Modulated hemodynamic response to clonidine in bile duct-ligated rats: The role of nitric oxide

Sina Tavakoli, Amir R. Hajrasouliha, Pejman Jabehdar-Maralani, Farzad Ebrahimi, Hamed Sadeghipour, Mehdi Dehghani, Hamed Shafaroodi, Ahmad Reza Dehpour

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Despite the well-known involvement of the peripheral sympathetic abnormalities in the development of cardiovascular complications of cholestasis, the role of the central sympathetic system is still elusive. The goal of this study was to evaluate the effects of central sympathetic tone reduction, through clonidine administration, on hemodynamic parameters of 7-day bile duct-ligated rats. The contributions of nitric oxide and endogenous opioids were also examined by acute intravenous (10 min before clonidine) or chronic daily subcutaneous administrations of N(ω)-nitro-l-arginine methyl ester (l-NAME, 3 mg/kg) or naltrexone (20 mg/kg). Seven days after bile duct ligation or sham operation, animals were anesthetized with sodium pentobarbital. After hemodynamic stabilization, clonidine (10 μg/kg) was injected intravenously, which elicited an initial hypertension (the peripheral effect) followed by persistent hypotension and bradycardia (the central effects). Cholestatic rats demonstrated significant basal bradycardia (P < 0.001) and hypotension (P < 0.05), which were corrected by chronic naltrexone but not l-NAME treatment. While the peripheral effect of clonidine was blunted, the central effects were exaggerated in cholestatic rats (P < 0.01). Acute l-NAME treatment accentuated the hypertensive phase in sham-operated and cholestatic rats (P < 0.05). However, the difference between the two groups was preserved (P < 0.01). This treatment attenuated the central effects in both sham-operated and cholestatic rats to the same level (P < 0.001). Chronic l-NAME treatment resulted in exaggeration of the peripheral response in cholestatic and central responses in sham-operated rats (P < 0.05), and abolished the difference between the groups. Naltrexone treatment had no significant effect on either the central or the peripheral responses to clonidine. This study shows that both central and peripheral hemodynamic responses to clonidine are altered in cholestasis. It also provides evidence that nitric oxide contributes to the development of these abnormalities.

Original languageEnglish (US)
Pages (from-to)148-153
Number of pages6
JournalEuropean Journal of Pharmacology
Volume542
Issue number1-3
DOIs
StatePublished - Aug 7 2006
Externally publishedYes

Fingerprint

Clonidine
Bile Ducts
Nitric Oxide
Hemodynamics
Naltrexone
Cholestasis
Bradycardia
Hypotension
Pentobarbital
Opioid Analgesics
Ligation
Hypertension

Keywords

  • (Rat)
  • Adrenergic hyporesponsiveness
  • Bile duct ligation
  • Cholestasis
  • Clonidine
  • Endogenous opioids
  • Nitric oxide

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tavakoli, S., Hajrasouliha, A. R., Jabehdar-Maralani, P., Ebrahimi, F., Sadeghipour, H., Dehghani, M., ... Dehpour, A. R. (2006). Modulated hemodynamic response to clonidine in bile duct-ligated rats: The role of nitric oxide. European Journal of Pharmacology, 542(1-3), 148-153. https://doi.org/10.1016/j.ejphar.2006.04.052

Modulated hemodynamic response to clonidine in bile duct-ligated rats : The role of nitric oxide. / Tavakoli, Sina; Hajrasouliha, Amir R.; Jabehdar-Maralani, Pejman; Ebrahimi, Farzad; Sadeghipour, Hamed; Dehghani, Mehdi; Shafaroodi, Hamed; Dehpour, Ahmad Reza.

In: European Journal of Pharmacology, Vol. 542, No. 1-3, 07.08.2006, p. 148-153.

