Role of imidazoline receptors in the cardiovascular actions of moxonidine, rilmenidine and clonidine in conscious rabbits

Abstract

The present study in conscious rabbits with intracisternal (i.c.) catheters sought to determine the relative contribution of the I1 subtype of imidazoline receptors (IR) and alpha2 adrenoceptors to the hypotensive effects of rilmenidine, clonidine and moxonidine with an I1-IR/alpha2 adrenoceptor antagonist efaroxan and a specific alpha2 adrenoceptor antagonist 2-methoxyidazoxan (2-MI). The alpha2 adrenoceptor antagonist effect of efaroxan was compared with 2-MI by performing cumulative dose-response curves in the presence of α-methyldopa (400 μg/kg i.c.). 2-MI was 5.6 times more potent than efaroxan at reversing 75% of the hypotension elicited by α-methyldopa (P < .01). These findings suggest that rilmenidine and moxonidine act predominantly via IR. By contrast, 2-MI was more effective at reversing the clonidine-induced hypotension than was efaroxan (P < .001), suggesting that clonidine acts mainly via alpha2 adrenoceptors in conscious normotensive rabbits. Thus, a higher selectivity of the second generation agents moxonidine and rilmenidine for I1-IR over alpha2 adrenoceptors, compared with the first generation agent clonidine, appears to be necessary for this effect to be manifested in their hypotensive actions.