Author + information
- Received March 29, 1995
- Revision received September 21, 1995
- Accepted September 26, 1995
- Published online February 1, 1996.
- Mark E. Dibner-Dunlap, MD,FACC*,1,
- Michael L. Smith, PhD,
- Toru Kinugawa, MD2 and
- Marc D. Thames, MD,FACC
- ↵*Address for correspondence: Dr. Mark E. Dibner-Dunlap, Medical Research Service 151 W, Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, Ohio 44106.
Objectives. This study sought to determine the effects of enalaprilat on reflex control of sympathetic nerve activity.
Background. Angiotensin-converting enzyme inhibitors decrease mortality in patients with congestive heart failure. Their efficacy appears to be related importantly to antiadrenergic effects, the mechanism for which has not been determined. Because baroreflexes tonically inhibit sympathetic outflow, and baroreflexes are blunted in heart failure, we hypothesized that these agents reduce sympathetic activity by augmenting baroreflexes.
Methods. We assessed baroreflex control sympathetic nerve activity and heart rate in patients with congestive heart failure and in control subjects before and after enalaprilat (0.02 mg/kg body weight intravenously). Arterial baroreflexes were perturbed by bolus administration of sodium nitroprusside and phenylephrine. Cardiopulmonary baroreflexes were perturbed by lower body negative pressure and head-down tilt. Muscle sympathetic nerve activity was recorded by microneurography.
Results. Enalaprilat decreased systolic blood pressure in patients with heart failure and control subjects. Sympathetic nerve activity increased in control subjects but decreased in patients with heart failure after enalaprilat despite reductions in central venous pressure in this group. Baroreflex control of sympathetic nerve activity was unchanged by enalaprilat in control subjects. In patients with heart failure, both arterial and cardiopulmonary baroreflex control of sympathetic nerve activity was enhanced by enalaprilat. Baroreflex control of heart rate was unchanged by enalaprilat in either group.
Conclusions. Enalaprilat augments both arterial and cardiopulmonary baroreflex control of sympathetic activity in heart failure. These augmented inhibitory influences are associated with a reduction in sympathetic outflow and may contribute to the beneficial effects of angiotensin-converting enzyme inhibitors in heart failure.
↵1 Dr. Dibner-Dunlap is the recipient of a Clinical Investigator Award from the Department of Veterans Affairs.
↵2 Dr. Kinugawa is the recipient of a Research Fellowship Award from the American Heart Association, Northeast Ohio Affiliate, Inc.
This work was supported by funds from the Medical Research Service of the Department of Veterans Affairs, Washington, D.C.; by Grant HL 30506 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; and by a Medical School Grant from Merck Human Health Division, West Point, Pennsylvania.
- Received March 29, 1995.
- Revision received September 21, 1995.
- Accepted September 26, 1995.