Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to β-adrenergic stimulation in cirrhotic rats

Farzad Ebrahimi, Sina Tavakoli, Amir R. Hajrasouliha, Hamed Sadeghipour, Mehdi Dehghani, Seyed Hossein Ahmadi, Ahmad Reza Dehpour

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

It is well known that chronotropic and inotropic responses to β-adrenergic stimulation are impaired in cirrhosis, but the exact reason is not clear. Considering the inhibitory effect of endogenous opioid peptides and nitric oxide (NO) on β-adrenergic pathway, we examined their roles in hyporesponsiveness of isolated atria and papillary muscles to isoproterenol stimulation in cirrhotic rats. Cirrhosis was induced by chronic bile duct ligation. Four weeks after ligation or sham operation, the responses of the isolated atria and papillary muscles to isoproterenol stimulation were evaluated in the absence and presence of naltrexone HCl (10 -6 m), N(ω)-nitro-l-arginine methyl ester (l-NAME, 10 -4 m), and naltrexone plus l-NAME in the organ bath. Considering the role of inducible NOS (iNOS) in hemodynamic abnormalities of cirrhotic rats, the chronotropic and inotropic responses of cirrhotic rats to isoproterenol stimulation were also assessed in the presence of aminoguanidine (a selective inhibitor of iNOS, 3 × 10 -4 m). Sham operation had no significant effect on basal atrial beating rate, contractile force, and maximal time derivatives for the development and the dissipation of papillary muscle tension. The basal atrial beating rate of cirrhotic rats did not show any significant difference compared with the sham-operated ones; however, the basal contractile parameters were significantly decreased in cirrhosis. Although the maximum effects of isoproterenol on chronotropic and inotropic responses were significantly reduced in cirrhotic rats, there was no difference in half-maximal effective concentrations of isoproterenol in these concentration-response curves. The basal abnormalities and the attenuated chronotropic and inotropic responses to isoproterenol were completely corrected by the administration of naltrexone, l-NAME and aminoguanidine. Concurrent administration of naltrexone and l-NAME also restored to normal the basal abnormalities and the blunted responses to isoproterenol in cirrhotic rats, and did not show any antagonistic effect. Based on these findings, both the endogenous opioid peptides and NO may be involved in the attenuated chronotropic and inotropic responses to β-adrenergic stimulation in cirrhosis. It seems that the iNOS activity results in NO-induced hyporesponsiveness to β-adrenergic stimulation in cirrhosis.

Original languageEnglish (US)
Pages (from-to)461-471
Number of pages11
JournalFundamental and Clinical Pharmacology
Volume20
Issue number5
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

Fingerprint

Opioid Peptides
Isoproterenol
Adrenergic Agents
Nitric Oxide
Naltrexone
Fibrosis
Papillary Muscles
Ligation
Muscle Tonus
Bile Ducts
Baths
Hemodynamics

Keywords

  • β-adrenergic receptor
  • Bile duct ligation
  • Cardiomyopathy
  • Cirrhosis
  • Endogenous opioid peptides
  • Nitric oxide

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to β-adrenergic stimulation in cirrhotic rats. / Ebrahimi, Farzad; Tavakoli, Sina; Hajrasouliha, Amir R.; Sadeghipour, Hamed; Dehghani, Mehdi; Ahmadi, Seyed Hossein; Dehpour, Ahmad Reza.

In: Fundamental and Clinical Pharmacology, Vol. 20, No. 5, 01.10.2006, p. 461-471.

Research output: Contribution to journalArticle

Ebrahimi, Farzad ; Tavakoli, Sina ; Hajrasouliha, Amir R. ; Sadeghipour, Hamed ; Dehghani, Mehdi ; Ahmadi, Seyed Hossein ; Dehpour, Ahmad Reza. / Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to β-adrenergic stimulation in cirrhotic rats. In: Fundamental and Clinical Pharmacology. 2006 ; Vol. 20, No. 5. pp. 461-471.
@article{39fdda8e2eed4023829aa418e237bc22,
title = "Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to β-adrenergic stimulation in cirrhotic rats",
abstract = "It is well known that chronotropic and inotropic responses to β-adrenergic stimulation are impaired in cirrhosis, but the exact reason is not clear. Considering the inhibitory effect of endogenous opioid peptides and nitric oxide (NO) on β-adrenergic pathway, we examined their roles in hyporesponsiveness of isolated atria and papillary muscles to isoproterenol stimulation in cirrhotic rats. Cirrhosis was induced by chronic bile duct ligation. Four weeks after ligation or sham operation, the responses of the isolated atria and papillary muscles to isoproterenol stimulation were evaluated in the absence and presence of naltrexone HCl (10 -6 m), N(ω)-nitro-l-arginine methyl ester (l-NAME, 10 -4 m), and naltrexone plus l-NAME in the organ bath. Considering the role of inducible NOS (iNOS) in hemodynamic abnormalities of cirrhotic rats, the chronotropic and inotropic responses of cirrhotic rats to isoproterenol stimulation were also assessed in the presence of aminoguanidine (a selective inhibitor of iNOS, 3 × 10 -4 m). Sham operation had no significant effect on basal atrial beating rate, contractile force, and maximal time derivatives for the development and the dissipation of papillary muscle tension. The basal atrial beating rate of cirrhotic rats did not show any significant difference compared with the sham-operated ones; however, the basal contractile parameters were significantly decreased in cirrhosis. Although the maximum effects of isoproterenol on chronotropic and inotropic responses were significantly reduced in cirrhotic rats, there was no difference in half-maximal effective concentrations of isoproterenol in these concentration-response curves. The basal abnormalities and the attenuated chronotropic and inotropic responses to isoproterenol were completely corrected by the administration of naltrexone, l-NAME and aminoguanidine. Concurrent administration of naltrexone and l-NAME also restored to normal the basal abnormalities and the blunted responses to isoproterenol in cirrhotic rats, and did not show any antagonistic effect. Based on these findings, both the endogenous opioid peptides and NO may be involved in the attenuated chronotropic and inotropic responses to β-adrenergic stimulation in cirrhosis. It seems that the iNOS activity results in NO-induced hyporesponsiveness to β-adrenergic stimulation in cirrhosis.",
keywords = "β-adrenergic receptor, Bile duct ligation, Cardiomyopathy, Cirrhosis, Endogenous opioid peptides, Nitric oxide",
author = "Farzad Ebrahimi and Sina Tavakoli and Hajrasouliha, {Amir R.} and Hamed Sadeghipour and Mehdi Dehghani and Ahmadi, {Seyed Hossein} and Dehpour, {Ahmad Reza}",
year = "2006",
month = "10",
day = "1",
doi = "10.1111/j.1472-8206.2006.00431.x",
language = "English (US)",
volume = "20",
pages = "461--471",
journal = "Fundamental and Clinical Pharmacology",
issn = "0767-3981",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to β-adrenergic stimulation in cirrhotic rats

AU - Ebrahimi, Farzad

AU - Tavakoli, Sina

AU - Hajrasouliha, Amir R.