Research output: Contribution to journalArticle

Tavakoli, S, Hajrasouliha, AR, Jabehdar-Maralani, P, Ebrahimi, F, Sadeghipour, H, Dehghani, M, Shafaroodi, H & Dehpour, AR 2006, 'Modulated hemodynamic response to clonidine in bile duct-ligated rats: The role of nitric oxide', European Journal of Pharmacology, vol. 542, no. 1-3, pp. 148-153. https://doi.org/10.1016/j.ejphar.2006.04.052
Tavakoli, Sina ; Hajrasouliha, Amir R. ; Jabehdar-Maralani, Pejman ; Ebrahimi, Farzad ; Sadeghipour, Hamed ; Dehghani, Mehdi ; Shafaroodi, Hamed ; Dehpour, Ahmad Reza. / Modulated hemodynamic response to clonidine in bile duct-ligated rats : The role of nitric oxide. In: European Journal of Pharmacology. 2006 ; Vol. 542, No. 1-3. pp. 148-153.
@article{d902502109ad43c2a2ea1cf1da734efd,
title = "Modulated hemodynamic response to clonidine in bile duct-ligated rats: The role of nitric oxide",
abstract = "Despite the well-known involvement of the peripheral sympathetic abnormalities in the development of cardiovascular complications of cholestasis, the role of the central sympathetic system is still elusive. The goal of this study was to evaluate the effects of central sympathetic tone reduction, through clonidine administration, on hemodynamic parameters of 7-day bile duct-ligated rats. The contributions of nitric oxide and endogenous opioids were also examined by acute intravenous (10 min before clonidine) or chronic daily subcutaneous administrations of N(ω)-nitro-l-arginine methyl ester (l-NAME, 3 mg/kg) or naltrexone (20 mg/kg). Seven days after bile duct ligation or sham operation, animals were anesthetized with sodium pentobarbital. After hemodynamic stabilization, clonidine (10 μg/kg) was injected intravenously, which elicited an initial hypertension (the peripheral effect) followed by persistent hypotension and bradycardia (the central effects). Cholestatic rats demonstrated significant basal bradycardia (P < 0.001) and hypotension (P < 0.05), which were corrected by chronic naltrexone but not l-NAME treatment. While the peripheral effect of clonidine was blunted, the central effects were exaggerated in cholestatic rats (P < 0.01). Acute l-NAME treatment accentuated the hypertensive phase in sham-operated and cholestatic rats (P < 0.05). However, the difference between the two groups was preserved (P < 0.01). This treatment attenuated the central effects in both sham-operated and cholestatic rats to the same level (P < 0.001). Chronic l-NAME treatment resulted in exaggeration of the peripheral response in cholestatic and central responses in sham-operated rats (P < 0.05), and abolished the difference between the groups. Naltrexone treatment had no significant effect on either the central or the peripheral responses to clonidine. This study shows that both central and peripheral hemodynamic responses to clonidine are altered in cholestasis. It also provides evidence that nitric oxide contributes to the development of these abnormalities.",
keywords = "(Rat), Adrenergic hyporesponsiveness, Bile duct ligation, Cholestasis, Clonidine, Endogenous opioids, Nitric oxide",
author = "Sina Tavakoli and Hajrasouliha, {Amir R.} and Pejman Jabehdar-Maralani and Farzad Ebrahimi and Hamed Sadeghipour and Mehdi Dehghani and Hamed Shafaroodi and Dehpour, {Ahmad Reza}",
year = "2006",
month = "8",
day = "7",
doi = "10.1016/j.ejphar.2006.04.052",
language = "English (US)",
volume = "542",
pages = "148--153",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - Modulated hemodynamic response to clonidine in bile duct-ligated rats

T2 - The role of nitric oxide

AU - Tavakoli, Sina

AU - Hajrasouliha, Amir R.

