title: Blockade of nitric oxide synthesis reduces myocardial oxygen consumption in vivo.
abstract: BACKGROUND
  Although cardiac myocytes and coronary vascular endothelium are known to express a constitutive form of NO synthase, the in vivo effects of tonic endogenous production of NO on myocardial O2 consumption and contractile performance remain unclear.
  
  
  RESULTS
  The effects of blockade of NO synthase were determined in intact dogs. Myocardial O2 consumption decreased systematically over a wide range of hemodynamic demand after the systemic administration of N omega-nitro-L-arginine methyl ester (L-NAME) or N omega-nitro-L-arginine. Decreases after doses of 1 and 10 mg/kg L-NAME averaged 23 +/- 3.8% and 34 +/- 7.2% at a heart rate of 90 bpm in open-chest animals. Similar reductions occurred after the administration of L-NAME and N omega-nitro-L-arginine in chronically instrumented animals and were unaffected by beta-adrenergic blockade. Intracoronary infusion of L-NAME in chronically instrumented animals reduced both myocardial O2 consumption and regional segment shortening, even at a dose that did not increase systemic arterial pressure.
  
  
  CONCLUSIONS
  The blockade of NO synthesis reduces myocardial O2 consumption in vivo. The decrease in O2 consumption is accompanied by a decrease in segment shortening. It involves a direct myocardial action of NO, is unaffected by beta-blockade, and is consistent with in vitro studies indicating that low levels of NO augment contractile performance by inhibition of a cGMP-dependent phosphodiesterase.
authors.affiliation: Feinberg Cardiovascular Research Institute, Department of Medicine, Northwestern University Medical School, Chicago, III 60611-3008, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Sherman
authors.forename: C A
authors.initials: CA
authors.lastname: Davis
authors.forename: F J
authors.initials: FJ
authors.lastname: Klocke
authors.forename: K R
authors.initials: KR
authors.lastname: Harris
authors.forename: G
authors.initials: G
authors.lastname: Srinivasan
authors.forename: A S
authors.initials: AS
authors.lastname: Yaacoub
authors.forename: D A
authors.initials: DA
authors.lastname: Quinn
authors.forename: K A
authors.initials: KA
authors.lastname: Ahlin
authors.forename: J J
authors.initials: JJ
authors.lastname: Jang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D002245:Carbon Dioxide; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester