Contractile response of isolated human hepatic arteries to α-adrenoceptor agonists is not impaired in patients with cirrhosis

Abstract

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 alpha-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. alpha-Adrenoceptor-mediated contraction was assessed by constructing cumulative concentration-response curves to the alpha1-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.

Cyclooxygenase-2 and inducible nitric oxide synthase in omental arteries harvested from patients with severe liver diseases: immuno-localization and influence on vascular tone

“…The mechanisms of this hyper-reactivity are unknown but a similar observation has been reported in human hepatic conduit arteries [23] and in omental arteries from septic shock patients [12]: it may correspond to an adaptive mechanism to inflammatory injuries in order to counterbalance an increased production or the action of endothelins [24,25]. Another explanation could be a shift of the arachidonic acid metabolism toward the leukotriene pathway because COXs are inhibited [26].…”

Norepinephrine in Small-For-Size Liver Grafts: An Experimental Study in Pigs

“…Norepinephrine could be one of them. It is known that it produces contraction to hepatic artery, which is unaffected by cirrhosis or by preservation with the University of Wisconsin's solution, which is used for liver transplantation [6,7]. Hickman et al have also outlined that persistent elevation of plasma norepinephrine after reduced liver grafting might have contributed to the diminished hepatic arterial flow [4].…”

“…It is known that it produces ␣-adrenoceptor-mediated contraction to hepatic vessels [6,7]. Liver resection and liver transplantation have been found to increase plasma norepinephrine levels [8,9].…”

Adrenergic Response of Splanchnic Arteries from Cirrhotic Patients: Role of Nitric Oxide, Prostanoids, and Reactive Oxygen Species

“…With regard to the response of human blood vessels to adrenergic stimulation, the data reported are contradictory because this response can be decreased (3, 4) or unaltered (5,6). Human hepatic artery has been used to examine the responsiveness of blood vessels from cirrhotic patients, and this artery is considered to be suitable because it is from a vascular territory (splanchnic), which is known to be dilated in cirrhosis (16).…”

“…With regard to adrenergic reactivity, there are data showing that the response of hepatic arteries from cirrhotic patients to a1-adrenoceptor stimulation is decreased (3,4). Other studies, however, report that hepatic arteries (5) or mesenteric arteries (6) from cirrhotic patients exhibit unaltered response to a-adrenoceptor and to a1-adrenoceptor stimulation. As far as we know, only one study has been made to examine the response to both selective a1 and a2 adrenergic stimulation, and that study was performed in vivo, evaluating blood pressor response (7).…”