title: Role of nitric oxide in regulation of coronary blood flow during myocardial ischemia in dogs.
abstract: OBJECTIVE
  This study was undertaken to examine whether nitric oxide released in ischemic myocardium decreases the coronary vascular resistance and attenuates the severity of contractile and metabolic dysfunction.
  
  
  BACKGROUND
  Endothelium-derived relaxing factor, recently identified as nitric oxide, is a potent relaxant of coronary smooth muscle.
  
  
  METHODS
  The left anterior descending coronary artery was perfused through an extracorporeal bypass tube placed in the carotid artery in 56 open chest dogs. After hemodynamic stabilization, we occluded this bypass tube to decrease coronary blood flow to one third of the control flow. Thereafter, we maintained a constant coronary perfusion pressure (40.9 +/- 3.1 mm Hg).
  
  
  RESULTS
  Under ischemic conditions, the coronary arteriovenous differences in nitrate and nitrite (end products of nitric oxide) increased (from 3.5 +/- 0.4 [mean +/- SEM] to 12.9 +/- 2.1 mumol/liter, p < 0.01). NG-Monomethyl L-arginine (3 micrograms/kg body weight per min, intracoronary) decreased the coronary arteriovenous differences in nitrate and nitrite (5.0 +/- 0.9 mumol/liter, p < 0.05) and coronary blood flow (from 29.8 +/- 0.5 to 18.1 +/- 1.1 ml/100 g per min, p < 0.001). Fractional shortening (from 3.7 +/- 1.0 to -1.3 +/- 0.7%, p < 0.001) and lactate extraction ratio (from -44.0 +/- 4.1 to -59.2 +/- 4.9%, p < 0.005) of the perfused area also decreased. These values were restored by the concomitant administration of L-arginine. Blood flow to the endomyocardium was decreased relative to the epimyocardium. A reduction in coronary blood flow and worsening of myocardial contractile and metabolic functions due to the administration of NG-monomethyl L-arginine during ischemia were observed in denervated hearts. A reduction in coronary blood flow in ischemic myocardium was observed with the administration of NW-nitro-L-arginine methyl ester as well, although neither NW-nitro-L-arginine methyl ester nor NG-monomethyl L-arginine changed coronary blood flow and myocardial contractile and metabolic functions in the nonischemic myocardium. The cyclic guanosine monophosphate content of epicardial coronary artery increased due to myocardial ischemia; this increase was attenuated with NG-monomethyl L-arginine treatment.
  
  
  CONCLUSIONS
  We conclude that endogenous nitric oxide predominantly decreases the coronary vascular resistance of ischemic endomyocardium, thereby improving myocardial contractility and metabolic function.
authors.affiliation: First Department of Medicine, Osaka University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kitakaze
authors.forename: K
authors.initials: K
authors.lastname: Node
authors.forename: T
authors.initials: T
authors.lastname: Minamino
authors.forename: H
authors.initials: H
authors.lastname: Kosaka
authors.forename: Y
authors.initials: Y
authors.lastname: Shinozaki
authors.forename: H
authors.initials: H
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: T
authors.initials: T
authors.lastname: Kamada
mesh_terms: D000818:Animals; D001794:Blood Pressure; D003326:Coronary Circulation / Q000502:physiology*; D004285:Dogs; D006339:Heart Rate; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D014655:Vascular Resistance / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase