining effect of aldosterone, and renal resistance to atrial natriuretic peptide. Dilutional hyponatremia is the strongest predictor of the occurrence of hepatorenal syndrome. The pathogenesis of the peripheral arterial vasodilation is not completely elucidated, but there is evidence for a major role of nitric oxide (NO). Increased vascular NO production has been demonstrated in cirrhosis. In the rat model of cirrhosis, normalization of vascular NO production with a NOS inhibitor corrects the hyperdynamic circulation, improves sodium and water excretion, and decreases neurohumoral activation. This insight into the mechanism(s) of the peripheral arterial vasodilation in cirrhosis should provide new tools in the treatment of edema and ascites, a major cause of morbidity and mortality in cirrhosis.
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PMID:Pathogenesis of water and sodium retention in cirrhosis. 918 4

The effects of the acute administration of arterial vasoconstrictors on renal plasma flow (RPF) and urinary sodium excretion (UNaV) in cirrhotic patients with ascites with or without hepatorenal syndrome (HRS) are still controversial. As a consequence, vasoconstrictors are not actually used in the treatment of renal sodium retention or HRS in these patients, regardless of the several lines of evidence suggesting that these renal functional abnormalities are related to a marked arterial vasodilation. The lack of an orally available effective arterial vasoconstrictor probably represents a further reason for this omission. Consequently, the present study was made to evaluate the acute effects of the oral administration of midodrine, an orally available -mimetic drug, on systemic and renal hemodynamics and on UNaV in cirrhotic patients with ascites. Mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), systemic vascular resistance (SVR), left forearm blood flow (LFBF), left leg blood flow (LLBF), RPF, glomerular filtration rate (GFR), UNaV, plasma renin activity (PRA), plasma concentration of antidiuretic hormone (ADH), and the serum levels of nitrite and nitrate (NOx) were evaluated in 25 cirrhotic patients with ascites (17 without HRS and 8 with type 2 HRS) before and during the 6 hours following the oral administration of 15 mg of midodrine. During the first 3 hours after the drug administration, a significant increase in MAP (89.6 +/- 1.7 vs. 81.80 +/- 1.3 mm Hg; P < .0001) and SVR (1, 313.9 +/- 44.4 vs. 1,121.2 +/- 60.1 dyn . sec . cm-5; P < .0001) accompanied by a decrease in HR (69 +/- 2 vs. 77 +/- 3 bpm; P < .005) and CI (2,932.7 +/- 131.4 vs. 3,152.5 +/- 131.4 mL . min-1 . m2 BSA; P < .0025) was observed in patients without HRS. No change was observed in LFBF and LLBF. The improvement in systemic hemodynamics, which was also maintained during the the 3- to 6-hour period after midodrine administration, was accompanied by a significant increase in RPF (541.5 +/- 43.1 vs. 385.7 +/- 39.9 mL . min-1; P < .005), GFR (93.1 +/- 6.5 vs. 77.0 +/- 6.7 mL . min-1; P < .025), and UNaV (92.7 +/- 16.4 vs. 72.2 +/- 10.7 microEq . min-1; P < .025). In addition, a decrease in PRA (5.33 +/- 1.47 vs. 7.74 +/- 2.17 ng . mL-1 . h; P < .05), ADH (1.4 +/- 0.2 vs. 1.7 +/- 0.2 pg . mL-1; P < .05), and NOx (33.4 +/- 5.0 vs. 49.3 +/- 7.3 micromol-1; P < .05) was found. In patients with HRS, the effects of the drug on the systemic hemodynamics was smaller and shorter. Accordingly, regardless of a significant decrease in PRA (15.87 +/- 3.70 vs. 20.70 +/- 4.82 ng . mL-1 . h; P < .0025) in patients with HRS, no significant improvement was observed in RPF, GFR, or UNaV. In conclusion, the acute oral administration of midodrine is associated with a significant improvement in systemic hemodynamics in nonazotemic cirrhotic patients with ascites. As a result, renal perfusion and UNaV also improve in these patients. By contrast, midodrine only slightly improves systemic hemodynamics in patients with type 2 HRS, with no effect on renal hemodynamics and renal function.
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PMID:Acute effects of the oral administration of midodrine, an alpha-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites. 975 29

A 47-year-old male patient with alcoholic cirrhosis Child-Pugh grade C was admitted to our center for evaluation of liver transplantation. Serum creatinine had increased from 1.6 to 4.3 mg/100 ml within the previous two weeks, creatinine clearance was 12 ml/min, and urinary sodium 12 mmol/24 h. The diagnosis of HRS type I was established. Diuretic treatment was discontinued. Following albumin infusion, central venous pressure was increased to above 10 cm H2O and dopamine (2 micrograms/kg/min) infusion was started. However, renal function did not improve. An i.v. infusion of ornipressin (POR8, Sandoz; 6 IU/h) was started and dopamine infusion continued. During a four-hour interval, urinary volume and sodium excretion doubled. Therefore treatment was continued for three weeks. After 22 days, renal function had normalized (creatinine 1.2 mg/100 ml, creatinine clearance 65 ml/min, urinary sodium 62 mmol/24 h) and diuretic therapy was resumed. No adverse effects were observed. Ornipressin/dopamine infusion was discontinued and renal function remained normal. Three weeks later, the patient underwent liver transplantation with normal renal function. Ornipressin infusion had no effect on circulating endothelin, but decreased the activation of the renin-aldosterone system and of the sympathetic activity. So far, no noninvasive therapy of hepatorenal syndrome has been established. This is the first report of successful medical treatment of HRS type I with a three-week infusion of the vasopressin-l-receptor agonist ornipressin.
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PMID:[Successful conservative therapy of hepatorenal syndrome with vasopressin-1-receptor antagonist ornipressin]. 1002 57


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