Central Imidazoline Receptors and Centrally Acting Anti-Hypertensive Agents

Abstract

We have examined the location and contribution of imidazoline receptors (IR) in mediating the hypotensive and sympatholytic actions of first and second generation anti-hypertensive agents in rabbits. We found that the hypotension produced by rilmenidine and moxonidine given intravenously (IV) or into the fourth ventricle (4V) was preferentially reversed by the IR antagonists idazoxan and efaroxan (compared to a selective α₂-adrenoceptor antagonist 2-methoxy-idazoxan), suggesting that IR are important in the sympatho-inhibition produced by these agents. Clonidine was not preferentially reversed by the IR antagonists suggesting an action via aadrenoceptors.In anaesthetised rabbits, the rostral ventrolateral medulla(RVLM) was the most potent site for rilmenidine to produce the sympathoinhibition and modulation of sympathetic baroreflexes. a-Methylnoradrenalhe was also sympatholytic suggesting a-adrenoceptors are also present in this site. Microinjection of the IR and a-adrenoceptor antagonists showed that rilmenidine activates IR in the RVLM but that a-adrenoceptors are also activated as a consequence. These studies suggest that rilmenidine acts primarily via IR in the RVLM to reduce sympathetic tone but also imply an important association of a-adrenoceptors and IR in the region.

Key Words:

• Blood pressure
• Methyldopa
• Clonidine
• Rilmenidine
• Moxonidine α₂-Adrenoceptors
• Imidazoline receptors
• Idazoxan
• Efaroxan
• Renal sympathetic baroreflexes
• Rostral ventrolateral medulla oblongata
• Rabbits