A pharmacological analysis of the possible role of vasoactive mediators in compensatory coronary blood flow.
BACKGROUND
Coronary blood flow in one (circumflex) branch of the left coronary artery increases when an adjacent (left anterior descending [LAD]) branch is occluded for periods of between 1 min and 25 min.


OBJECTIVE
To examine the possible role of the myocardial release of vasoactive substances in such 'compensatory blood flow' increase by the classical pharmacological approach of inhibition of synthesis, or blockade at the receptor level, of the most likely mediators.


METHODS
In pentobarbitone anesthetized, thoracotomized dogs, coronary blood flow changes were measured in both the LAD (using a Doppler flow probe) and the left circumflex (using an electromagnetic flow probe) coronary arteries.


RESULTS
The flow increase during 5 min occlusions of the LAD coronary artery was unaffected by blockade of adenosine receptors by 8-sulfophenyltheophylline, inhibition of prostanoid synthesis by sodium meclofenamate or celecoxib, blockade of bradykinin B(1) receptors by icatibant, inhibition of nitric oxide synthesis by N(omega)-nitro-L-arginine methyl ester (L-NAME), inhibition of guanylyl cyclase by methylene blue, or opening (using diazoxide) and closing (using glibenclamide or 5-hydroxydecanote) of ATP-dependent K(+) channels. Neither dual blockade with L-NAME and glibenclamide, or meclofenamate and 5-hydroxydecanote, nor triple blockade with L-NAME, glibenclamide and 8-sulfophenyltheophylline, modified the blood flow response. However, it was greatly reduced (60%) by metoprolol.


CONCLUSIONS
These results suggest that coronary vascular beta(1)-adrenoceptors are involved in 'compensatory' vasodilation, whereas bradykinin, nitric oxide, prostanoids and ATP-dependent K(+) channels are seemingly not required for this flow increase.
Parratt
James R
JR
Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical and Pharmaceutical Center, University of Szeged, Szeged, Hungary.
Végh
Agnes
A