AU - Sadeghipour, Hamed

AU - Dehghani, Mehdi

AU - Ahmadi, Seyed Hossein

AU - Dehpour, Ahmad Reza

PY - 2006/10/1

Y1 - 2006/10/1

N2 - It is well known that chronotropic and inotropic responses to β-adrenergic stimulation are impaired in cirrhosis, but the exact reason is not clear. Considering the inhibitory effect of endogenous opioid peptides and nitric oxide (NO) on β-adrenergic pathway, we examined their roles in hyporesponsiveness of isolated atria and papillary muscles to isoproterenol stimulation in cirrhotic rats. Cirrhosis was induced by chronic bile duct ligation. Four weeks after ligation or sham operation, the responses of the isolated atria and papillary muscles to isoproterenol stimulation were evaluated in the absence and presence of naltrexone HCl (10 -6 m), N(ω)-nitro-l-arginine methyl ester (l-NAME, 10 -4 m), and naltrexone plus l-NAME in the organ bath. Considering the role of inducible NOS (iNOS) in hemodynamic abnormalities of cirrhotic rats, the chronotropic and inotropic responses of cirrhotic rats to isoproterenol stimulation were also assessed in the presence of aminoguanidine (a selective inhibitor of iNOS, 3 × 10 -4 m). Sham operation had no significant effect on basal atrial beating rate, contractile force, and maximal time derivatives for the development and the dissipation of papillary muscle tension. The basal atrial beating rate of cirrhotic rats did not show any significant difference compared with the sham-operated ones; however, the basal contractile parameters were significantly decreased in cirrhosis. Although the maximum effects of isoproterenol on chronotropic and inotropic responses were significantly reduced in cirrhotic rats, there was no difference in half-maximal effective concentrations of isoproterenol in these concentration-response curves. The basal abnormalities and the attenuated chronotropic and inotropic responses to isoproterenol were completely corrected by the administration of naltrexone, l-NAME and aminoguanidine. Concurrent administration of naltrexone and l-NAME also restored to normal the basal abnormalities and the blunted responses to isoproterenol in cirrhotic rats, and did not show any antagonistic effect. Based on these findings, both the endogenous opioid peptides and NO may be involved in the attenuated chronotropic and inotropic responses to β-adrenergic stimulation in cirrhosis. It seems that the iNOS activity results in NO-induced hyporesponsiveness to β-adrenergic stimulation in cirrhosis.

AB - It is well known that chronotropic and inotropic responses to β-adrenergic stimulation are impaired in cirrhosis, but the exact reason is not clear. Considering the inhibitory effect of endogenous opioid peptides and nitric oxide (NO) on β-adrenergic pathway, we examined their roles in hyporesponsiveness of isolated atria and papillary muscles to isoproterenol stimulation in cirrhotic rats. Cirrhosis was induced by chronic bile duct ligation. Four weeks after ligation or sham operation, the responses of the isolated atria and papillary muscles to isoproterenol stimulation were evaluated in the absence and presence of naltrexone HCl (10 -6 m), N(ω)-nitro-l-arginine methyl ester (l-NAME, 10 -4 m), and naltrexone plus l-NAME in the organ bath. Considering the role of inducible NOS (iNOS) in hemodynamic abnormalities of cirrhotic rats, the chronotropic and inotropic responses of cirrhotic rats to isoproterenol stimulation were also assessed in the presence of aminoguanidine (a selective inhibitor of iNOS, 3 × 10 -4 m). Sham operation had no significant effect on basal atrial beating rate, contractile force, and maximal time derivatives for the development and the dissipation of papillary muscle tension. The basal atrial beating rate of cirrhotic rats did not show any significant difference compared with the sham-operated ones; however, the basal contractile parameters were significantly decreased in cirrhosis. Although the maximum effects of isoproterenol on chronotropic and inotropic responses were significantly reduced in cirrhotic rats, there was no difference in half-maximal effective concentrations of isoproterenol in these concentration-response curves. The basal abnormalities and the attenuated chronotropic and inotropic responses to isoproterenol were completely corrected by the administration of naltrexone, l-NAME and aminoguanidine. Concurrent administration of naltrexone and l-NAME also restored to normal the basal abnormalities and the blunted responses to isoproterenol in cirrhotic rats, and did not show any antagonistic effect. Based on these findings, both the endogenous opioid peptides and NO may be involved in the attenuated chronotropic and inotropic responses to β-adrenergic stimulation in cirrhosis. It seems that the iNOS activity results in NO-induced hyporesponsiveness to β-adrenergic stimulation in cirrhosis.

KW - β-adrenergic receptor

KW - Bile duct ligation

KW - Cardiomyopathy

KW - Cirrhosis

KW - Endogenous opioid peptides

KW - Nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=33748679793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748679793&partnerID=8YFLogxK

U2 - 10.1111/j.1472-8206.2006.00431.x

DO - 10.1111/j.1472-8206.2006.00431.x

M3 - Article

C2 - 16968416

AN - SCOPUS:33748679793

VL - 20

SP - 461

EP - 471

JO - Fundamental and Clinical Pharmacology

JF - Fundamental and Clinical Pharmacology

SN - 0767-3981

IS - 5

ER -