title: Alterations of alpha-adrenergic modulations of coronary microvascular tone in dogs with heart failure.
abstract: BACKGROUND
  It remains unclear whether coronary microvascular response to alpha-adrenergic activation alters in chronic heart failure (CHF).
  
  
  RESULTS
  We investigated the alpha-adrenergic receptor-mediated effects on coronary pressure-flow relationship (CPFR) in a tachycardia-induced canine heart failure model. The dogs studied were male (29 of 31) and the drugs were given intracoronary. The slope of CPFR during long diastole was evaluated as an index of coronary vascular resistance, during alpha1- or alpha2-adrenergic stimulation or inhibition under anesthesia in the baseline and failing state after 3 weeks of rapid ventricular pacing. Resting coronary blood flow and CPFR did not change in the failing state from the baseline state. Neither alpha1 nor alpha2 stimulation changed the slope of CPFR in the baseline state. However, in the failing state, alpha1 stimulation decreased the slope of CPFR by 23 +/- 5% (P < .05), whereas alpha2 stimulation increased it by 73 +/- 10% (P < .05), which was nearly abolished by pretreatment with NG-nitro-L-arginine methyl ester.
  
  
  CONCLUSIONS
  Alpha2-mediated vasodilatory action, presumably via endothelium-derived nitric oxide release, would be enhanced in the coronary microvascular bed, which may antagonize enhanced alpha1-induced vasoconstriction in CHF.
authors.affiliation: First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Tamagawa
authors.forename: Tomiyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Maehara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yaoita
authors.forename: Yukio
authors.initials: Y
authors.lastname: Maruyama
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage*; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002932:Cineangiography; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D007269:Injections, Intra-Arterial; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D011433:Propranolol / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000502:physiology; D015016:Yohimbine / Q000008:administration & dosage
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D011799:Quinazolines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; C018176:bunazosin; D011433:Propranolol; D019331:NG-Nitroarginine Methyl Ester