Nitric oxide synthase inhibition does not improve renal function in cirrhotic patients with ascites

Thiesson, Helle C.; Skøtt, Ole; Jespersen, Bente; Schaffalitzky de Muckadell, Ove B.
January 2003
American Journal of Gastroenterology;Jan2003, Vol. 98 Issue 1, p180
Academic Journal
: ObjectivesBased mainly on animal experiments, nitric oxide (NO) has been proposed to account for the peripheral arterial vasodilation and hyperdynamic circulation in liver cirrhosis. The aim of this study was to clarify whether a reduction of NO synthesis would ameliorate the circulatory and renal dysfunction in decompensated cirrhotic patients.: MethodsThe effects of NG-monomethyl-L-arginine-acetate (L-NMMA), an NO synthesis inhibitor, were studied. After a 60-min basal period, a total of 10 patients received increasing doses of L-NMMA, five patients (Low) received 12.5, 25, and 50 μg/kg/min, and five patients (High) received 25, 50, and 100 μg/kg/min as a constant infusion during 3 h, followed by a postinfusion period. Five patients (Placebo) received saline infusions only. Glomerular filtration rate and renal plasma flow were measured by clearance techniques with 99mTc-diethylenetriamine-pentaacetate and 131I-Hippuran.: ResultsL-NMMA infusion resulted in an increased blood pressure, decreased heart rate, and dose-dependent suppression of renin of up to 42.1 ± 7.1% (p < 0.01) and angiotensin II of up to 39.9 ± 9.6%, (p < 0.01) levels. Sodium and water excretion were not improved, most likely because of a reduction in renal blood flow of up to 29.1 ± 8.1% (p < 0.01).: ConclusionDespite a partial correction of the hyperdynamic circulation, inhibition of NO synthesis does not improve sodium and water excretion in decompensated cirrhosis, probably because of an accompanying decrease in renal plasma flow. Intrarenal NO synthesis may be important for maintaining intrarenal hemodynamics in decompensated cirrhotic patients.


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