Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure

Background Inhibition of angiotensin-converting enzyme (ACE) reduces the ri sk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, bu t no direct evidence of such an action is available. Methods We studied muscle sympathetic-nerve activity in 14 patients with hy pertension, chronic renal failure, and increased plasma renin activity befo re, during, and after administration of the ACE inhibitor enalapril. Ten ot her patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjec ts matched for age and weight were included in both studies. Results At base line, mean (+/-SD) muscle sympathetic-nerve activity was hi gher in the group of patients who received enalapril than in the control su bjects (35+/-17 vs. 19+/-9 bursts per minute, P = 0.004). The baroreflex cu rve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine , was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts p er minute per mm Hg, respectively; P = 0.36). A single dose of the sympatho lytic drug clonidine caused a greater fall in blood pressure in the patient s than in the control subjects. Treatment with enalapril normalized blood p ressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute ) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (- 2.3+/-1.8 bursts per minute per mm Hg, P = 0.96). In the patients who recei ved amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P = 0.02). Conclusions Increased sympathetic activity contributes to hypertension in p atients with chronic renal disease. ACE inhibition controls hypertension an d decreases sympathetic hyperactivity. (N Engl J Med 1999;340:1321-8.) (C)1 999, Massachusetts Medical Society.