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)

A working formulation for the role of ANF in the sodium retention of cirrhosis is summarized in Figure 4. Sodium retention is initiated early in cirrhosis, either as a result of hepatic venous outflow block or of primary vasodilation. The consequent intravascular volume expansion causes increases in ANF levels. At this stage of disease, the rise in ANF level is sufficient to counterbalance the antinatriuretic influences. However, this occurs at the expense of an expanded intravascular volume with the potential for overflow ascites. With progression of disease, disruption of intrasinusoidal Starling forces and loss of volume from the vascular compartment into the peritoneal compartment occur. This underfilling of the circulation may attenuate further increases in plasma ANF and promotes the activation of antinatriuretic factors. At this later stage of disease, elevated levels of ANF are insufficient to counterbalance antinatriuretic influences. Thus the role of ANF in cirrhosis is primarily beneficial in that it successfully attenuates the antinatriuretic forces in the compensated stage. Raised ANF levels have two potential deleterious effects. First, ANF may exacerbate arterial vasodilation, leading to further sodium retention. The primacy of vasodilatation has been proposed as an alternate formulation to the overflow and underfill hypotheses. Second, Epstein et al. found higher basal ANF levels in cirrhotic patients with edema than in those patients without edema. ANF is known to reduce plasma volume in anephric animals and to increase the ultrafiltration coefficients of isolated capillaries. Therefore it is conceivable that in the clinical setting in which antinatriuretic factors limit the renal responsiveness to ANF but in which ANF levels are elevated (i.e., cirrhosis, congestive heart failure, primary kidney disease), ANF itself may contribute to edema formation at the level of the peripheral microcirculation. In general, ANF likely has no primary role in the sodium retention in cirrhosis. In early compensated cirrhosis, ANF may maintain sodium homeostasis despite the presence of mild antinatriuretic factors. In late ascitic cirrhosis renal resistance to ANF develops, rendering it ineffective.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Atrial natriuretic factor and liver disease. 844 24

The aim of the present study was to investigate the relationship between ET plasma concentrations and other hormonal systems in acute volume regulation of patients with cirrhosis. Ten healthy controls and 10 cirrhotic patients, five without and five with ascites were studied after 1 h in a sitting posture and subsequently subjected to 1 h head-out water immersion. Blood was collected for determinations of ET-1, ET-3, ANF, aldosterone, renin activity and noradrenaline. In addition, in 10 patients with compensated cirrhosis the effect of loop diuretics on ET-3, aldosterone and renin was studied. ETs in cirrhosis were significantly (P < 0.01) higher than in controls both before (ET-1, 19.6 +/- 1.3 pgmL-1 vs. 11.8 +/- 0.4 pgmL-1; ET-3, 18.5 +/- 1.4 pgmL-1 vs. 9.5 +/- 0.5 pgmL-1) and after water immersion (ET-1, 18.6 +/- 1.2 pgmL-1 vs. 12.4 +/- 0.3 pgmL-1; ET-3, 18.7 +/- 1.7 pgmL-1 vs. 10.0 +/- 0.5 pgmL-1). In cirrhotic patients, basal and immersion concentrations of ET-1 were significantly correlated to noradrenaline plasma concentrations (r = 0.79, P < 0.05). ET-3 plasma concentrations in cirrhosis were correlated to renin activity (r = 0.65, P < 0.05). Furthermore, ET-3 in cirrhosis was inversely correlated to systolic and mean arterial blood pressure (r = -0.55, P < 0.01 and r = -0.50, P < 0.05; respectively). To investigate the effect of hypovolaemia in compensated cirrhosis, 10 patients without ascites were studied before and after treatment with loop diuretics. In compensated cirrhosis ET-3 was significantly increased 6h after oral diuretic treatment (17.9 +/- 1.0 pgmL-1 vs. 15.5 +/- 0.4 pgmL-1, P < 0.001). The presented data demonstrate relations of endothelins, particularly of ET-3 to neurohumoral systems in patients with cirrhosis of the liver.
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PMID:Relation of endothelins to volume regulating neurohumoral systems in patients with cirrhosis of the liver. 871 27

