Caffeine attenuates the duration of coronary vasodilation and changes in hemodynamics induced by regadenoson (CVT-3146), a novel adenosine A2A receptor agonist.
Effects of caffeine on regadenoson-induced coronary vasodilation and changes in hemodynamics were examined in conscious dogs. Sixteen dogs were chronically instrumented for measurements of coronary blood flow (CBF), mean arterial pressure (MAP), and heart rate (HR). Regadenoson (5 microg/kg, IV) increased CBF from 34 +/- 2 to 191 +/- 7 mL/min. The duration of the 2-fold increase in CBF was 515 +/- 71 seconds. Regadenoson decreased MAP by 15 +/- 2% and increased HR by 114 +/- 14%. Regadenoson-induced maximum increases in CBF were not significantly lower in the presence of caffeine at 1, 2, 4, and 10 mg/kg (2 +/- 3, 0.7 +/- 3, 16 +/- 5, and 13 +/- 8%, respectively; all P > 0.05). Caffeine at 1, 2, 4, and 10 mg/kg significantly decreased the duration of the 2-fold increase in CBF induced by regadenoson by 17% +/- 4%, 48% +/- 8%, 62% +/- 5%, and 82% +/- 5%, respectively (all P < 0.05). Caffeine at 4 and 10 mg/kg significantly attenuated the effects of regadenoson on MAP and HR. The results indicate that 1 to 10 mg/kg caffeine dose-dependently reduced the duration, but not the peak increase of CBF caused by 5 microg/kg regadenoson.
Zhao
Gong
G
Department of Pharmacology and Preclinical Development, CV Therapeutics, Inc., Palo Alto, California, USA. gong.zhao@cvt.com
Messina
Eric
E
Xu
Xiaobin
X
Ochoa
Manuel
M
Sun
Hai-Ling
HL
Leung
Kwan
K
Shryock
John
J
Belardinelli
Luiz
L
Hintze
Thomas H
TH
D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D008297:Male; D011687:Purines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
D058908:Adenosine A2 Receptor Agonists; D011687:Purines; D011720:Pyrazoles; C430916:regadenoson; D002110:Caffeine