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Blockade of nucleoside transport is required for delivery of intraarterial adenosine into the interstitium: relevance
Alfredo Gamboa1, Andrew C Ertl, Fernando Costa
1Department of Medicine, Vanderbilt University, Nashville, Tenn 37212, USA.
Circulation
|November 19, 2003
Summary
Intravascular adenosine fails to precondition the heart due to poor delivery. Blocking nucleoside transporters with dipyridamole enhances adenosine delivery and vasodilation, improving therapeutic potential.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Cellular Transport Mechanisms
Background:
- Adenosine mediates preconditioning but its therapeutic use is limited.
- Endothelial nucleoside transporters may hinder adenosine delivery to the myocardium.
- Dipyridamole is a nucleoside transporter blocker.
Purpose of the Study:
- To test if endothelial nucleoside transporters impede adenosine delivery.
- To determine if dipyridamole can overcome this barrier.
- To investigate adenosine's role in therapeutic preconditioning.
Main Methods:
- Healthy volunteers received brachial artery infusions of adenosine with or without intravenous dipyridamole.
- Forearm blood flow (FBF) and interstitial adenosine levels were monitored.
- Microdialysis probes measured adenosine concentration in forearm muscle.
Main Results:
- Adenosine induced significant forearm vasodilation but did not increase interstitial adenosine levels.
- Dipyridamole enhanced resting interstitial adenosine concentrations.
- Dipyridamole potentiated adenosine-induced vasodilation and increased interstitial adenosine delivery.
Conclusions:
- Intravascular adenosine's poor interstitial delivery limits its effectiveness for myocardial preconditioning.
- Blocking nucleoside transporters with dipyridamole improves adenosine delivery.
- Dipyridamole represents a strategy to enhance adenosine's therapeutic effects.
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