Contribution of alpha 2-adrenoceptors to the central cardiovascular effects of clonidine and S 8350 in anaesthetized rats.

Abstract

1. The alpha 2-adrenoceptor agonist clonidine elicits centrally mediated effects through an interaction with both alpha 2-adrenoceptors and imidazoline binding sites. 2. We selected a new oxazoline derivative, S 8350, which competes with [3H]-yohimbine for binding to cerebral alpha 2-adrenoceptors (IC50, 67 +/= 17 nmol/L) and displays a higher affinity (35-fold) for alpha 2- than for alpha 1-adrenoceptors. 3. As observed for clonidine, intravenous (i.v.) administration of S 8350 resulted in a brief pressor effect followed by a prolonged hypotension. When S 8350 was administered i.v. to spinally pithed rats, only a rise in blood pressure was observed. 4. In order to discriminate the cardiovascular effects related to the central imidazoline receptor or alpha 2-adrenoceptor activation, the effects of intracisternal (i.c.) administration of clonidine and S 8350 were investigated in the rat. 5. In the anaesthetized rat, both clonidine and S 8350 displayed a profound central (i.c. route) hypotensive effect associated with a bradycardia. 6. The cardiovascular effects of S 8350 were abolished by the central administration of the selective alpha 2-adrenoceptor antagonist rauwolscine. Conversely, rauwolscine completely prevented bradycardia but it induced only a partial reversion of the hypotension elicited by clonidine. 7. These results suggest that central alpha 2-adrenoceptors are responsible for hypotension and bradycardia while imidazoline binding sites do not apparently contribute to heart rate control.

• Authors: V Deckert, V Lachaud, A Parini, J L Elghozi
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 18 Issue 10 Pg. 401-8 (Oct 1991) ISSN: 0305-1870 [Print] Australia
• PMID: 1684919 (Publication Type: Comparative Study, Corrected and Republished Article, Journal Article)

Chemical References

• Adrenergic alpha-Agonists
• Adrenergic alpha-Antagonists
• Oxazoles
• Receptors, Adrenergic, alpha
• Yohimbine
• 2-((1-cyclohexyl-2,2,2-trifluoro)ethylamino)oxazoline
• Clonidine

Topics

• Adrenergic alpha-Agonists (metabolism, pharmacology)
• Adrenergic alpha-Antagonists (metabolism, pharmacology)
• Animals
• Binding, Competitive
• Blood Pressure (drug effects)
• Cardiovascular System (drug effects)
• Cerebral Cortex (metabolism, ultrastructure)
• Clonidine (pharmacology)
• Heart Rate (drug effects)
• Male
• Oxazoles (pharmacology)
• Rats
• Receptors, Adrenergic, alpha (drug effects, metabolism, physiology)
• Yohimbine (metabolism, pharmacology)