Enalapril and
losartan reduce but not normalize sympathetic hyperactivity in patients with hypertensive
chronic renal failure (CRF). This study assessed the effect of chronic
eprosartan on BP and sympathetic activity, and assessed the effect of
moxonidine during chronic
eprosartan treatment. In 11 stable patients with CRF (
creatinine clearance 47 +/- 10 ml/min), muscle sympathetic nerve activity (MSNA; peroneal nerve), BP, and baroreceptor sensitivity were measured in the absence of
antihypertensive drugs (except
diuretics) during chronic
eprosartan therapy (600 mg for 6 wk) and in 9 patients after
moxonidine (0.2 mg for 6 wk) was added. Normovolemia was controlled by
diuretics and confirmed by extracellular fluid volume measurements. BP, heart rate, and MSNA were higher in patients than in 22 controls. During
eprosartan therapy, mean arterial pressure (111 +/- 9 to 98 +/- 7 mmHg, P < 0.001), heart rate (71 +/- 10 to 65 +/- 8 bpm, P < 0.001), and MSNA (35 +/- 10 to 27 +/- 8 bursts/min, P < 0.001) decreased. After the addition of
moxonidine (n = 9), a further reduction of mean arterial pressure to 89 +/- 7 mmHg (P < 0.05) and of MSNA to 20 +/- 10 bursts/min (P < 0.05) occurred. Sympathetic activity in patients with CRF can be normalized, and
angiotensin II-independent sympathetic hyperactivity contributes to the pathogenesis of
renal hypertension. Sympathetic hyperactivity is associated with poor cardiovascular outcomes, implying that reduction might be beneficial to the patients. The addition of
moxonidine to
angiotensin II antagonist treatment might be appropriate.