Increased sensitivity to nitric oxide synthase inhibition in patients with heart failure -: Potentiation of β-adrenergic inotropic responsiveness

Background-We previously showed that cardiac nitric oxide (NO) inhibits the positive inotropic response to beta-adrenergic stimulation in humans with left ventricular (LV) dysfunction. Whether this effect is specific to heart failure per se or is a generalized feature of normal human myocardium is unknown. We therefore tested the hypothesis that inhibition of cardiac NO potentiates the positive inotropic response to beta-adrenergic stimulation in patients with symptomatic LV failure but not in subjects with normal LV function. Methods and Results-We studied 11 patients with LV failure due to idiopathic dilated cardiomyopathy and 7 control subjects with normal LV function. The beta-adrenergic agonist dobutamine was infused via a peripheral vein before and during concurrent intracoronary artery infusion of acetylcholine, which activates the agonist-coupled isoforms of NO synthase, and N-G-monomethyl-L-arginine, which inhibits all isoforms of NO synthase. Changes in contractility were assessed by measuring the peak rate of rise of LV pressure (+dP/dt). Dobutamine increased +dP/dt by 40+/-6% and 73+/-14% in patients with heart failure and control subjects, respectively. Acetylcholine inhibited the +dP/dt response to dobutamine to a similar degree in patients with heart failure and control subjects (-39+/-8% and -31+/-4%, respectively; P=NS). infusion of N-G-monomethyl-L-arginine potentiated the +dP/dt response to dobutamine by 51+/-15% (P=.01 versus dobutamine) in patients with heart failure but had no effect in control subjects (-6+/-4%; P=NS versus dobutamine; P=.0002 versus heart failure patients). Conclusions-Inhibition of cardiac NO augments the positive inotropic response to beta-adrenergic receptor stimulation in patients with heart failure due to idiopathic dilated cardiomyopathy but not in control subjects with normal LV function.