Reduction of Sympathetic Hyperactivity by Enalapril in Patients with Chronic Renal Failure
Gerry Ligtenberg, M.D., Ph.D., Peter J. Blankestijn, M.D., Ph.D., P. Liam Oey, M.D., Ph.D., Inge H.H. Klein, M.D., Lioe-Ting Dijkhorst-Oei, M.D., Frans Boomsma, Ph.D., George H. Wieneke, Ph.D., Alexander C. van Huffelen, M.D., Ph.D., and Hein A. Koomans, M.D., Ph.D.
Background Inhibition of angiotensin-converting enzyme (ACE)reduces the risk of cardiovascular problems in patients withchronic renal failure. This effect may be due in part to a decreasein sympathetic nervous activity, but no direct evidence of suchan action is available.
Methods We studied muscle sympathetic-nerve activity in 14 patientswith hypertension, chronic renal failure, and increased plasmarenin activity before, during, and after administration of theACE inhibitor enalapril. Ten other patients with similar clinicalcharacteristics were studied before and during treatment withthe calcium-channel blocker amlodipine. Normal subjects matchedfor age and weight were included in both studies.
Results At base line, mean (±SD) muscle sympathetic-nerveactivity was higher in the group of patients who received enalaprilthan in the control subjects (35±17 vs. 19±9 burstsper minute, P=0.004). The baroreflex curve, which reflects changesin muscle sympathetic-nerve activity caused by manipulationsof blood pressure with sodium nitroprusside and phenylephrine,was shifted to the right in the patients, but baroreflex sensitivitywas similar to that in the control subjects (2.1±1.9and 2.7±1.3 bursts per minute per mm Hg, respectively;P=0.36). A single dose of the sympatholytic drug clonidine causeda greater fall in blood pressure in the patients than in thecontrol subjects. Treatment with enalapril normalized bloodpressure and muscle sympathetic-nerve activity (at 23±10bursts per minute) in the patients and shifted the baroreflexcurve to the left, reflecting normal blood-pressure levels,without significantly changing sensitivity (2.3±1.8bursts per minute per mm Hg, P=0.96). In the patients who receivedamlodipine, treatment also lowered blood pressure but increasedmuscle sympathetic-nerve activity, from 41±19 to 56±14bursts per minute (P=0.02).
Conclusions Increased sympathetic activity contributes to hypertensionin patients with chronic renal disease. ACE inhibition controlshypertension and decreases sympathetic hyperactivity.
Source Information
From the Departments of Nephrology and Hypertension (G.L., P.J.B., I.H.H.K., L.-T.D.-O., H.A.K.) and Clinical Neurophysiology (P.L.O., G.H.W., A.C.H.), University Hospital Utrecht, Utrecht; and the Department of Internal Medicine, University Hospital Rotterdam, Rotterdam (F.B.) both in the Netherlands.
Address reprint requests to Dr. Ligtenberg at the Department of Nephrology and Hypertension, University Hospital Utrecht, Rm. F03.226, P.O. Box 85.500, 3508 GA Utrecht, the Netherlands, or at gligtenb{at}digd.azu.nl.
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