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 language | English (US) |
|---|---|
| Pages (from-to) | 148-153 |
| Number of pages | 6 |
| Journal | European Journal of Pharmacology |
| Volume | 542 |
| Issue number | 1-3 |
| DOIs | |
| State | Published - Aug 7 2006 |
| Externally published | Yes |
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Keywords
- (Rat)
- Adrenergic hyporesponsiveness
- Bile duct ligation
- Cholestasis
- Clonidine
- Endogenous opioids
- Nitric oxide
ASJC Scopus subject areas
- Pharmacology
Cite this
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 journal › Article
}
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
VL - 542
SP - 148
EP - 153
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -