title: Augmented alpha-adrenergic constriction of atherosclerotic human coronary arteries.
abstract: BACKGROUND
  Although adrenergic activation plays a major role in the initiation of experimental myocardial ischemia, the significance of alpha-adrenergic coronary constriction in humans has been questioned. The present study assessed the impact of selective alpha-adrenergic receptor activation in patients with normal or atherosclerotic coronary arteries.
  
  
  RESULTS
  In 39 patients, coronary blood flow (CBF, mL/min) was determined from combined angiography and Doppler measurements. In 8 patients with normal coronary arteries (group 1) and 9 with single coronary artery stenosis (group 2), doses of 1, 2.5, 5, and 10 mg IC of the alpha1-agonist methoxamine (M) were injected. Identical doses of the alpha2-agonist BHT933 (B) were injected in 8 patients with normal coronary arteries (group 3) and 8 with single stenosis (group 4). In 6 additional patients with single stenosis (group 5), aortocoronary sinus lactate differences were measured in response to M and B. CBF remained unchanged in group 1. In contrast, CBF was decreased dose-dependently in group 2, with a maximum at 10 mg M (39.0+/-9.4 versus 15.2+/-7.0). In groups 3 and 4, CBF was also decreased dose-dependently, with a maximum at 10 mg B (63.3+/-24.8 versus 49. 1+/-27.9 and 41.5+/-19.0 versus 12.7+/-8.0, respectively). In group 5, there was more net lactate production with B than with M (-0. 34+/-0.11 versus -0.04+/-0.09 mmol/L).
  
  
  CONCLUSIONS
  In normal coronary arteries, alpha1-adrenergic activation does not reduce CBF, whereas alpha2-adrenergic activation reduces CBF by microvascular constriction. Both alpha1- and alpha2-adrenergic epicardial and microvascular constriction are augmented by atherosclerosis and can induce myocardial ischemia.
authors.affiliation: Departments of Cardiology and Pathophysiology (G.H.), Center of Internal Medicine, University of Essen, Germany. dbaum3@t-online.de
authors.forename: D
authors.initials: D
authors.lastname: Baumgart
authors.forename: M
authors.initials: M
authors.lastname: Haude
authors.forename: G
authors.initials: G
authors.lastname: Görge
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Ge
authors.forename: C
authors.initials: C
authors.lastname: Grosse-Eggebrecht
authors.forename: R
authors.initials: R
authors.lastname: Erbel
authors.forename: G
authors.initials: G
authors.lastname: Heusch
mesh_terms: D000316:Adrenergic alpha-Agonists; D001783:Blood Flow Velocity / Q000187:drug effects; D006328:Cardiac Catheterization; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003331:Coronary Vessels / Q000502:physiology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008729:Methoxamine; D008875:Middle Aged; D011859:Radiography; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D014463:Ultrasonography; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D008729:Methoxamine