Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Nitric oxide (NO) is postulated to play a role in the pathogenesis of arterial vasodilation in chronic portal hypertension. This present study investigates the relationship between systemic hemodynamics and the vascular production of NO, as estimated by measuring cyclic guanosine monophosphate (cGMP) in aortic tissue in two models of chronic portal hypertension in the rat: the partial portal vein ligation (PVL) model and CCl4-induced cirrhosis. NOS was also examined by Western blotting in aortic and mesenteric vessels. Sham-operated rats and rats given phenobarbital were used as controls. PVL rats and rats with cirrhosis and ascites showed a typical pattern of a hyperdynamic circulatory state, when compared with their respective controls: mean arterial pressure; PVL: 113 +/- 2 versus 124 +/- 2, P < .01 and cirrhotics: 103 +/- 5 versus 130 +/- 4 mm Hg, P < .01. Cardiac index; PVL: 32 +/- 2 versus 26 +/- 1, P < .01 and cirrhotics: 51 +/- 3 versus 30 +/- 1 mL . min-1 . 100 gm-1, P < .0001. Systemic vascular resistance; PVL: 3.7 +/- 0.1 versus 4.9 +/- 0.2, P < .01 and cirrhotics: 2.1 +/- 0.2 versus 4.4 +/- 0.2 mm Hg . min-1 100 g-1, P < .0001. Aortic cGMP was markedly increased in cirrhotic rats with ascites (728 +/- 83 fmol/ mg protein) as compared with phenobarbital-treated controls (244 +/- 31 fmol/mg, P < .001). This increase was abolished by chronic administration of N(omega)-nitro-L-arginine methyl ester. By contrast, PVL rats had an aortic cGMP concentration similar to sham-operated controls (282 +/- 16 fmol/mg vs. 274 +/- 33 fmol/mg, P = not significant) and significantly lower than that found in cirrhotic rats with ascites. Expression of cirrhotic aortic endothelial nitric oxide synthase (eNOS) was increased but PVL aortic eNOS did not differ from that of controls, whereas the mesenteric eNOS was increased in both PVL and cirrhotic rats as compared with the controls. These results suggest that vascular NO production is higher in cirrhotic rats than in PVL rats. This increased production may contribute to the more marked abnormalities in systemic hemodynamics seen in experimental cirrhosis as compared with PVL.
...
PMID:Comparison of vascular nitric oxide production and systemic hemodynamics in cirrhosis versus prehepatic portal hypertension in rats. 885 3

Cyclic guanosine monophosphate (cGMP) has been proposed to mediate peripheral arterial vasodilation in liver cirrhosis. Nitric oxide and natriuretic peptides are the main signals for cGMP generation. Variation in urinary cGMP excretion parallels changes in plasma cGMP levels. Our aim was to determine urinary excretion of cGMP (UcGMPV) and to investigate its relationship to systemic hemodynamics, neurohumoral activity and renal sodium excretion in cirrhosis. Urinary excretion of cGMP was measured in 19 healthy subjects and 20 patients with alcoholic cirrhosis. Systemic hemodynamic parameters, blood volume (BV), plasma atrial natriuretic factor (ANF), and the endothelium-dependent vasodilator substance P (SP) were determined in all patients and in five healthy subjects. Urinary cGMPV was higher in the group of patients (736 pg/min; 50-3229 pg/min) than in controls (126 pg/min; 0-1657 pg/min) (P < 0.01). In addition, UcGMPV inversely correlated with the systemic vascular resistance and directly with cardiac output, blood volume, SP, ANF, and Pugh's score. By Cox regression analysis, only systemic vascular resistance remained inversely associated with UcGMPV. In conclusion, urinary cGMP excretion is increased in cirrhosis. It is suggested that increased cGMP generation may be related to the hyperkinetic circulation in human cirrhosis.
...
PMID:Enhanced urinary excretion of cGMP in liver cirrhosis. Relationship to hemodynamic changes, neurohormonal activation, and urinary sodium excretion. 924 39

