Central imidazoline receptors and centrally acting anti-hypertensive agents.

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 (i.v.) or into the fourth ventricle (4V) was preferentially reversed by the IR antagonists idazoxan and efaroxan (compared to a selective alpha(2)-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 alpha(2)-adrenoceptors. In anaesthetised rabbits, the rostral ventrolateral medulla (RVLM) was the most potent site for rilmenidine to produce the sympatho-inhibition and modulation of sympathetic baroreflexes. alpha-Methylnoradrenaline was also sympatholytic suggesting alpha(2)-adrenoceptors are also present in this site. Microinjection of the IR and alpha(2)-adrenoceptor antagonists showed that rilmenidine activates IR in the RVLM but that alpha(2)-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 alpha(2)-adrenoceptors and IR in the region.