VPA-985 is an orally active, competitive vasopressin V(2) receptor antagonist that in normal human beings increases water excretion without affecting solute excretion. Whether solute excretion is affected in patients with hyponatremia resulting from inappropriate secretion of antidiuretic hormone (SIADH) or from cirrhosis treated with VPA-985 is unknown. Six hyponatremic patients with SIADH and 5 hyponatremic patients with cirrhosis with ascitis (CWAs) were treated with 50 or 100 mg VPA-985 twice daily. Evolution of creatinine, urea, uric acid, sodium, potassium, and osmotic clearance were determined. Volume hormones (plasma renin [PR], aldosterone, antidiuretic hormone [ADH], atrial natriuretic factor [ANF]) were also determined before and after treatment. In patients with SIADH, serum sodium concentration (SNa) was generally corrected in 1 day (SNa: 126 +/- 4.5 mmol/L at t = 0 hours and 133 +/- 5.6 mmol/L at t = 24 hours) and associated with a decrease in sodium excretion (from 82 +/- 22 mmol/24 hours to 45 +/- 21 mmol/24 hours; P < 0.05) without modification in potassium excretion. Despite an increase in diuresis (from 0.84 +/- 0.2 ml/min to 1.46 +/- 0.4 ml/min) urea and uric acid clearances decreased. Urine osmolality decreased from 414 +/- 148 mOsm/kg H(2)O to 209 +/- 55 mOsm/kg H(2)O. Volume hormones did not change. In the CWAs the rise of SNa was more progressive (SNa: 126 +/- 2.8 mmol/L at t = H0 to 133 +/- 4.9 mmol/L at t = 48 hours) and parallel to an augmentation in sodium excretion (from 23 +/- 18 mmol/24 hours to 65 6 60 mmol/24 hours the second day of VPA administration). The higher sodium excretion was also connected with a progression in potassium excretion (from 22 6 7 mmol/24 hours to 36 +/- 18 mmol/24 hours). The increase in diuresis under VPA from 0.42 +/- 0.2 mL/min to 1.7 +/- 0.9 mL/min resulted in a higher urea clearance. Urine osmolality decreased from 509 +/- 142 mOsm/kg H(2)O before VPA to 194 +/- 106 mOsm/kg H(2)O after VPA. ADH increased in CWAs treated with VPA, from 1.9 +/- 1.2 pg/mL to 5.3 +/- 2.8 pg/mL (P <.05) while other volume hormones did not change. VPA-985 is a highly effective drug in the short-term management of hyponatremic patients with SIADH or CWAs. SNa correction is associated with urinary sodium retention in SIADH, whereas in CWAs a mild increase in sodium excretion is observed.
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PMID:Difference in solute excretion during correction of hyponatremic patients with cirrhosis or syndrome of inappropriate secretion of antidiuretic hormone by oral vasopressin V2 receptor antagonist VPA-985. 1175 87

Portal hypertension induces neuroendocrine activation and a hyperkinetic circulation state. This study investigated the consequences of portal hypertension on heart structure and function. Intrahepatic portal hypertension was induced in male Sprague-Dawley rats by chronic bile duct ligation (CBDL). Six weeks later, CBDL rats showed higher plasma angiotensin-II and endothelin-1 (P <.01), 56% reduction in peripheral resistance and 73% reduction in pulmonary resistance (P <.01), 87% increase in cardiac index and 30% increase in heart weight (P <.01), and increased myocardial nitric oxide (NO) synthesis. In CBDL rats, macroscopic analysis demonstrated a 30% (P <.01) increase in cross-sectional area of the left ventricular (LV) wall without changes in the LV cavity or in the right ventricle (RV). Histomorphometric analysis revealed increased cell width (12%, P <.01) of cardiomyocytes from the LV of CBDL rats, but no differences in myocardial collagen content. Myocytes isolated from the LV were wider (12%) and longer (8%) than right ventricular myocytes (P <.01) in CBDL rats but not in controls. CBDL rats showed an increased expression of ANF and CK-B genes (P <.01). Isolated perfused CBDL hearts showed pressure/end-diastolic pressure curves and response to isoproterenol identical to sham hearts, although generated wall tension was reduced because of the increased wall thickness. Coronary resistance was markedly reduced. This reduction was abolished by inhibition of NO synthesis with N-nitro-L-arginine. Expression of eNOS was increased in CBDL hearts. In conclusion, portal hypertension associated to biliary cirrhosis induces marked LV hypertrophy and increased myocardial NO synthesis without detectable fibrosis or functional impairment. This observation could be relevant to patients with cirrhosis.
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PMID:Left ventricular hypertrophy in rats with biliary cirrhosis. 1293 85


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