To investigate the role of nitric oxide (NO) with respect to kidney function and liver cirrhosis, we evaluated renal function, as well as cyclic guanosine monophosphate (cGMP) and NOx (nitrite/nitrate [NO3-/NO2-]) as indirect markers of NO formation in plasma and urine at rest and during amino acid (aa)-induced glomerular hyperfiltration in patients with Child A liver cirrhosis and portal hypertension (n = 12), and in healthy controls (n = 10). Baseline filtration rate (GFR) and effective renal plasma flow (ERPF) were significantly lower in patients with cirrhosis than in controls (GFR: mean 88 +/- SD 16 mL/min vs. 106 +/- 15 mL/min, P = .01, ERPF: 477 +/- 93 vs. 561 +/- 72 mL/min, P = .002). In both groups amino acid (aa) infusion increased GFR, ERPF, as well as cGMP and urinary NOx. Changes in GFR were similar in cirrhotic patients and controls (28.3% +/- 14% in cirrhotics and 26% +/- 11% in controls), but the degree of aa-induced changes in ERPF was more marked in patients with liver cirrhosis (31.8% +/- 17% vs. 18.6% +/- 12%, P = .02). Plasma levels of NOx and cGMP were similar in either group at baseline and during aa infusion, whereas NOx and cGMP excretion in cirrhotics was constantly 14% to 24% lower than in the control group. We conclude that patients with compensated liver cirrhosis and portal hypertension already have an impaired kidney function. In addition our data suggest a cirrhosis-related dissociation between ERPF and GFR during aa stimulation. Further studies are warranted to find out whether a local imbalance between vasoconstrictors and vasodilators, e.g., decreased local NO formation, plays a key role for this phenomenon.
...
PMID:Renal functional reserve and nitric oxide in patients with compensated liver cirrhosis. 932 5

Atrial natriuretic peptide is one of a family of natriuretic peptides thought to play a role in the altered sodium balance of advanced liver disease and ascites. Its level is usually increased in the plasma of cirrhotic patients, probably due to relative plasma volume expansion. When exogenous ANP is administered intravenously to dogs or rats with experimental liver cirrhosis and ascites, an heterogeneous natriuretic response is obtained with about half of the population not responding. Similar observations are recorded for patients with clinical cirrhosis. In dogs, attenuation of the ANP-induced natriuresis may depend on a reduction in renal cortical bradykinin activity. In patients with cirrhosis, the ability to release ANP in response to central volume expansion is dissociated from the accompanying natriuresis. Attenuation of the renal tubular response to ANP in this setting may be correlated to the degree of intrahepatic sinusoidal hypertension and associated augmented reflex sympathetic nervous activity to the kidneys. Actual tubular resistance to ANP may be due to reduced Na+ delivery to the inner medullary collecting duct and/or increased degradation of cyclic guanosine monophosphate.
...
PMID:Atrial natriuretic peptide: renal effects in cirrhosis of the liver. 935 63

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.
...
PMID:Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites. 942 86

The aim of this study is to ascertain whether the formation of nitric oxide is argumented in patients with liver cirrhosis and its mechanism. 38 cirrhotic patients and 15 normal controls were studied. Higher plasma levels of NO2-/NO3- (stable end products of nitric oxide), endotoxin, tumor necrosis factor alpha (TNF alpha) and cyclic guanosine monophosphate (cGMP) were observed in patients with cirrhosis than in normal controls (P < 0.01, 0.01, 0.01, 0.05). The higher Child-Pugh, the higher plasma NO2-/NO3- level. The concentration of NO2-/NO3- had a positive correlation with that of endotoxin and TNF alpha (r = 0.481, P < 0.01; r = 0.351, P < 0.05). It is suggested that the production of nitric oxide is augmented and could be induced by endotoxin and TNF alpha. Execessive formation of nitric oxide may be related to hyperdynamic circulation in cirrhosis.
...
PMID:[Nitric oxide levels in cirrhotic patients]. 981 57

Hepatic stellate cells (HSCs) participate in the regulation of hepatic microcirculation and have receptors for many vasoconstrictor factors. It is unknown whether HSCs have receptors for circulating vasodilators such as atrial natriuretic peptide (ANP). This study investigated the presence of ANP receptors in human HSCs and whether ANP antagonizes the effects of endothelin-1 in these cells. ANP receptors were assessed by binding and cross-linking studies, reverse-transcriptase polymerase chain reaction (PCR), and measuring intracellular cyclic guanosine monophosphate concentration. Intracellular calcium concentration ([Ca(2+)](i)) and cell contraction were measured in individual cells loaded with fura-2 using a morphometric method. Binding and cross-linking affinity experiments showed the existence of ANP receptors in human HSCs. PCR products with the expected length were obtained for guanylate cyclase A receptor, the physiological receptor of ANP, both in quiescent and activated human cells. ANP induced a dose-dependent increase in intracellular cyclic guanosine monophosphate concentration and blunted the increase in [Ca(2+)](i) elicited by endothelin-1. Most importantly, ANP markedly reduced cell contraction induced by endothelin-1. HSCs isolated from rats with carbon tetrachloride-induced cirrhosis showed a higher number of ANP receptors compared with HSCs isolated from normal rats, indicating that in vivo activation of HSCs is associated with an up-regulation of ANP receptors. These results indicate that human HSCs have receptors for ANP, the activation of which reduces the effects of endothelin-1 on [Ca(2+)](i) and cell contraction. ANP could participate in regulating the contractility of HSCs by antagonizing the effect of vasoconstrictors.
...
PMID:Atrial natriuretic peptide antagonizes endothelin-induced calcium increase and cell contraction in cultured human hepatic stellate cells. 1042 60

