Reduced susceptibility to epinephrine-induced arrhythmias in cirrhotic rats: The roles of nitric oxide and endogenous opioid peptides

Sina Tavakoli, Amir R. Hajrasouliha, Pejman Jabehdar-Maralani, Farzad Ebrahimi, Amirreza Solhpour, Hamed Sadeghipour, Mehdi Ghasemi, Ahmad R. Dehpour

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background/Aims: The clinical relevance of QT prolongation, the most widely recognized cardiac electrophysiological abnormality of cirrhosis, is still undefined. The aim of this study is to examine the susceptibility of chronic (4-week) bile duct-ligated rats to epinephrine-induced arrhythmias. The roles of nitric oxide and endogenous opioids were also evaluated. Methods: Sham-operated and cirrhotic rats were treated with daily subcutaneous administrations of normal saline (1 ml/kg/day), l-NAME (a non-selective nitric oxide synthase inhibitor, 3 mg/kg/day), and naltrexone (20 mg/kg/day) during the fourth week after operation. In order to evaluate the effects of acute nitric oxide synthesis inhibition, additional groups of animals were treated by acute intraperitoneal l-NAME injections (3 mg/kg). Arrhythmias were induced by intravenous injections of 10 μg/kg epinephrine. Results: Despite QT prolongation (P < 0.001), epinephrine induced fewer arrhythmias in cirrhotic rats compared to sham-operated animals (P < 0.05). Chronic, but not acute, l-NAME administration corrected the QT prolongation in cirrhotic rats (P < 0.001), and restored the susceptibility of cirrhotic rats to arrhythmias (P < 0.05). Naltrexone injection without a significant effect on epinephrine-induced arrhythmias corrected QT interval in cirrhotic rats (P < 0.001). Conclusions: This study shows that despite QT prolongation, cirrhotic animals are resistant against epinephrine-induced arrhythmias. This resistance is mediated by chronic nitric oxide overproduction.

Original languageEnglish (US)
Pages (from-to)432-439
Number of pages8
JournalJournal of Hepatology
Volume46
Issue number3
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Fingerprint

Opioid Peptides
Epinephrine
Cardiac Arrhythmias
Nitric Oxide
Naltrexone
Injections
Bile Ducts
Nitric Oxide Synthase
Intravenous Injections
Opioid Analgesics
Fibrosis

Keywords

  • Bile duct-ligation
  • Cirrhosis
  • Endogenous opioid peptides
  • Epinephrine-induced arrhythmias
  • Nitric oxide (NO)
  • Premature ventricular contraction (PVC)
  • QT prolongation
  • Ventricular tachycardia (VT)

ASJC Scopus subject areas

  • Hepatology

Cite this

Reduced susceptibility to epinephrine-induced arrhythmias in cirrhotic rats : The roles of nitric oxide and endogenous opioid peptides. / Tavakoli, Sina; Hajrasouliha, Amir R.; Jabehdar-Maralani, Pejman; Ebrahimi, Farzad; Solhpour, Amirreza; Sadeghipour, Hamed; Ghasemi, Mehdi; Dehpour, Ahmad R.

In: Journal of Hepatology, Vol. 46, No. 3, 01.03.2007, p. 432-439.

Research output: Contribution to journalArticle

Tavakoli, S, Hajrasouliha, AR, Jabehdar-Maralani, P, Ebrahimi, F, Solhpour, A, Sadeghipour, H, Ghasemi, M & Dehpour, AR 2007, 'Reduced susceptibility to epinephrine-induced arrhythmias in cirrhotic rats: The roles of nitric oxide and endogenous opioid peptides', Journal of Hepatology, vol. 46, no. 3, pp. 432-439. https://doi.org/10.1016/j.jhep.2006.09.013
Tavakoli, Sina ; Hajrasouliha, Amir R. ; Jabehdar-Maralani, Pejman ; Ebrahimi, Farzad ; Solhpour, Amirreza ; Sadeghipour, Hamed ; Ghasemi, Mehdi ; Dehpour, Ahmad R. / Reduced susceptibility to epinephrine-induced arrhythmias in cirrhotic rats : The roles of nitric oxide and endogenous opioid peptides. In: Journal of Hepatology. 2007 ; Vol. 46, No. 3. pp. 432-439.
@article{35d5ad7a5d614a93a1bba232613955b8,
title = "Reduced susceptibility to epinephrine-induced arrhythmias in cirrhotic rats: The roles of nitric oxide and endogenous opioid peptides",
abstract = "Background/Aims: The clinical relevance of QT prolongation, the most widely recognized cardiac electrophysiological abnormality of cirrhosis, is still undefined. The aim of this study is to examine the susceptibility of chronic (4-week) bile duct-ligated rats to epinephrine-induced arrhythmias. The roles of nitric oxide and endogenous opioids were also evaluated. Methods: Sham-operated and cirrhotic rats were treated with daily subcutaneous administrations of normal saline (1 ml/kg/day), l-NAME (a non-selective nitric oxide synthase inhibitor, 3 mg/kg/day), and naltrexone (20 mg/kg/day) during the fourth week after operation. In order to evaluate the effects of acute nitric oxide synthesis inhibition, additional groups of animals were treated by acute intraperitoneal l-NAME injections (3 mg/kg). Arrhythmias were induced by intravenous injections of 10 μg/kg epinephrine. Results: Despite QT prolongation (P < 0.001), epinephrine induced fewer arrhythmias in cirrhotic rats compared to sham-operated animals (P < 0.05). Chronic, but not acute, l-NAME administration corrected the QT prolongation in cirrhotic rats (P < 0.001), and restored the susceptibility of cirrhotic rats to arrhythmias (P < 0.05). Naltrexone injection without a significant effect on epinephrine-induced arrhythmias corrected QT interval in cirrhotic rats (P < 0.001). Conclusions: This study shows that despite QT prolongation, cirrhotic animals are resistant against epinephrine-induced arrhythmias. This resistance is mediated by chronic nitric oxide overproduction.",
keywords = "Bile duct-ligation, Cirrhosis, Endogenous opioid peptides, Epinephrine-induced arrhythmias, Nitric oxide (NO), Premature ventricular contraction (PVC), QT prolongation, Ventricular tachycardia (VT)",
author = "Sina Tavakoli and Hajrasouliha, {Amir R.} and Pejman Jabehdar-Maralani and Farzad Ebrahimi and Amirreza Solhpour and Hamed Sadeghipour and Mehdi Ghasemi and Dehpour, {Ahmad R.}",
year = "2007",
month = "3",
day = "1",
doi = "10.1016/j.jhep.2006.09.013",
language = "English (US)",
volume = "46",
pages = "432--439",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Reduced susceptibility to epinephrine-induced arrhythmias in cirrhotic rats

