EFFECT OF ORAL PROPRANOLOL ADMINISTRATION ON AZYGOS, RENAL AND HEPATIC-UPTAKE AND OUTPUT OF CATECHOLAMINES IN CIRRHOSIS

Circulating catecholamines are increased in cirrhosis with portal hypertension, and increase further after propranolol. In 23 cirrhotic patients, plasma norepinephrine and epinephrine were determined in an artery, the azygos vein, the right renal vein and a hepatic vein before and after an oral 80-mg dose of propranolol. Baseline azygos and renal venous norepinehrine levels were significantly higher than arterial norepinephrine levels (+20%, p < 0.005; and +28%, p < 0.001, respectively). Hepatic venous norepinephrine and all venous epinephrine values were below the arterial values (all p < 0.05). After propranolol intake, arterial norepinephrine and epinephrine increased (+16%, p < 0.01; and +93%, p < 0.001, respectively). Significant increases in norepinephrine and epinephrine were found in azygos and renal veins (all p < 0.01), whereas hepatic venous norepinephrine and epinephrine remained unchanged. Azygos and hepatic blood flow decreased after propranolol intake (-27%, p < 0.05; and -16%, p < 0.01, respectively). Azygos spillover of norepinephrine (an estimate of locally released norepinephrine delivered to the circulation) and clearance of epinephrine remained unaltered. Hepatointestinal clearance showed no significant change for norepinephrine, but showed a borderline-significant decrease for epinephrine (-23%, p = 0.08). Our results show a net production of norepinephrine in the prehepatic splanchnic area drained through superior portalsystemic collaterals and in the kidneys. The increase in circulating catecholamines after propranolol intake is probably due to a combination of further enhancement of sympathetic activity and a decrease in catecholamine degradation.