To assess whether an increased production of nitric oxide is involved in the circulatory and renal alterations of cirrhosis, we evaluated systemic hemodynamics (echocardiography), renal hemodynamics, and sodium handling (lithium clearance method), plasma renin activity (PRA), aldosterone (PAC), and norepinephrine in 7 patients (3 men, mean age 65 +/- 2 years) with compensated cirrhosis, portal hypertension, and hyperdynamic circulation during intravenous N(G)-monomethyl-L-arginine (L-NMMA) (3 mg/kg bolus plus 0.05 mg/kg. min for 120 minutes) or placebo (the vehicle) in a randomized, placebo-controlled, crossover study. Administration of L-NMMA resulted in significant reductions in plasma and urinary nitrite levels and plasma cyclic guanosine monophosphate (cGMP), indicating effective inhibition of nitric oxide synthase. L-NMMA also significantly reduced cardiac index (-13%) and increased systemic vascular resistance (+26%), arterial pressure (+9%), renal blood flow (+12%), glomerular filtration rate (+12%), and sodium excretion (+25%). Changes in sodium excretion were caused by both enhanced filtered sodium load and reduced sodium reabsorption in the proximal tubule. Plasma norepinephrine significantly decreased in response to L-NMMA, and there was a trend for reductions in PRA and PAC. Placebo had no appreciable effect on any of the measured parameters. These results indicate that in patients with compensated cirrhosis, portal hypertension and hyperdynamic circulation inhibition of nitric oxide synthase corrects the altered systemic hemodynamics and improves renal function and sodium excretion.
...
PMID:Hemodynamic, renal, and endocrine effects of acute inhibition of nitric oxide synthase in compensated cirrhosis. 1143 29

This study examines the expression and cellular distribution pattern of nitric oxide synthase (NOS) isoforms, nitrotyrosine-derived complexes, and the nitric oxide (NO) production in the cerebellum of rats with cirrhosis induced by thioacetamide (TAA). The results showed local changes in the tissue distribution pattern of the NOS isoforms and nitrated proteins in the cerebellum of these animals. Particularly, eNOS immunoreactivity in perivascular glial cells of the white matter was detected only in TAA-treated animals. In addition, although neither neuronal NOS (nNOS) nor inducible NOS (iNOS) cerebellar protein levels appeared to be affected, the endothelial NOS (eNOS) isoform significantly increased its expression, and NO production slightly augmented in TAA-treated rats. These NOS/NO changes may contribute differently to the evolution of the hepatic disease either by maintaining the guanosine monophosphate-NO signal transduction pathways and the physiological cerebellar functions or by inducing oxidative stress and cell damage. This model gives rise to the hypothesis that the upregulation of the eNOS maintains the physiological production of NO, while the iNOS is silenced and the nNOS remains unchanged. The differential NOS-distribution and expression pattern may be one of the mechanisms involved to balance cerebellar NO production in order to minimize TAA toxic injury. These data help elucidate the role of the NOS/NO system in the development and progress of hepatic encephalopathy associated with TAA cirrhosis.
...
PMID:Upregulation of endothelial nitric oxide synthase maintains nitric oxide production in the cerebellum of thioacetamide cirrhotic rats. 1520 23

Cirrhosis is characterized by altered lipid and protein metabolism and an excessive accumulation of extracellular matrix components. The aim of this work was to determine the effect of dietary nucleotide intake on the intracellular pools of nucleic acids and nucleotides, hepatic redox state, and protein synthesis during cirrhosis. Rats were given 300 mg/L thioacetamide (TAA) in drinking water and were fed diets without (TAA-Nt) or with nucleotides (Nt) (TAA+Nt, 3 g each of AMP, inosine 5'-monophosphate, CMP, GMP, and UMP per kg diet) for 4 mo. The degree of liver histological injury was less in group TAA+Nt than in TAA-Nt. The intake of nucleotides significantly increased the hepatic concentration of total nucleotides, adenine nucleotides, and ATP+ADP+AMP. Interestingly, the concentration of CDP-choline, a nucleotide necessary for phospholipid synthesis, was significantly higher in TAA+Nt than in TAA-Nt. The hepatic pyruvate:lactate (P = 0.075) and acetoacetate:beta-hydrodybutyrate (P < 0.05) ratios, indicators of cytosolic and mitochondrial redox states, were lower in TAA-Nt than in TAA+Nt. The total protein concentration was higher in the livers of TAA+Nt than in TAA-Nt. Although there were no differences in the expression of the albumin gene, the hepatic albumin concentration was significantly higher in TAA+Nt than in TAA-Nt. These data indicate that the reduction of liver injury in nucleotide-supplemented rats may be due to the increased intracellular availability of key metabolic nucleotides, the restoration of mitochondrial function, and the augmentation of protein synthesis.
...
PMID:Dietary nucleotides enhance the liver redox state and protein synthesis in cirrhotic rats. 1546 38


<< Previous 1 2 3 Next >>

---