Rapid Communication
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 7, 2006; 12(13): 2095-2102
Published online Apr 7, 2006. doi: 10.3748/wjg.v12.i13.2095
Local regulator adrenomedullin contributes to the circulatory disturbance in cirrhotic rats
Shinya Sakurai, Hideyuki Kojima, Masahito Uemura, Hiroyasu Satoh, Hiroshi Fukui
Shinya Sakurai, Hideyuki Kojima, Masahito Uemura, Hiroshi Fukui, Third Department of Internal Medicine, Nara Medical University, 840 Shijo-cho Kashihara-shi, Nara 634-8522, Japan
Hiroyasu Satoh, Department of Pharmacology, Nara Medical University, 840 Shijo-cho Kashihara-shi, Nara 634-8522, Japan
Author contributions: All authors contributed equally to the work.
Supported by Grant-in-Aid for Scientific Research, No. 17590669
Correspondence to: Hideyuki Kojima, Third Department of Internal Medicine, Nara Medical University, 840 Shijo-cho Kashihara-shi, Nara 634-8522, Japan. kojima@nmu-gw.naramed-u.ac.jp
Telephone: +81-744-223051
Received: October 31, 2005
Revised: November 11, 2005
Accepted: November 15, 2005
Published online: April 7, 2006
Abstract

AIM: To investigate whether adrenomedullin, a potent vasodilator peptide, plays a role in the circulatory disturbance in cirrhosis.

METHODS: Cirrhosis was induced in rats by weekly gavage of carbon tetrachloride. Hemodynamic studies were performed in vivo using radioactive microspheres and in vitro using isolated aortic rings. The adrenomedullin concentrations were measured by radioimmunoassay.

RESULTS: Acute administration of adrenomedullin to the control rats reduced the systemic arterial pressure along with an increase of serum levels of the stable metabolite of nitric oxide (NOx), in a dose-dependent manner. Chronic infusion of adrenomedullin reduced the vascular resistance and increased the blood flow in the systemic and splanchnic circulation. Intravenous administration of anti-adrenomedullin antibody did not affect any hemodynamic parameters in the cirrhotic rats, whereas this antibody ameliorated the blunted contractile response to phenylephrine, α-adrenergic receptor agonist, in the aortic rings of the cirrhotic rats. The adrenomedullin concentrations in the aorta were higher in the cirrhotic rats than in the controls, and correlated with the mean arterial pressure in the cirrhotic rats. Moreover, adrenomedullin blunted the contractile response to phenylephrine in both of the control aorta and cirrhotic aorta, but not in the presence of NG-nitro-L-arginine methyl ester, an NO synthase inhibitor.

CONCLUSION: Adrenomedullin overproduced in the vascular wall may contribute to the circulatory disturbance in cirrhosis as a local regulator of the vascular tonus rather than a circulating hormone.

Keywords: Adrenomedullin; Liver cirrhosis; Vasodilation; Circulatory disturbance; Vascular tonus; Circulating hormone