ACUTE AND LONG-TERM EFFECTS OF THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR, ENALAPRIL, ON ADRENERGIC ACTIVITY AND SENSITIVITY DURING EXERCISE IN PATIENTS WITH LEFT-VENTRICULAR SYSTOLIC DYSFUNCTION

Patients with heart failure and left ventricular systolic dysfunction exhibit increased adrenergic activity but blunted adrenergic responsiv eness. We studied patients enrolled in the Studies of left Ventricular Dysfunction, examining exercise responses of heart rate (HR) and plas ma norepinephrine (PNE). Eighty-seven patients were studied before ran domization; 65 of these were examined 1 year after randomization to pl acebo or enalapril. Compared with prevention trial (asymptomatic) pati ents, patients in the treatment trial (symptomatic) had higher resting HR and PNE levels and less increase in HR with a greater increase in PNE with exercise. Acute administration of enalapril increased the res ting HR in patients in the prevention trial only but had no significan t effect on PNE. After 7 year of therapy, patients in the prevention t rial exhibited no change. Within the treatment trial, the placebo grou p displayed both a higher peak PNE and increase in PNE with exercise t han did the enalapril group, whose HR response was maintained in spite of a reduction of exercise PNE. We conclude that (1) compared with as ymptomatic patients, symptomatic patients with reduced left ventricula r election fraction manifest greater resting and exercise adrenergic a ctivity, with blunted HR response; and (2) in symptomatic patients, 1 year of enalapril treatment effected an augmented HR response to adren ergic stimulation, supporting an interaction between the renin/angiote nsin and adrenergic nervous systems. Normalization of adrenergic tone and response likely contributes to the benefits of long-term angiotens in-converting enzyme inhibitor therapy.