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(Circulation. 1997;96:1173-1179.)
© 1997 American Heart Association, Inc.
Articles |
Effects of Chronic ACE Inhibition on Sympathetic Nerve Traffic and Baroreflex Control of Circulation in Heart Failure
From the Cattedra di Medicina Interna, Università di Milano, Ospedale S. Gerardo, Monza (G.G., M.P., S.C., G.M.); Centro di Fisiologia Clinica e Ipertensione, Università di Milano e Ospedale Maggiore, Milano (G.G., B.M.C., A.L., A.M., G.M.); and Centro Auxologico Italiano, Milano (B.M.C., G.S., G.M.), Italy.
Correspondence to Professor Giuseppe Mancia, I Divisione di Medicina, Cattedra di Medicina Interna, Ospedale S. Gerardo dei Tintori, Via Donizetti 106, 20052 Monza, Italy.
Background In congestive heart failure ACE inhibitors chronically reduce plasma norepinephrine. No information exists, however, on whether and to what extent this reduction reflects a true chronic inhibition of sympathetic outflow and which mechanisms may be responsible.
Methods and Results In 24 patients aged 60.3±2.0 years (mean±SEM) affected by congestive heart failure (New York Heart Association class II) and treated with diuretics and digitalis, we measured mean arterial pressure (Finapres), plasma renin activity and angiotensin II levels (radioimmunoassay), plasma norepinephrine (high-performance liquid chromatography), and muscle sympathetic nerve activity (microneurography at a peroneal nerve) at rest and during baroreceptor stimulation and deactivation caused by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. In 12 patients measurements were repeated after a 2-month addition of the ACE inhibitor benazepril (10 mg/d PO), while in the remaining 12 patients they were performed again after 2 months without any treatment modifications. Benazepril did not alter mean arterial pressure, markedly increased plasma renin activity, reduced plasma angiotensin II, and caused a nonsignificant reduction in plasma norepinephrine. In contrast, muscle sympathetic nerve traffic was significantly reduced (-30.5±5.3%, P<.01). This reduction was accompanied by no change in the sympathoexcitatory responses to baroreceptor deactivation but by a marked enhancement of the sympathoinhibitory responses to baroreceptor stimulation (103.5±3.4%).
Conclusions These results provide the first direct evidence that in congestive heart failure chronic ACE inhibitor treatment is accompanied by a marked reduction in central sympathetic outflow. This reduction may depend on a persistent restoration of baroreflex restraint on the sympathetic neural drive.
Key Words: heart failure • reflex • nervous system • baroreceptors • renin • angiotensin
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