title: Selective action of metoprolol to attenuate regadenoson-induced tachycardia in conscious dogs.
abstract: BACKGROUND
  Regadenoson is a coronary vasodilator that causes tachycardia via activation of the sympathetic nervous system. We determined whether β(1)-adrenergic blockade can attenuate tachycardia without significantly reducing coronary vasodilation induced by regadenoson.
  
  
  RESULTS
  Hemodynamics and coronary blood flow (CBF) were measured in conscious dogs. Baseline CBF and heart rate (HR) were 42 ± 2 mL/min and 87 ± 8 bpm (mean ± SEM), respectively. Regadenoson (1, 2.5, and 5 μg/kg) increased peak CBF by 129 ± 10, 149 ± 7, and 174 ± 10 mL/min and HR by 48 ± 6, 67 ± 5, and 85 ± 11 bpm, respectively, (all P < .05 vs baseline). In the presence of metoprolol (1.5 mg/kg), the peak increases in CBF caused by these three doses of regadenoson were reduced by only 11 ± 7%, 10 ± 4%, and 21 ± 2% (P = NS, <.05, and <.05 vs regadenoson alone), respectively, whereas the regadenoson-induced tachycardia was significantly reduced by 55 ± 8%, 55 ± 4%, and 52 ± 5% (all P < .05). In the presence of metoprolol, the duration of the regadenoson-induced increase in CBF was reduced, but the duration of the 2-fold increase in CBF caused by 5 μg/kg regadenoson was still nearly 6 minutes.
  
  
  CONCLUSIONS
  β(1)-Adrenergic blockade with metoprolol attenuated the regadenoson-induced increase in HR more than the increase in CBF.
authors.affiliation: Department of Biology, Gilead Sciences Palo Alto, 1651 Page Mill Road, Palo Alto, CA 94304, USA. gong.zhao@gilead.com
authors.forename: Gong
authors.initials: G
authors.lastname: Zhao
authors.forename: Suhua
authors.initials: S
authors.lastname: Zhang
authors.forename: John C
authors.initials: JC
authors.lastname: Shryock
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Xu
authors.forename: Manuel
authors.initials: M
authors.lastname: Ochoa
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hintze
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage*; D011687:Purines / Q000009:adverse effects*; D011720:Pyrazoles / Q000009:adverse effects*; D013610:Tachycardia / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects
chemical_list: D000889:Anti-Arrhythmia Agents; D011687:Purines; D011720:Pyrazoles; D014665:Vasodilator Agents; C430916:regadenoson; D008790:Metoprolol