title: Influence of nitric oxide synthase and adrenergic inhibition on adenosine-induced myocardial hyperemia.
abstract: BACKGROUND
  Myocardial perfusion during adenosine-induced hyperemia is used both in clinical diagnosis of coronary heart disease and for scientific investigations of the myocardial microcirculation. The objective of this study was to clarify whether adenosine-induced hyperemia is dependent on endothelial NO production or is influenced by adrenergic mechanisms.
  
  
  RESULTS
  In 12 healthy men, myocardial perfusion was measured with PET in 2 protocols performed in random order, each including 3 perfusion measurements. First, perfusion was measured at rest. Second, either saline or the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 4 mg/kg) was infused, and perfusion during adenosine-induced hyperemia was determined. Last, in both protocols, the alpha-receptor blocker phentolamine was infused, and perfusion during adenosine-induced hyperemia was determined again. Resting perfusion was similar in the 2 protocols (0.69+/-0.14 and 0.66+/-0.18 mL. min(-1). g(-1)). L-NAME increased mean arterial blood pressure by 12+/-7 mm Hg (P<0.01) and reduced heart rate by 16+/-7 bpm (P<0.01). Adenosine-induced hyperemia (1.90+/-0.33 mL. min(-1). g(-1)) was attenuated by L-NAME (1.50+/-0.55 mL. min(-1). g(-1), P<0.01). The addition of phentolamine had no effect on the adenosine-induced hyperemia (2.10+/-0.34 mL. min(-1). g(-1), P=NS). In the presence of L-NAME, however, when the adenosine response was attenuated, phentolamine was able to increase hyperemic perfusion (2.05+/-0.44 mL. min(-1). g(-1), P<0.05).
  
  
  CONCLUSIONS
  Inhibition of endogenous NO synthesis attenuates myocardial perfusion during adenosine-induced hyperemia, indicating that coronary vasodilation by adenosine is partly endothelium dependent. alpha-Adrenergic blockade has no effect on adenosine-induced hyperemia unless NO synthesis is inhibited.
authors.affiliation: Center for Clinical Pharmacology, Department of Cardiology, PET Center, Aarhus University Hospital, Denmark. nhb@farm.au.dk
authors.forename: N H
authors.initials: NH
authors.lastname: Buus
authors.forename: M
authors.initials: M
authors.lastname: Bøttcher
authors.forename: F
authors.initials: F
authors.lastname: Hermansen
authors.forename: M
authors.initials: M
authors.lastname: Sander
authors.forename: T T
authors.initials: TT
authors.lastname: Nielsen
authors.forename: M J
authors.initials: MJ
authors.lastname: Mulvany
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006940:Hyperemia / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010646:Phentolamine / Q000494:pharmacology; D014055:Tomography, Emission-Computed; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester; D010646:Phentolamine