EXPERIMENTAL STUDY
Influence of propranolol, enalaprilat, verapamil, and caffeine on adenosine A2A-receptor–mediated coronary vasodilation
Laurent M. Riou, PhD*,
Mirta Ruiz, MD*,
Jayson M. Rieger, PhD*,
Timothy L. Macdonald, PhD*,
Denny D. Watson, PhD*,
Joel Linden, PhD*,
George A. Beller, MD, FACC* and
David K. Glover, ME*,*
* Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia, USA
Manuscript received March 28, 2002;
revised manuscript received June 13, 2002,
accepted July 24, 2002.
* Reprint requests and correspondence: David K. Glover, ME, Cardiovascular Division, University of Virginia Health Sciences System, P.O. Box 800500, Charlottesville, Virginia 22908-0500, USA.
dglover{at}virginia.edu
OBJECTIVES: The study was done to determine the effects of propranolol, enalaprilat, verapamil, and caffeine on the vasodilatory properties of the adenosine A2A-receptor agonist ATL-146e (ATL).
BACKGROUND: ATL is a new adenosine A2A-receptor agonist proposed as a vasodilator for myocardial stress perfusion imaging. Beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium blockers are commonly used for the treatment of coronary artery disease (CAD), and their effect on ATL-mediated vasodilation is unknown. Dietary intake of caffeine is also common.
METHODS: In 19 anesthetized, open-chest dogs, hemodynamic responses to bolus injections of ATL (1.0 µg/kg) and adenosine (60 µg/kg) were recorded before and after administration of propranolol (1.0 mg/kg, ATL only), enalaprilat (0.3 mg/kg, ATL only), caffeine (5.0 mg/kg, ATL only), and verapamil (0.2 mg/kg bolus, ATL and adenosine).
RESULTS: Neither propranolol nor enalaprilat attenuated the ATL-mediated vasodilation (225 ± 86% and 237 ± 67% increase, respectively, p = NS vs. control). Caffeine had an inhibitory effect (97 ± 28% increase, p < 0.05 vs. control). Verapamil blunted both ATL- and adenosine-induced vasodilation (63 ± 20% and 35 ± 7%, respectively, p < 0.05 vs. baseline), and also inhibited the vasodilation induced by the adenosine triphosphate-sensitive potassium (KATP) channel activator pinacidil.
CONCLUSIONS: Beta-blockers and ACE inhibitors do not reduce the maximal coronary flow response to adenosine A2A-agonists, whereas verapamil attenuated this vasodilation through inhibition of KATP channels. The inhibitory effect of verapamil and KATP channel inhibitors like glybenclamide on pharmacologic stress using adenosine or adenosine A2A-receptor agonists should be evaluated in the clinical setting to determine their potential for reducing the sensitivity of CAD detection with perfusion imaging.
|
Abbreviations and Acronyms
| | ACE | | angiotensin-converting enzyme | | CAD | | coronary artery disease | | CFR | | coronary flow reserve | | dP/dt | | peak positive first derivative of left ventricular pressure with respect to time | | HR | | heart rate | | IV | | intravenous | | KATP | | adenosine triphosphate-sensitive potassium | | LAD | | left anterior descending coronary artery | | LAP | | left atrial pressure | | LCx | | left circumflex coronary artery | | MAP | | mean arterial pressure | | NO | | nitric oxide |
|
This article has been cited by other articles:
|
|
|
|
 
E. Reyes, C. Y. Loong, M. Harbinson, J. Donovan, C. Anagnostopoulos, and S. R. Underwood
High-Dose Adenosine Overcomes the Attenuation of Myocardial Perfusion Reserve Caused by Caffeine
J. Am. Coll. Cardiol.,
December 9, 2008;
52(24):
2008 - 2016.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J. Zoghbi, T. Htay, R. Aqel, L. Blackmon, J. Heo, and A. E. Iskandrian
Effect of Caffeine on Ischemia Detection by Adenosine Single-Photon Emission Computed Tomography Perfusion Imaging
J. Am. Coll. Cardiol.,
June 6, 2006;
47(11):
2296 - 2302.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Voci, F. Pizzuto, and F. Romeo
Coronary flow: a new asset for the echo lab?
Eur. Heart J.,
November 1, 2004;
25(21):
1867 - 1879.
[Full Text]
[PDF]
|
|
|
|
