Chronic I-1-imidazoline agonism sympathetic mechanisms in hypertension

Evidence exists for a state of sympathetic hyperactivity in essential hyper tension, and moxonidine, a new central sympathetic inhibitor, has been intr oduced for its treatment. Acute administration of moxonidine lowers periphe ral sympathetic neural output. This study examined the effect of chronic mo xonidine therapy, at increasing therapeutic doses, on resting peripheral sy mpathetic activity and vascular resistance and their responses to physiolog ical reflex maneuvers. Twelve newly diagnosed patients with essential hyper tension were studied sequentially at least 1 month apart, initially on no t herapy, then on 200 mu g, and finally on 400 mu g of oral moxonidine daily. Changes in heart rate, arterial blood pressure, calf vascular resistance, and peripheral sympathetic drive were assessed at rest and during reflex ma neuvers. Peroneal microneurography was used to quantify peripheral sympathe tic vasoconstrictor activity by single-unit and multiunit techniques. Moxon idine therapy progressively reduced resting mean arterial pressure (P<0.000 1) without affecting heart rate. At 200 mu g daily, there was a significant reduction in sympathetic nerve activity (P<0.001) and calf vascular resist ance (P<0.01). At 400 mu g daily, further reductions were smaller and insig nificant. Responses to cold stimulus and isometric handgrip exercise showed a similar pattern, with the greatest magnitude of change at 200 mu g daily , In patients with essential hypertension, chronic moxonidine therapy inhib ited resting sympathetic vasoconstrictor drive and also its reflex response s, The magnitude of inhibition became less as the therapeutic dose was incr eased, suggesting that moxonidine may be more effective under conditions of high sympathetic activity.