T2 - The roles of nitric oxide and endogenous opioid peptides

AU - Tavakoli, Sina

AU - Hajrasouliha, Amir R.

AU - Jabehdar-Maralani, Pejman

AU - Ebrahimi, Farzad

AU - Solhpour, Amirreza

AU - Sadeghipour, Hamed

AU - Ghasemi, Mehdi

AU - Dehpour, Ahmad R.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - Background/Aims: The clinical relevance of QT prolongation, the most widely recognized cardiac electrophysiological abnormality of cirrhosis, is still undefined. The aim of this study is to examine the susceptibility of chronic (4-week) bile duct-ligated rats to epinephrine-induced arrhythmias. The roles of nitric oxide and endogenous opioids were also evaluated. Methods: Sham-operated and cirrhotic rats were treated with daily subcutaneous administrations of normal saline (1 ml/kg/day), l-NAME (a non-selective nitric oxide synthase inhibitor, 3 mg/kg/day), and naltrexone (20 mg/kg/day) during the fourth week after operation. In order to evaluate the effects of acute nitric oxide synthesis inhibition, additional groups of animals were treated by acute intraperitoneal l-NAME injections (3 mg/kg). Arrhythmias were induced by intravenous injections of 10 μg/kg epinephrine. Results: Despite QT prolongation (P < 0.001), epinephrine induced fewer arrhythmias in cirrhotic rats compared to sham-operated animals (P < 0.05). Chronic, but not acute, l-NAME administration corrected the QT prolongation in cirrhotic rats (P < 0.001), and restored the susceptibility of cirrhotic rats to arrhythmias (P < 0.05). Naltrexone injection without a significant effect on epinephrine-induced arrhythmias corrected QT interval in cirrhotic rats (P < 0.001). Conclusions: This study shows that despite QT prolongation, cirrhotic animals are resistant against epinephrine-induced arrhythmias. This resistance is mediated by chronic nitric oxide overproduction.

AB - Background/Aims: The clinical relevance of QT prolongation, the most widely recognized cardiac electrophysiological abnormality of cirrhosis, is still undefined. The aim of this study is to examine the susceptibility of chronic (4-week) bile duct-ligated rats to epinephrine-induced arrhythmias. The roles of nitric oxide and endogenous opioids were also evaluated. Methods: Sham-operated and cirrhotic rats were treated with daily subcutaneous administrations of normal saline (1 ml/kg/day), l-NAME (a non-selective nitric oxide synthase inhibitor, 3 mg/kg/day), and naltrexone (20 mg/kg/day) during the fourth week after operation. In order to evaluate the effects of acute nitric oxide synthesis inhibition, additional groups of animals were treated by acute intraperitoneal l-NAME injections (3 mg/kg). Arrhythmias were induced by intravenous injections of 10 μg/kg epinephrine. Results: Despite QT prolongation (P < 0.001), epinephrine induced fewer arrhythmias in cirrhotic rats compared to sham-operated animals (P < 0.05). Chronic, but not acute, l-NAME administration corrected the QT prolongation in cirrhotic rats (P < 0.001), and restored the susceptibility of cirrhotic rats to arrhythmias (P < 0.05). Naltrexone injection without a significant effect on epinephrine-induced arrhythmias corrected QT interval in cirrhotic rats (P < 0.001). Conclusions: This study shows that despite QT prolongation, cirrhotic animals are resistant against epinephrine-induced arrhythmias. This resistance is mediated by chronic nitric oxide overproduction.

KW - Bile duct-ligation

KW - Cirrhosis

KW - Endogenous opioid peptides

KW - Epinephrine-induced arrhythmias

KW - Nitric oxide (NO)

KW - Premature ventricular contraction (PVC)

KW - QT prolongation

KW - Ventricular tachycardia (VT)

UR - http://www.scopus.com/inward/record.url?scp=33846636380&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846636380&partnerID=8YFLogxK

U2 - 10.1016/j.jhep.2006.09.013

DO - 10.1016/j.jhep.2006.09.013

M3 - Article

C2 - 17125877

AN - SCOPUS:33846636380

VL - 46

SP - 432

EP - 439

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 3

ER -