Lisinopril lowers cardiac adrenergic drive and increases beta-receptor density in the failing human heart.
BACKGROUND In subjects with heart failure, angiotensin converting enzyme inhibitors exhibit mild systemic antiadrenergic effects, as deduced from treatment-related lowering of systemic venous norepinephrine levels. The effects of angiotensin converting enzyme inhibitors on cardiac 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 systemic adrenergic drive, myocardial and lymphocyte beta-adrenergic receptors, and hemodynamic changes at baseline and after 12 weeks of therapy. Relative to placebo, lisinopril therapy was associated with only minimal, 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 change in lymphocyte beta-receptor density. When subjects were rank ordered into groups with the highest and lowest coronary sinus norepinephrine levels, those with the highest norepinephrine levels exhibited significant decreases in central venous norepinephrine, coronary sinus norepinephrine, and an increase in myocardial beta-receptor density relative to changes in placebo or relative to baseline values. Subjects with lower cardiac adrenergic drive exhibited no significant changes in coronary sinus or systemic norepinephrine levels or in myocardial beta-receptor density.
CONCLUSIONS The angiotensin converting enzyme inhibitor lisinopril lowered cardiac adrenergic drive and increased beta-receptor density in subjects with increased cardiac adrenergic drive but had no effects on these parameters in subjects with normal cardiac adrenergic drive. These data suggest that cardiac antiadrenergic properties contribute to the efficacy of angiotensin converting enzyme inhibitor in subjects with heart failure.
- Copyright © 1993 by American Heart Association