Gastroenterology

Gastroenterology

Volume 116, Issue 2, February 1999, Pages 387-393
Gastroenterology

Liver, Pancreas, and Biliary Tract
Altered adrenergic responsiveness of endothelium-denuded hepatic arteries and portal veins in patients with cirrhosis☆

Dedicated to Professor Dr. G. Strohmeyer on the occasion of his 70th birthday.
https://doi.org/10.1016/S0016-5085(99)70136-8Get rights and content

Abstract

Background & Aims: Patients with cirrhosis are characterized by a reduced splanchnic vascular resistance and a hyporeactivity to adrenergic vasoconstrictors. So far, their adrenergic splanchnic vascular responsiveness has not been evaluated in vitro. We compared responses to α1- and β2-adrenoceptor stimulation of hepatic arteries and portal veins of patients with cirrhosis undergoing transplantation with those of organ donors. Methods: Isometric contractions of endothelium-denuded vessel rings were induced cumulatively by methoxamine and relaxations by isoproterenol. Results are expressed as percentage of the contraction obtained by 85 mmol/L KCl or of the relaxation obtained by 100 μmol/L papaverine, respectively. Results: Maximal methoxamine-induced contractions were reduced in cirrhotic hepatic arteries (cirrhosis, 51.8% ± 6.8%; donor, 89.9% ± 6.6%; P < 0.01) and portal veins (cirrhosis, 49.2% ± 6.4%; donor, 94.0% ± 5.3%; P < 0.01). In cirrhosis, isoproterenol induced a less marked relaxation of hepatic arteries (cirrhosis, 46.6% ± 3.2%; donor, 100.3% ± 4.4%; P < 0.01) but an increased relaxation of portal veins (cirrhosis, 41.9% ± 6.2%; donor, 26.2% ± 2.8%; P < 0.01). Conclusions: In cirrhosis, endothelium-free hepatic arteries are hyporeactive to α1- and β2-adrenoceptor agonists, and portal veins are hyporeactive to α1- but hyperreactive to β2-adrenoceptor agonists. These findings support the in vivo findings of a hyporesponsiveness to adrenergic vasoconstrictors in patients with cirrhosis.

GASTROENTEROLOGY 1999;116:387-393

Section snippets

Patients and methods

From 33 cirrhotic patients undergoing liver transplantation (15 women, 18 men; 45.1 ± 2.5 years; 9 Child–Pugh A, 12 Child–Pugh B, 12 Child–Pugh C), 28 segments of the hepatic arteries and 17 segments of the portal veins were obtained. Twenty corresponding specimens of the hepatic arteries and 19 of the portal veins from 30 organ donors (10 women, 20 men; 40.3 ± 3.0 years) served as controls. The cause of cirrhosis was hepatitis B in 13 patients, alcohol in 7, hepatitis C in 4, autoimmune

Results

UW solution did not affect the maximum contraction of pig mesenteric arteries by 85 mmol/L KCl (without UW solution, 3.7 ± 0.48 g; after 5-hour incubation in UW solution, 3.78 ± 0.09 g; n = 4), or by 10−3 mol/L methoxamine (without UW solution, 43.8% ± 7.2%; after 5-hour incubation in UW solution, 44.6% ± 6.2%; n = 4).

The KCl-induced maximum contraction of portal veins and hepatic arteries was not different in organ donors and transplant recipients (Table 1). The methoxamine-induced

Discussion

In the present study, we found that endothelium-denuded splanchnic vessels from patients with cirrhosis show an impaired contraction to α1-adrenoceptor stimulation compared with vessels from noncirrhotic organ donors. Such an altered response was also observed for relaxation experiments with cirrhotic hepatic arteries, whereas portal veins showed an enhanced relaxation on β2-adrenoceptor stimulation in comparison to the donors. Several investigators have suggested that a hyporesponsiveness of

Acknowledgements

The authors thank Dr. H. Berthold, Dr. M. Flesch, and Prof. Dr. Böhm for excellent advice.

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    Address requests for reprints to: Jörg Heller, M.D., c/o Prof. Dr. Tilman Sauerbruch, Department of General Internal Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. Fax: (49) 228-287-4322.

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    Copyright © 1999 American Gastroenterological Association. Published by Elsevier Inc. All rights reserved.