Rilmenidine lowers arterial pressure via imidazole receptors in brainstem C1 area

Abstract

We sought to determine the site of action and receptor type responsible for the antihypertensive actions of rilmenidine. an oxazoline analogue of clonidine. In anesthetized paralyzed rats decerebration did not alter the dose dependent reductions in arterial pressure and heart rate elicited by i.v. drug. Rilmenidine microinjected bilaterally into the C1 area of the rostral ventrolateral medulla (RVL), but not nucleus tractus solitarii (NTS) nor caudal ventrolateral medulla (CVL), elicited dose-dependent falls in arterial pressure and heart rate at doses an order of magnitude less than required systemically. Prior microinjection into the Cl area of the selective α 2-adrenoceptor antagonist SKF-86466, even at high doses, failed to modify the hypotension to i.v. rilmenidine. However, microinjection of 3- to 10-fold lower doses of idazoxan, a ligand for imidazole as well as α 2-adrenoceptors, blocked the effects. Rilmenidine also competed with the clonidine analogue [ 3H]p-aminoclonidine ([ 3H]pac) at specific binding sites in membranes of bovine ventrolateral medulla and frontal cortex. In RVL rilmenidine competed with binding to imidazole and α 2-adrenergic binding sites with a 30-fold selectivity for the imidazole binding sites. In frontal cortex binding was of lower affinity and restricted to α 2-adrenergic sites. We conclude that rilmenidine, like clonidine, acts to lower arterial pressure by an action on imidazole receptors in the Cl area of RVL. The higher selectivity of rilmenidine for imidazole to α 2-adrenoceptors as compared to clonidine may explain the lower sedative effects of rilmenidine. Rilmenidine; Oxazoline; α 2-Adrenoceptors; Imidazole receptors; Medulla (rostral ventrolateral); Arterial pressure