Effect of calcium entry blockers and adenosine on the relaxation of large and small coronary arteries.
The mechanism(s) by which adenosine causes dilation of the vascular smooth muscle is not properly understood. Several mechanisms including the inhibition of calcium influx and intracellular translocation have been suggested for its action. This study is an attempt to further elucidate the site of action of adenosine in relation to calcium by making use of calcium entry blockers. Large (1 +/- 0.2 mm, o.d.) and small (0.5 +/- 0.2 mm, o.d.) branches of bovine left anterior descending coronary artery (LADCA) contracted with 50 mM K+ were used as a model for these studies. Concentration-response curves for various calcium entry blockers were obtained and the order of potency was found to be: D-600 greater than nifedipine greater than verapamil greater than diltiazem greater than lidoflazine for large branches and nifedipine greater than D-600 greater than verapamil greater than lidoflazine greater than diltiazem for small branches of LADCA. The concentration-response relationship for adenosine (10(-6)-10(-4) M) in the presence and absence of these drugs (10(-9)-10(-7) M) was unchanged. 8-phenyltheophylline (2 X 10(-5) M), an adenosine receptor antagonist was without an effect on the relaxations induced by various calcium entry blockers, however, it antagonized the relaxing response to adenosine. Lidoflazine at concentrations of 7 X 10(-7) M and 2 X 10(-7) M potentiated the effect of adenosine in relaxing the large and small LADCA, respectively. In summary, the data show an increased sensitivity of small coronary vessels to nifedipine, D-600 and lidoflazine. The data further suggest a different site of action for adenosine and calcium entry blockers.
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D003331:Coronary Vessels / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005711:Gallopamil / Q000494:pharmacology; D008013:Lidoflazine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D002121:Calcium Channel Blockers; D005711:Gallopamil; D013806:Theophylline; C028322:8-phenyltheophylline; D009543:Nifedipine; D008013:Lidoflazine; D000241:Adenosine