Chronic I(1)-imidazoline agonism : sympathetic mechanisms in hypertension.
Evidence exists for a state of sympathetic hyperactivity in essential hypertension, and moxonidine, a new central sympathetic inhibitor, has been introduced for its treatment. Acute administration of moxonidine lowers peripheral sympathetic neural output. This study examined the effect of chronic moxonidine therapy, at increasing therapeutic doses, on resting peripheral sympathetic activity and vascular resistance and their responses to physiological reflex maneuvers. Twelve newly diagnosed patients with essential hypertension were studied sequentially at least 1 month apart, initially on no therapy, then on 200 microg, and finally on 400 microg 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 maneuvers. Peroneal microneurography was used to quantify peripheral sympathetic vasoconstrictor activity by single-unit and multiunit techniques. Moxonidine therapy progressively reduced resting mean arterial pressure (P<0.0001) without affecting heart rate. At 200 microg daily, there was a significant reduction in sympathetic nerve activity (P<0.001) and calf vascular resistance (P<0.01). At 400 microg daily, further reductions were smaller and insignificant. Responses to cold stimulus and isometric handgrip exercise showed a similar pattern, with the greatest magnitude of change at 200 microg daily. In patients with essential hypertension, chronic moxonidine therapy inhibited resting sympathetic vasoconstrictor drive and also its reflex responses. The magnitude of inhibition became less as the therapeutic dose was increased, suggesting that moxonidine may be more effective under conditions of high sympathetic activity.
Greenwood
J P
JP
Department of Cardiology, St James's University Hospital, Leeds, West Yorkshire, UK. john_greenwood@hotmail.com
Scott
E M
EM
Stoker
J B
JB
Mary
D A
DA
D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003080:Cold Temperature; D018737:Hand Strength; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D007093:Imidazoles / Q000819:agonists* / Q000627:therapeutic use*; D007537:Isometric Contraction; D007866:Leg / Q000098:blood supply; D008137:Longitudinal Studies; D008875:Middle Aged; D012018:Reflex / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000959:Antihypertensive Agents; D007093:Imidazoles; C043482:moxonidine