title: Inhibition of endogenous nitric oxide synthase augments contractile response to adenylyl cyclase stimulation without altering mechanical efficiency in patients with idiopathic dilated cardiomyopathy.
abstract: BACKGROUND
  Increased nitric oxide (NO) in the failing heart attenuates the myocardial contractile response to beta-adrenergic receptor stimulation. However, the physiological effects of NO on the beta-adrenergic post-receptor signaling system are unknown. The objective of the present study was to examine the effects of cardiac NO synthase (NOS) inhibition on left ventricular (LV) hemodynamics and mechanoenergetics in response to adenylyl cyclase stimulation in human heart failure.
  
  
  RESULTS
  The study group comprised 13 patients with heart failure because of idiopathic cardiomyopathy (IDC). Emax was examined as an index of LV contractility, LV external work (EW), pressure-volume area (PVA), myocardial oxygen consumption (MVO2), and mechanical efficiency (EW/MVO2) with the use of conductance and coronary sinus thermodilution catheters before and during colforsin daropate infusion, and during concurrent infusion of colforsin daropate with the NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA; 200 micromol). Colforsin daropate increased Emax by 53% and EW by 18%, and reduced PVA by 14%, without altering MVO2 or mechanical efficiency. The combination of colforsin daropate with L-NMMA further increased Emax by 26% and reduced PVA by 9%, without altering MVO2 or mechanical efficiency.
  
  
  CONCLUSIONS
  These findings suggest endogenous NO may modulate beta-adrenergic post-receptor pathways and preserve myocardial efficiency in patients with IDC.
authors.affiliation: Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University, Graduate School of Medicine, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ohta
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shinke
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hata
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takaoka
authors.forename: Junya
authors.initials: J
authors.lastname: Shite
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kijima
authors.forename: Takeomi
authors.initials: T
authors.lastname: Murata
authors.forename: Ryohei
authors.initials: R
authors.lastname: Yoshikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Masai
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: D000262:Adenylyl Cyclases / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists; D000368:Aged; D001696:Biomechanical Phenomena; D002311:Cardiomyopathy, Dilated / Q000150:complications*; D005576:Colforsin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006333:Heart Failure / Q000209:etiology; D006334:Heart Function Tests; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors*; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; C122001:colforsin daropate; D005576:Colforsin; D019323:omega-N-Methylarginine; D052250:Nitric Oxide Synthase Type III; D000262:Adenylyl Cyclases