alpha(2)-adrenergic receptors are not required for central anti-hypertensive action of moxonidine in mice

In the mouse medulla oblongata, we characterized binding properties and fun ctional responses of two recognition sites for imidazoline compounds: I-1-i midazoline and alpha(2)-adrenergic receptors. The mouse medulla expresses a higher density of I-1-receptors than in the rat, whereas alpha(2)-receptor densities were similar between the two species. In anesthetized, ventilate d and paralyzed mice, we tested the hypotensive actions of the I-1/alpha(2) agonist moxonidine, determined its central site of its actions, and the re lative roles of I-1 and alpha(2)-receptors. Experiments were performed in C (57)Bl(6) wild type and alpha(2A)-adrenergic receptor deficient mice. In bo th types of mice, neuronal activation within the rostral ventrolateral medu lla (RVLM) region by glutamate microinjection elicited increases in arteria l pressure. Moxonidine (0.5 nmol/site/10 nl) microinjected bilaterally into this vasopressor region decreased arterial pressure by 30% and heart rate by 11% in wild type mice. Efaroxan, the I-1/alpha(2) antagonist (0.4 nmol) when microinjected into the RVLM elevated blood pressure itself and abolish ed the action of moxonidine, whereas alpha(2)-blockade with SK&F 86466 had no significant effect on blood pressure and did not attenuate moxonidine's effect. To more definitively test the role of alpha(2)-adrenergic receptors in the action of moxonidine, moxonidine was microinjected into the RVLM of alpha(2A)-adrenergic deficient mice. The decreases in arterial pressure we re nearly identical to those of wild type mice, whereas bradycardia was att enuated. Thus, in the mouse moxonidine acts within the RVLM region to lower arterial pressure mainly through the I-1-imidazoline receptor independent of alpha(2)-adrenergic receptors. (C) 2000 Published by Elsevier Science B. V. All rights reserved.