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

Hare, J.M.; Givertz, M.M.; Creager, M.A.; Colucci, W.S.

Circulation 97(2): 161-166

1998


ISSN/ISBN: 0009-7322
PMID: 9445168
DOI: 10.1161/01.cir.97.2.161
Accession: 008851516

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Abstract
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-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 4O+-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 NG-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.