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


METHODS
The effects of N(G)-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 microg/kg/min, and five patients (High) received 25, 50, and 100 microg/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 (99m)Tc-diethylenetriamine-pentaacetate and (131)I-Hippuran.


RESULTS
L-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).


CONCLUSIONS
Despite 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.
Thiesson
Helle C
HC
Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark.
Skøtt
Ole
O
Jespersen
Bente
B
Schaffalitzky de Muckadell
Ove B
OB
D000804:Angiotensin II / Q000502:physiology; D001201:Ascites / Q000188:drug therapy* / Q000209:etiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000502:physiology; D012083:Renin / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D014867:Water / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D014867:Water; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D012964:Sodium; D019001:Nitric Oxide Synthase; D012083:Renin; D009638:Norepinephrine