Involvement of α2-adrenoceptors in the cardiovascular effects of moxonidine

Abstract

The central sympathoinhibition caused by moxonidine has been explained by activation of α 2-adrenoceptors on the one hand, and by an action at imidazoline I 1 receptors on the other hand. In order to examine these possibilities, effects of moxonidine were compared with those of 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304), an α 2-adrenoceptor agonist with very low affinity for I 1 receptors, in conscious rabbits. The interaction with yohimbine, an α 2-adrenoceptor antagonist with very low affinity for imidazoline I 1 receptors, was also studied. Moxonidine 3–100 μg kg −1 and UK 14304 1–30 μg kg −1 i.v. elicited similar effects: they decreased arterial blood pressure after a transient increase, decreased renal sympathetic nerve activity (recorded with chronically implanted electrodes), decreased heart rate and decreased the plasma noradrenaline concentration. Yohimbine given i.v. antagonized the effects of moxonidine and of UK 14304 in a similar manner. Yohimbine injected into the cisterna magna (i.c.) prevented the hypotension but did not change the decrease in plasma noradrenaline and heart rate, again in the case of both moxonidine and UK 14304. The agreement of the effect patterns of moxonidine and UK 14304, and the similar antagonism of yohimbine against either drug, demonstrate involvement of α 2-adrenoceptors in their central sympathoinhibitory action. The resistance of the bradycardia and the plasma noradrenaline fall against yohimbine i.c. indicates a contribution of presynaptic α 2-adrenergic inhibition of transmitter release from postganglionic sympathetic neurons to the overall reduction of sympathetic tone.