Acute effects of moderate dehydration on the hepatic conversion of amino nitrogen into urea nitrogen in healthy men.
Intracellular hydration may play a role in the regulation of protein and nitrogen metabolism. The hepatic removal of nitrogen by urea synthesis has a key regulatory role in nitrogen balance. The purpose of the present study was to establish the acute effects of dehydration on the hepatic kinetics of urea synthesis, quantified by functional hepatic nitrogen clearance (FHNC), in healthy volunteers. Seven healthy men were studied twice in random order. On both study days, a primed continuous infusion of alanine was given. On the day of dehydration an intravenous bolus injection of a loop diuretic (furosemide, 1 mg/kg) was superimposed. FHNC was calculated as the ratio between measured synthesis rates of urea nitrogen and blood alanine concentrations. Furosemide induced a weight loss of 1 kg. During dehydration, FHNC decreased by approx. 25% (41+/-11 to 54+/-10 litres/h; P<0.02). On both occasions individual FHNC and glucagon values were positively correlated (r(2)>0.6). In addition, dehydration more than halved the linear slope of the relationship (P<0.05). The FHNC values were correlated with the urinary excretion of both potassium and sodium (r(2)=0.68, P<0.01 and r(2)=0.62, P<0.02 respectively). Changes in the reactivity of urea synthesis to glucagon (i.e. the ratio between FHNC and glucagon concentration) was negatively correlated with an indirectly estimated change in intracellular water (r(2)=0.79, P<0.05). We conclude that acute moderate dehydration down-regulates both total urea synthesis and its sensitivity to glucagon. The latter was related to estimated intracellular water loss. Dehydration may thus have nitrogen-saving consequences with regard to the hepatic contribution to whole-body nitrogen homoeostasis. The mechanism of this effect and the relationship with sodium and potassium fluxes is not known.
Ivarsen
P
P
Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark. pi@dadlnet.dk
Greisen
J
J
Vilstrup
H
H
D000208:Acute Disease; D000328:Adult; D000409:Alanine / Q000494:pharmacology; D018592:Cross-Over Studies; D003681:Dehydration / Q000139:chemically induced / Q000378:metabolism*; D004232:Diuretics; D005665:Furosemide; D005934:Glucagon / Q000097:blood; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D009584:Nitrogen / Q000378:metabolism*; D011188:Potassium / Q000652:urine; D012964:Sodium / Q000652:urine; D014508:Urea / Q000378:metabolism*; D014882:Water-Electrolyte Balance
D004232:Diuretics; D005665:Furosemide; D014508:Urea; D005934:Glucagon; D012964:Sodium; D009584:Nitrogen; D000409:Alanine; D011188:Potassium