1.Impaired vasoconstriction in animals with cirrhosis is maintained in isolated vessels in vitro, indicating an intrinsic alteration in function or structure of the cells in the vascular wall. This may be due to receptor down-regulation, a defect in post-receptor signal transduction or overproduction of vasodilator compounds. This investigation examined the role of these mechanisms in modulating α-adrenoceptor-mediated contraction in hepatic arteries from patients with advanced cirrhosis.
2.Hepatic arteries were obtained from subjects with and without cirrhosis for functional investigation in vitro. Endothelial cell function was assessed using endothelium-dependent (acetylcholine) and independent (3′-morpholinosydnonimine) vasodilators. α-Adrenoceptor-mediated contraction was assessed by constructing cumulative concentration–response curves to the α1-selective agonist phenylephrine, the non-selective adrenoceptor agonist noradrenaline and the receptor-independent vasoconstrictor potassium chloride.
3.None of the vessels used in this study had an intact endothelium but endothelium-independent relaxation was not different in arteries from subject with (79.5±10.16%; n = 23) and without (84.45±18%; n = 20) cirrhosis. Phenylephrine, noradrenaline and potassium chloride produced contractions that were of similar size (P> 0.05) in arteries from subjects with (10.10±0.97 ;g, 8.85±1.03 ;g and 8.56±0.65 ;g respectively) and without (10.42±1.23 ;g, 9.58±1.39 ;g and 8.62±0.98 ;g respectively) cirrhosis. The sensitivities (pD2) of the responses to these agonists were also similar (P< 0.05) in arteries from patients with cirrhosis (5.45±0.10, 5.60±0.12 and 1.57±0.03 respectively) and those from non-cirrhotic donors (5.58±0.11, 5.67±0.11 and 1.54±0.05 respectively).
4.Contraction of the denuded hepatic artery was unaffected by cirrhosis indicating that vascular abnormalities in this condition in man are not due to an intrinsic alteration of smooth muscle cell function in hepatic conduit arteries.
Present address: Dr J. F. Dillon, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K.