Opioid receptor blockade improves mesenteric responsiveness in biliary cirrhosis

Mohammad Ebrahimkhani, Leila Moezi, Samira Kiani, Shahin Merat, Ahmad R. Dehpour

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Arterial vasodilation with concomitant hyperdynamic circulation is a common finding in cirrhotic subjects. Elevated levels of plasma endogenous opioid peptides have been reported in cholestasis and cirrhosis. Increased opioid peptides contribute to different manifestations of chronic liver disease such as pruritis, ascitis, and hepatic encephalopathy. In this study the potential role of opioid system in cirrhosis-induced vascular hyporesponsiveness was investigated. Bile duct ligated and sham operated animals received daily subcutaneous administration of naltrexone, an opioid receptor antagonist (20 mg/kg/day), or saline for 28 days. After 4 weeks the superior mesenteric artery was cannulated and was perfused according to McGregor method and then phenylephrine vasoconstrictor response of mesenteric vessels (10-10 to 10-6 mol) was examined. In order to evaluate the effects of acute opioid receptor blockade, additional groups of animals were treated by acute single intraperitoneal naltrexone injection (20 mg/kg). Plasma level of nitrite/nitrate as an indicator for nitric oxide production was measured. Biliary cirrhosis was accompanied with a decrease in baseline perfusion pressure in mesenteric vascular bed (P < 0.01). Chronic opioid receptor blockade significantly increased this parameter (P < 0.01). The maximum pressure response to phenylephrine was decreased significantly in cirrhosis while chronic naltrexone treatment completely improved it (P < 0.01). Acute single injection of naltrexone could not influence the understudied homodynamic parameters. Chronic opioid receptor blockade did not modulate the increased nitrite/nitrate levels following cholestasis. This study provided evidence on the contribution of endogenous opioid system to vascular hyporesponsiveness in cirrhosis which is not directly correlated to high plasma NO levels.

Original languageEnglish (US)
Pages (from-to)3007-3011
Number of pages5
JournalDigestive Diseases and Sciences
Volume53
Issue number11
DOIs
StatePublished - Nov 2008
Externally publishedYes

Fingerprint

Naltrexone
Biliary Liver Cirrhosis
Opioid Receptors
Fibrosis
Blood Vessels
Opioid Peptides
Cholestasis
Phenylephrine
Nitrites
Nitrates
Opioid Analgesics
Pressure
Superior Mesenteric Artery
Narcotic Antagonists
Hepatic Encephalopathy
Vasoconstrictor Agents
Pruritus
Bile Ducts
Intraperitoneal Injections
Vasodilation

Keywords

  • Bile duct ligated
  • Biliary cirrhosis
  • Endogenous opioids
  • Mesenteric vascular bed
  • Naltrexone
  • Nitric oxide

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Opioid receptor blockade improves mesenteric responsiveness in biliary cirrhosis. / Ebrahimkhani, Mohammad; Moezi, Leila; Kiani, Samira; Merat, Shahin; Dehpour, Ahmad R.

In: Digestive Diseases and Sciences, Vol. 53, No. 11, 11.2008, p. 3007-3011.

Research output: Contribution to journalArticle

Ebrahimkhani, M, Moezi, L, Kiani, S, Merat, S & Dehpour, AR 2008, 'Opioid receptor blockade improves mesenteric responsiveness in biliary cirrhosis', Digestive Diseases and Sciences, vol. 53, no. 11, pp. 3007-3011. https://doi.org/10.1007/s10620-008-0261-7
Ebrahimkhani, Mohammad ; Moezi, Leila ; Kiani, Samira ; Merat, Shahin ; Dehpour, Ahmad R. / Opioid receptor blockade improves mesenteric responsiveness in biliary cirrhosis. In: Digestive Diseases and Sciences. 2008 ; Vol. 53, No. 11. pp. 3007-3011.
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