LISINOPRIL LOWERS CARDIAC ADRENERGIC DRIVE AND INCREASES BETA-RECEPTOR DENSITY IN THE FAILING HUMAN HEART

Background. In subjects with heart failure, angiotensin converting enz yme inhibitors exhibit mild systemic antiadrenergic effects, as deduce d from treatment-related lowering of systemic venous norepinephrine le vels. The effects of angiotensin converting enzyme inhibitors on cardi ac adrenergic drive in subjects with heart failure has not previously been investigated. Methods and Results.In a placebo-controlled, double -blind crossover study of 14 patients, we measured cardiac and systemi c adrenergic drive, myocardial and lymphocyte beta-adrenergic receptor s, and hemodynamic changes at baseline and after 12 weeks of therapy. Relative to placebo, lisinopril therapy was associated with only minim al, statistically insignificant changes in hemodynamics, a significant increase in myocardial beta-receptor density, no significant (P<.05) changes in cardiac or systemic adrenergic drive, and no detectable cha nge in lymphocyte beta-receptor density. When subjects were rank order ed into groups with the highest and lowest coronary sinus norepinephri ne levels, those with the highest norepinephrine levels exhibited sign ificant decreases in central venous norepinephrine, coronary sinus nor epinephrine, and an increase in myocardial beta-receptor density relat ive to changes in placebo or relative to baseline values. Subjects wit h lower cardiac adrenergic drive exhibited no significant changes in c oronary sinus or systemic norepinephrine levels or in myocardial beta- receptor density. Conclusions. The angiotensin converting enzyme inhib itor lisinopril lowered cardiac adrenergic drive and increased beta-re ceptor density in subjects with increased cardiac adrenergic drive but had no effects on these parameters in subjects with normal cardiac ad renergic drive. These data suggest that cardiac antiadrenergic propert ies contribute to the efficacy of angiotensin converting enzyme inhibi tor in subjects with heart failure.