I-1 imidazoline receptors in cardiovascular regulation: The place of rilmenidine

From the very earliest suggestion of a distinction between imidazoline rece ptors and a,adrenoceptors, there has been much debate as to their contribut ion to the antihypertensive actions of clonidine-like agents. However, with the development of drugs such as rilmenidine that are more selective for I , imidazoline receptors, their role and also their close relationship with a,adrenoceptors has become clearer. We have examined this question using a range of imidazoline and alpha(2)-adrenoceptor antagonists given centrally and peripherally to conscious rabbits. We found that second-generation agen ts such as rilmenidine preferentially act via imidazoline receptors but tha t alpha(2)-adrenoceptors are important for the hypotension produced by the first-generation agents clonidine and a-methyldopa. In addition to the hypo tension, rilmenidine facilitates cardiac vagal baroreflexes and inhibits ca rdiac sympathetic baroreflexes and diminishes the increase in renal sympath etic activity produced by environmental stress. In other studies using anes thetized rabbits and direct measures of sympathetic nerve activity, we conf irmed that the major site of sympathoinhibitory actions and sympathetic bar oreflex effects of rilmenidine is the rostral ventrolateral medulla. Our re sults also suggest that alpha(2)-adrenoceptors are activated as a consequen ce of imidazoline receptor activation by rilmenidine. Thus, though imidazol ine receptors appear to be the primary target of rilmenidine, "downstream" alpha(2)-adrenoceptors within the brainstem are also involved and need to b e considered in developing pharmacologic strategies for antihypertensive tr eatment involving imidazoline agents. (C) 2000 American Journal of Hyperten sion, Ltd.