Increased sensitivity to nitric oxide synthase inhibition in patients with heart failure

Potentiation of β-adrenergic inotropic responsiveness

Joshua Hare, Michael M. Givertz, Mark A. Creager, Wilson S. Colucci

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Background - We previously showed that cardiac nitric oxide (NO) inhibits the positive inotropic response to β-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 β-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 β-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 β- adrenergic receptor stimulation in patients with heart failure due to idiopathic dilated cardiomyopathy but not in control subjects with normal LV function.

Original languageEnglish
Pages (from-to)161-166
Number of pages6
JournalCirculation
Volume97
Issue number2
StatePublished - Mar 31 1998
Externally publishedYes

Fingerprint

Dobutamine
Nitric Oxide Synthase
Adrenergic Agents
Heart Failure
Left Ventricular Function
Nitric Oxide
Dilated Cardiomyopathy
Acetylcholine
Arginine
Protein Isoforms
Adrenergic Agonists
Left Ventricular Dysfunction
Ventricular Pressure
Adrenergic Receptors
Veins
Myocardium
Arteries

Keywords

  • Cardiomyopathy
  • Contractility
  • Heart failure
  • Nitric oxide
  • Receptors, adrenergic, beta

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Increased sensitivity to nitric oxide synthase inhibition in patients with heart failure : Potentiation of β-adrenergic inotropic responsiveness. / Hare, Joshua; Givertz, Michael M.; Creager, Mark A.; Colucci, Wilson S.

In: Circulation, Vol. 97, No. 2, 31.03.1998, p. 161-166.

Research output: Contribution to journalArticle

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abstract = "Background - We previously showed that cardiac nitric oxide (NO) inhibits the positive inotropic response to β-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 β-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 β-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 β- adrenergic receptor stimulation in patients with heart failure due to idiopathic dilated cardiomyopathy but not in control subjects with normal LV function.",
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AU - Givertz, Michael M.

AU - Creager, Mark A.

AU - Colucci, Wilson S.

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N2 - Background - We previously showed that cardiac nitric oxide (NO) inhibits the positive inotropic response to β-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 β-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 β-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 β- adrenergic receptor stimulation in patients with heart failure due to idiopathic dilated cardiomyopathy but not in control subjects with normal LV function.

AB - Background - We previously showed that cardiac nitric oxide (NO) inhibits the positive inotropic response to β-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 β-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 β-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 β- adrenergic receptor stimulation in patients with heart failure due to idiopathic dilated cardiomyopathy but not in control subjects with normal LV function.

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