AU - Jabehdar-Maralani, Pejman

AU - Ebrahimi, Farzad

AU - Sadeghipour, Hamed

AU - Dehghani, Mehdi

AU - Shafaroodi, Hamed

AU - Dehpour, Ahmad Reza

PY - 2006/8/7

Y1 - 2006/8/7

N2 - Despite the well-known involvement of the peripheral sympathetic abnormalities in the development of cardiovascular complications of cholestasis, the role of the central sympathetic system is still elusive. The goal of this study was to evaluate the effects of central sympathetic tone reduction, through clonidine administration, on hemodynamic parameters of 7-day bile duct-ligated rats. The contributions of nitric oxide and endogenous opioids were also examined by acute intravenous (10 min before clonidine) or chronic daily subcutaneous administrations of N(ω)-nitro-l-arginine methyl ester (l-NAME, 3 mg/kg) or naltrexone (20 mg/kg). Seven days after bile duct ligation or sham operation, animals were anesthetized with sodium pentobarbital. After hemodynamic stabilization, clonidine (10 μg/kg) was injected intravenously, which elicited an initial hypertension (the peripheral effect) followed by persistent hypotension and bradycardia (the central effects). Cholestatic rats demonstrated significant basal bradycardia (P < 0.001) and hypotension (P < 0.05), which were corrected by chronic naltrexone but not l-NAME treatment. While the peripheral effect of clonidine was blunted, the central effects were exaggerated in cholestatic rats (P < 0.01). Acute l-NAME treatment accentuated the hypertensive phase in sham-operated and cholestatic rats (P < 0.05). However, the difference between the two groups was preserved (P < 0.01). This treatment attenuated the central effects in both sham-operated and cholestatic rats to the same level (P < 0.001). Chronic l-NAME treatment resulted in exaggeration of the peripheral response in cholestatic and central responses in sham-operated rats (P < 0.05), and abolished the difference between the groups. Naltrexone treatment had no significant effect on either the central or the peripheral responses to clonidine. This study shows that both central and peripheral hemodynamic responses to clonidine are altered in cholestasis. It also provides evidence that nitric oxide contributes to the development of these abnormalities.

AB - Despite the well-known involvement of the peripheral sympathetic abnormalities in the development of cardiovascular complications of cholestasis, the role of the central sympathetic system is still elusive. The goal of this study was to evaluate the effects of central sympathetic tone reduction, through clonidine administration, on hemodynamic parameters of 7-day bile duct-ligated rats. The contributions of nitric oxide and endogenous opioids were also examined by acute intravenous (10 min before clonidine) or chronic daily subcutaneous administrations of N(ω)-nitro-l-arginine methyl ester (l-NAME, 3 mg/kg) or naltrexone (20 mg/kg). Seven days after bile duct ligation or sham operation, animals were anesthetized with sodium pentobarbital. After hemodynamic stabilization, clonidine (10 μg/kg) was injected intravenously, which elicited an initial hypertension (the peripheral effect) followed by persistent hypotension and bradycardia (the central effects). Cholestatic rats demonstrated significant basal bradycardia (P < 0.001) and hypotension (P < 0.05), which were corrected by chronic naltrexone but not l-NAME treatment. While the peripheral effect of clonidine was blunted, the central effects were exaggerated in cholestatic rats (P < 0.01). Acute l-NAME treatment accentuated the hypertensive phase in sham-operated and cholestatic rats (P < 0.05). However, the difference between the two groups was preserved (P < 0.01). This treatment attenuated the central effects in both sham-operated and cholestatic rats to the same level (P < 0.001). Chronic l-NAME treatment resulted in exaggeration of the peripheral response in cholestatic and central responses in sham-operated rats (P < 0.05), and abolished the difference between the groups. Naltrexone treatment had no significant effect on either the central or the peripheral responses to clonidine. This study shows that both central and peripheral hemodynamic responses to clonidine are altered in cholestasis. It also provides evidence that nitric oxide contributes to the development of these abnormalities.

KW - (Rat)

KW - Adrenergic hyporesponsiveness

KW - Bile duct ligation

KW - Cholestasis

KW - Clonidine

KW - Endogenous opioids

KW - Nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=33745991129&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745991129&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2006.04.052

DO - 10.1016/j.ejphar.2006.04.052

M3 - Article

C2 - 16824510

AN - SCOPUS:33745991129

VL - 542

SP - 148

EP - 153

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3

ER -