Effects of beta-blockade on hepatic conversion of amino acid nitrogen and on urea synthesis in cirrhosis.
beta-Blockers are widely used to prevent gastrointestinal hemorrhage in cirrhosis. The metabolic effects of treatment are scarcely studied: hepatic function reportedly does not change significantly, but beta-adrenoceptors have been reported to regulate protein and amino acid metabolism. We studied hepatic nitrogen metabolism in response to constant alanine infusion in seven patients with cirrhosis before and 7 to 10 days after treatment with oral propranolol (60 to 100 mg/d). Beta-blockade was effective: it decreased heart rate by 25%, abolished orthostatic tachycardia, and reduced portal blood flow by 20%. Alanine-stimulated urea nitrogen synthesis rate (UNSR) was higher in patients with propranolol treatment, without any difference in aminonitrogen concentration. The kinetics of hepatic conversion of amino acid nitrogen into urea--ie, functional hepatic nitrogen clearance (FHNC)--increased by 30%, from (mean +/- SD) 17.0 +/- 4.1 to 22.0 +/- 6.6 L/h (P < .01). Increased urea production during alanine infusion resulted in negative nitrogen exchange even at the peak of alpha-aminonitrogen concentration. Basal insulin level was only slightly reduced during propranolol treatment, whereas the insulin response to alanine was significantly blunted. No differences in glucagon and cortisol were demonstrated. Epinephrine and norepinephrine levels were high-normal and did not vary after treatment. Increased urea production and stimulation of hepatic nitrogen clearance during beta-blockade may be mediated by relative hypoinsulinemia or by direct involvement of beta-adrenoceptors in the control of nitrogen metabolism, possibly by regulation of amino acid uptake and release in peripheral tissues.
Fabbri
A
A
Istituto di Clinica Medica Generale e Terapia Medica, Università di Bologna, Italy.
Bianchi
G P
GP
Brizi
M
M
Bugianesi
E
E
Grossi
G
G
Flamia
R
R
Zoli
M
M
Marchesini
G
G
D000368:Aged; D000409:Alanine / Q000008:administration & dosage; D000596:Amino Acids / Q000097:blood / Q000378:metabolism*; D001794:Blood Pressure; D002395:Catecholamines / Q000097:blood; D005260:Female; D006339:Heart Rate; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000627:therapeutic use*; D014508:Urea / Q000378:metabolism*
D000596:Amino Acids; D002395:Catecholamines; D014508:Urea; D011433:Propranolol; D000409:Alanine