Comparison of the baroreceptor–heart rate reflex effects of moxonidine, rilmenidine and clonidine in conscious rabbits

Abstract

In 10 conscious rabbits, the baroreceptor–heart rate (HR) reflex effects of centrally acting antihypertensive agents with high affinity for imidazoline receptors (IRs), moxonidine and rilmenidine, were compared with clonidine which acts predominantly via central α 2-adrenoceptors. Dose regimens were chosen to give similar hypotension (−17±1 mm Hg) and bradycardia (−27±2 b/min) for all three agents given into the fourth ventricle. Baroreceptor–HR reflex curves were assessed by i.v. drug induced changes in blood pressure. With all treatments, the baroreflex curves with both vagal and sympathetic effectors intact were shifted to the left, corresponding to the hypotension, and the bradycardia plateau was reduced. Rilmenidine and moxonidine also reduced the upper plateau such that the curves were shifted parallel down the HR scale with no change in the HR range. By contrast, clonidine only decreased the lower plateau, and thus increased HR range (+19±6%). Moxonidine, but not rilmenidine, reduced the baroreflex gain by reducing 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 calculated vagal component of the curves showed that all agents produced a greater 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 as facilitating cardiac vagal responses, are shared by the second generation agent rilmenidine, suggesting that they are primarily due to α 2-adrenoceptor activation. In addition, the inhibition of the sympathetic component of the baroreflex, observed with rilmenidine, and not clonidine suggests that this effect may involve IRs. By contrast moxonidine, the most specific agent for I 1 receptors, produces mainly a baroreflex independent inhibition of cardiac sympathetic activity with little effect on vagal activity.