Effects of moxonidine on sympathetic nerve activity in patients with end-stage renal disease.
OBJECTIVE
End-stage renal disease (ESRD) is characterized by markedly increased sympathetic outflow that contributes to increased cardiovascular mortality in these patients. The central sympatholytic drug moxonidine (MOX) has been shown to reduce muscle sympathetic nerve activity (MSNA) in initial stages of chronic kidney disease; however, the effects in ESRD are not known. The aim of this study was to test the hypothesis that low-dose MOX causes sustained decreases in sympathetic outflow in ESRD patients.


METHODS
Twenty-three ESRD patients (mean age 46.4 +/- 16 years, 14 men, seven women, no diabetic patients) were randomized to a daily treatment of 0.3 mg MOX or placebo (PLA) in addition to pre-existing antihypertensive therapy. At baseline and after 1 and 6 months of treatment, heart rate (HR, ECG), blood pressure (mean arterial pressure, automatic sphygmanometer), calf blood flow (CBF, venous occlusion plethysmography), muscle sympathetic nerve activity (MSNA) (microneurography at the peroneal nerve) were measured. Data are mean +/- SEM.


RESULTS
MOX acutely decreased MSNA within 2 h after oral intake (from 45 +/- 3.7 to 35 +/- 3.9 bursts/min, P < 0.05). This decrease was sustained over 6 months (MSNA 45 +/- 3.7, 35 +/- 4.6, 33 +/- 4.5 bursts/min at 0, 1 and 6 months, P < 0.05). PLA had no effect. Neither MOX nor PLA resulted in any significant acute or long-term changes in HR, MAP or CBF.


CONCLUSIONS
In ESRD patients, low-dose MOX produced sustained and substantial reductions in sympathetic outflow without hemodynamically compromising them. We suggest that the inhibition of central sympathetic outflow may improve cardiovascular prognosis in ESRD.
Hausberg
Martin
M
Department of Internal Medicine D, University of Muenster, Muenster, Germany.
Tokmak
Faruk
F
Pavenstädt
Hermann
H
Krämer
Bernhard K
BK
Rump
Lars Christian
LC
D000328:Adult; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology*; D013565:Sympatholytics / Q000627:therapeutic use*
D007093:Imidazoles; D013565:Sympatholytics; C043482:moxonidine