Evidence for the involvement of imidazoline receptors in the central hypotensive effect of rilmenidine in the rabbit.

1. Rilmenidine has recently been introduced as a new centrally-acting antihypertensive agent. We examined its cardiovascular effects after intracerebral injection to anaesthetized rabbits. Cumulative doses of rilmenidine injected intracisternally (1 to 300 micrograms kg-1) led to dose-dependent decreases in arterial blood pressure and heart rate. The effective doses of rilmenidine were lower when injected centrally than when injected intravenously. 2. Pretreatment with the same dose of yohimbine or idazoxan shifted the rilmenidine dose-response curves for its hypotensive and bradycardic effects to the right. Idazoxan, which has an imidazoline structure, proved to be a more active antagonist than yohimbine of rilmenidine centrally-mediated cardiovascular effects. 3. The dose-response curve for the central hypotensive effect of rilmenidine was also shifted to the right after pretreatment with a bovine brain extract. This extract contains the endogenous ligand of the imidazoline-preferring receptors which is not a catecholamine. 4. Rilmenidine, like clonidine, proved to be active when micro-injected into the rabbit nucleus reticularis lateralis region. 5. In conclusion, rilmenidine exhibited in the rabbit a central hypotensive effect which originated in the same area as where clonidine acts. Specific imidazoline-preferring receptors appear to be involved in this hypotensive effect.