title: 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.
  
  
  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.
authors.affiliation: Johns Hopkins Medical Institutions, Johns Hopkins School of Medicine, Baltimore, Md, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Hare
authors.forename: M M
authors.initials: MM
authors.lastname: Givertz
authors.forename: M A
authors.initials: MA
authors.lastname: Creager
authors.forename: W S
authors.initials: WS
authors.lastname: Colucci
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000503:physiopathology; D004280:Dobutamine / Q000494:pharmacology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D018487:Ventricular Dysfunction, Left / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D004280:Dobutamine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine