CONTRIBUTION OF α2‐ADRENOCEPTORS TO THE CENTRAL CARDIOVASCULAR EFFECTS OF CLONIDINE AND S 8350 IN ANAESTHETIZED RATS

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Abstract
SUMMARY: 1. The α2‐adrenoceptor agonist clonidine elicits centrally mediated effects through an interaction with both α2‐adrenoceptors and imidazoline binding sites.2. We selected a new oxazoline derivative, S 8350, which competes with [3H]‐yohimbine for binding to cerebral α2‐adrenoceptors (IC50, 67 ± 17 nmol/L) and displays a higher affinity (35‐fold) for α2‐ than for α1‐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 α2‐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 α2‐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 α2‐adrenoceptors are responsible for hypotension and bradycardia while imidazoline binding sites do not apparently contribute to heart rate control.