Dissociation between ACE activity and autonomic response to ACE inhibitionin patients with heart failure

Background Administration of angiotensin-converting enzyme (ACE) inhibitors to patients with congestive heart failure has been shown to increase paras ympathetic tone as indicated by increases in high-frequency heart rate vari ability. The mechanism for this effect including its relation to changes in baroreflex activity, blood pressure variability, and suppression of ACE ac tivity, remains undefined. This study was designed to test the relation of these variables, which may govern changes in autonomic activity, to the pre viously described increase in parasympathetic tone. Methods seven patients with heart failure received a 3-hour infusion of the ACE inhibitor enalaprilat. Hemodynamic variables and parameters of heart r ate and blood pressure variability, baroreflex gain derived from the intera ction of heart rate and blood pressure variability, and serum ACE activity were measured during and after the infusion. Measures of heart rate and blo od pressure variability were also compared against a historic control group . Results serum ACE activity was significantly suppressed throughout and afte r enalaprilat infusion. Hemodynamic measures did not change other than a sm all decline in right atrial and pulmonary capillary wedge pressures. Parasy mpathetic tone showed an initial significant increase with a peak at 2 hour s but then declined below baseline 8 hours after initiation of enalaprilat infusion. Sympathetically influenced low-frequency heart rate variability w as significantly increased above baseline in the enalaprilat treatment grou p 8 hours after initiation of the infusion. Baroreflex gain showed a signif icant trend to an increase with the maximum value coinciding with the peak in parasympathetic tone. There was no change in blood pressure variability in the enalaprilat group and no change in baroreflex gain, heart rate varia bility, or blood pressure variability in the control group. Conclusions Parasympathetic tone and baroreflex gain increased with parente ral administration of an ACE inhibitor but subsequently decreased below bas eline values despite continued suppression of serum ACE activity. The disso ciation between ACE suppression and autonomic response to ACE inhibition in dicates that enzyme systems not reflected by plasma ACE activity or indepen dent from the classic pathways of angiotensin formation contribute to the r egulation of the autonomic response to ACE inhibition in patients with hear t failure. The absence of significant change in hemodynamic variables or in blood pressure variability indicates that these autonomic changes are not an indirect reflex response to ACE inhibitor-induced vasodilation or hemody namic baroreceptor stimulation.