guanosine-monophosphate and Liver-Cirrhosis

In order to assess the possible participation of nitric oxide (NO) in renal function during compensated hepatic cirrhosis, we studied renal function, the plasma and urinary levels of cGMP and the concentration of nitrates and nitrites, as markers of NO synthesis in blood and urine, in 10 patients with Child A hepatic cirrhosis as compared with 10 control subjects, both under basal conditions and during stimulation (amino acid-induced glomerular hyperfiltration).. To study renal function, the glomerular filtration rate (GFR), effective renal plasma flow (ERPF), renal functional reserve (RFR), renal venous resistance (RVR) and the filtration fraction (FF) were measured. Renin and aldosterone levels were determined to assess the possible involvement of these compounds in the renin-angiotensin-aldosterone axis.. GFR and ERPF were significantly lower in the patients with cirrhosis than in the controls (mean GFR: 82+/-12.3 vs. 105+/-15 ml/min, p = 0. 01; ERPF 452+/-86 vs. 543+/-56 ml/min, p = 0.002). The RFR value was similar in both groups. In the basal situation cGMP levels were higher in plasma and urine in patients with cirrhosis than in the controls (plasma cGMP in cirrhosis 8.4+/-2.4 vs. 4.2+/-3.5 pmol/ml; urine cGMP in cirrhosis 1.2+/-2.1 vs. 0.68+/-0.1 pmol/ml). The NO levels were also higher in plasma and urine in patients with cirrhosis vs. controls (plasma NO in cirrhosis 45.5+/-9.2 vs. 30. 3+/-1.2 micromol/l; urinary NO in cirrhosis 6.2+/-1.3 vs. 3.1+/-2.3 micromol/ml). In both groups the amino acid perfusion increased GFR, ERPF, cGMP and NO levels in plasma and urine. In the patients with cirrhosis the RVR decreased significantly during perfusion and no noteworthy changes in FF were observed. The GFR values observed during amino acid perfusion were similar in patients with cirrhosis and portal hypertension to those observed in the controls (27.2+/-12 vs. 25.3+/-16%). However, the changes induced the ERPF were more marked in patients with cirrhosis (cirrhosis 35.3+/-15 vs. 22. 2+/-13%, p = 0.02).. The present findings point to certain alterations in renal function in patients with hepatic cirrhosis and portal hypertension without ascitis, a clear difference being visible between the ERPF and GFR following amino acid-induced stimulation. The significant elevation in cGMP and NO levels in plasma and urine implies a maintained vasodilatory action that may at least partly compensate the vasoconstrictor effects of angiotensin II.

Topics: Adult; Aged; Amino Acids; Female; Glomerular Filtration Rate; Guanosine Monophosphate; Humans; Infusions, Intravenous; Liver Cirrhosis; Male; Middle Aged; Nitric Oxide; Probability; Reference Values; Renal Plasma Flow, Effective; Severity of Illness Index

Transjugular intrahepatic portosystemic stent-shunt (TIPSS) reduces the portal pressure gradient and leads to better control of ascites. The aim of this study was to evaluate (1) changes in renal handling of sodium following TIPSS and (2) the mechanism of these changes.. Prospective study.. Tertiary referral centre for liver diseases.. Eighteen patients with ascites undergoing TIPSS for recurrent variceal haemorrhage (16) (3 or more hospital admissions because of variceal haemorrhage whilst being treated endoscopically) or refractory ascites (2) were studied. Urinary sodium (UNa), creatinine clearance (CrCl), plasma renin activity (PRA), atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), Angiotensin II (AII) and lithium clearance (LiCl) were measured before and 3 months after TIPSS when portography was performed and the portal pressure gradient (PPG) also measured. All patients were haemodynamically stable and had received no diuretics for at least 1 week before blood sampling.. Improvement in ascites was achieved in all patients in whom TIPSS was inserted successfully (reduction in PPG to < 12 mmHg). PPG was reduced from a mean of 19 (+/-6) to 8.8 (+/-3.4) mmHg (P < 0.001). Urinary sodium and creatinine clearance improved significantly following TIPSS (P < 0.001, P < 0.001, respectively). PRA, All, cGMP and LiCl were abnormal before TIPSS and improved significantly following TIPSS (P < 0.007, P < 0.001, P < 0.001 and P < 0.01, respectively). ANP was not significantly different from normal controls and did not change significantly following TIPSS. Changes in UNa did not correlate with the Pugh score or the change in PPG.. The results of this study show that TIPSS is associated with significant improvement in UNa, CrCl, PRA, AII, cGMP and LiCl. The change in UNa following TIPSS was independent of the severity of underlying liver disease or the change in PPG.

Topics: Adult; Angiotensin II; Ascites; Female; Guanosine Monophosphate; Humans; Kidney Function Tests; Lithium; Liver Cirrhosis; Male; Middle Aged; Portasystemic Shunt, Transjugular Intrahepatic; Prognosis; Prospective Studies; Radioimmunoassay; Reference Values; Renin; Severity of Illness Index; Sodium

An increased release of nitric oxide (NO), a powerful vasodilating agent, has been proposed to play a role in the pathogenesis of vasodilation and hyperdynamic circulation associated with advanced cirrhosis. We evaluated NO synthase (NOS) activity in peripheral leukocytes of 12 cirrhotic patients and 9 healthy subjects together with plasma endotoxin levels and systemic hemodynamic (by a noninvasive echocardiographic method). NOS activity was evaluated by (1) measuring the capacity of isolated polymorphonuclear cells (PMNs) and monocytes to convert [3H]arginine to [3H]citrulline; (2) measuring the ability of neutrophils and monocytes to inhibit thrombin-induced platelet aggregation and to increase guanosine 3'-5'-cyclic monophosphate content in coincubated platelets, an expression of NO release from these cells. Both neutrophils and monocytes from cirrhotic patients produced significantly higher amounts of [3H]citrulline than cells obtained from healthy subjects (P < .001 and P < .02 for neutrophils and monocytes, respectively) and were more effective than control cells in inhibiting platelet aggregation (P < .05 and P < .001, respectively for 2 x 10(6) cells) and in increasing guanosine 3'-5'-cyclic monophosphate content in coincubated platelets (P < .05 and P < .001, respectively). The anti-aggregating activity expressed by leukocytes has a pharmacological profile similar to that described for NO, because it increased after addition of superoxide dismutase, a superoxide anion scavenger, and markedly decreased after inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine-methyl ester (L-NAME). Cirrhotic patients had significantly higher plasma endotoxin levels (P < .001) and cardiac index (P < .01) when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Arginine; Ascites; Blood Platelets; Citrulline; Enzyme Inhibitors; Female; Guanosine Monophosphate; Heart Rate; Humans; Lipopolysaccharides; Liver Cirrhosis; Male; Middle Aged; Monocytes; Neutrophils; Nitric Oxide; Nitric Oxide Synthase; Platelet Aggregation; Platelet Aggregation Inhibitors; Stroke Volume; Tritium