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EXPERIMENTAL STUDY

Influence of propranolol, enalaprilat, verapamil, and caffeine on adenosine A_2A-receptor–mediated coronary vasodilation

^* 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 A_2A-receptor agonist ATL-146e (ATL).

BACKGROUND: ATL is a new adenosine A_2A-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 (K_ATP) channel activator pinacidil.

CONCLUSIONS: Beta-blockers and ACE inhibitors do not reduce the maximal coronary flow response to adenosine A_2A-agonists, whereas verapamil attenuated this vasodilation through inhibition of K_ATP channels. The inhibitory effect of verapamil and K_ATP channel inhibitors like glybenclamide on pharmacologic stress using adenosine or adenosine A_2A-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

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