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

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(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.

020406080'00'02'04'06'08'10'12'14'16
Citations per Year

459 Citations

Semantic Scholar estimates that this publication has 459 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Hare1998IncreasedST, title={Increased sensitivity to nitric oxide synthase inhibition in patients with heart failure: potentiation of beta-adrenergic inotropic responsiveness.}, author={Joshua M Hare and Michael M . Givertz and Mark A . Creager and Wilson Steven Colucci}, journal={Circulation}, year={1998}, volume={97 2}, pages={161-6} }