COMPARISON OF THE BARORECEPTOR HEART-RATE REFLEX EFFECTS OF MOXONIDINE, RILMENIDINE AND CLONIDINE IN CONSCIOUS RABBITS

In 10 conscious rabbits, the baroreceptor-heart rate (HR) reflex effec ts of centrally acting antihypertensive agents with high affinity for imidazoline receptors (IRs), moxonidine and rilmenidine, were compared with clonidine which acts predominantly via central alpha(2)-adrenoce ptors. Dose regimens were chosen to give similar hypotension (- 17 +/- 1 mm Hg) and bradycardia (- 27 +/- 2 b/min) for all three agents give n into the fourth ventricle. Baroreceptor-HR reflex curves were assess ed by i.v. drug induced changes in blood pressure. With all treatments , the baroreflex curves with both vagal and sympathetic effecters inta ct were shifted to the left, corresponding to the hypotension, and the bradycardia plateau was reduced. Rilmenidine and moxonidine also redu ced the upper plateau such that the curves were shifted parallel down the HR scale with no change in the HR range. By contrast, clonidine on ly decreased the lower plateau, and thus increased HR range (+19 +/- 6 %). Moxonidine, but not rilmenidine, reduced the baroreflex gain by re ducing the curvature. Clonidine also decreased curvature but this did not result in a reduction in gain as it was offset by the increase in HR range. The gain and range of the cardiac sympathetic component, as assessed after vagal blockade, was reduced by rilmenidine by 53 and 40 % respectively, but was not affected by the other agents. The calculat ed vagal component of the curves showed that all agents produced a gre ater vagal bradycardia in response to a rise in pressure and that both rilmenidine and clonidine increased vagal HR range. The present study results show that many of the baroreflex effects of clonidine, such a s facilitating cardiac vagal responses, are shared by the second gener ation agent rilmenidine, suggesting that they are primarily due to alp ha(2)-adrenoceptor activation. In addition, the inhibition of the symp athetic component of the baroreflex, observed with rilmenidine, and no t clonidine suggests that this effect may involve IRs. By contrast mox onidine, the most specific agent for I, receptors, produces mainly a b aroreflex independent inhibition of cardiac sympathetic activity with little effect on vagal activity. (C) 1998 Elsevier Science B.V. All ri ghts reserved.