title: Effects of nitric oxide synthase inhibition on myocardial capillary permeability and reactive hyperaemic response.
abstract: OBJECTIVE
  The aim was to examine the role of nitric oxide (NO) in the myocardial microcirculation.
  
  
  METHODS
  Open chest anaesthetised dogs received intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA; 0.5 mg.kg-1 over 30 min). Myocardial microvascular extraction fraction of a small hydrophilic solute (technetium 99m labelled diethylenetriaminepenta-acetate [99mTc-DTPA]), and the regional myocardial plasma flow rate, were determined by the single injection, residue detection method, and the capillary permeability-surface area product was calculated. The tone in intramyocardial resistance vessels was assessed by the local 133Xe washout method during baseline conditions, in response to intracoronary acetylcholine, and during peak reactive hyperaemia after 10 s or 30 s of myocardial ischaemia, respectively.
  
  
  RESULTS
  In eight open chest dogs, L-NMMA attenuated the increase in myocardial plasma flow rate in response to intracoronary acetylcholine by 32(SEM 7)%, but failed to alter baseline myocardial plasma flow rate significantly, as determined by the local 133Xe washout method. L-NMMA did not influence myocardial microvascular permeability to 99mTc-DTPA. However, intracoronary L-NMMA decreased the peak reactive hyperaemic myocardial plasma flow rate after 10 s, but not 30 s, of coronary occlusion.
  
  
  CONCLUSIONS
  In open chest dogs, microvascular NO synthesis is not a major determinant of baseline myocardial plasma flow rate, and does not appear to influence myocardial microvascular permeability significantly. In this model, NO intervenes in the regulation of the peak reactive hyperaemic plasma flow rate following brief, but not more prolonged, periods of coronary occlusion.
authors.affiliation: Department of Medicine B (Division of Cardiology), Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: P R
authors.initials: PR
authors.lastname: Hansen
authors.forename: S
authors.initials: S
authors.lastname: Haunsø
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006940:Hyperemia / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000503:physiopathology; D009252:NADPH Dehydrogenase / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics*; D019323:omega-N-Methylarginine
chemical_list: D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase; D000109:Acetylcholine; D016284:Technetium Tc 99m Pentetate