Coronary interactions between nifedipine and adenosine in the intact dog heart.

Coronary vascular interactions between adenosine and the calcium entry blocker, nifedipine were studied in the open-chest, blood-perfused dog heart. Adenosine was administered either as a constant intra-coronary infusion or released endogenously during brief occlusions of the left anterior descending (LAD) coronary artery. Nifedipine was administered in therapeutic concentrations as a single i.v. bolus via the femoral vein. Prior to nifedipine treatment, adenosine (1.2 mumol/kg per min) produced a significant (P less than 0.05) 2-3 fold increase in LAD flow. This response was reduced markedly (P less than 0.05) in a dose-dependent manner by nifedipine (6-20 microgram/kg). Following administration of an average dose of 11 microgram/kg nifedipine, adenosine (1.2 mumol/kg per min) failed to elevate LAD flow significantly. Further, reactive hyperemia, produced by releasing a 30-s occlusion of the LAD, was significantly attenuated by these same nifedipine concentrations. The nifedipine-mediated attenuation could be partially overcome by prolonging the period of occlusion (60 s), or by increasing the rate of adenosine infusion. These results could not be accounted for by a nifedipine-mediated alteration of hemodynamics and suggest the possibility of pharmacological competition between adenosine and nifedipine at a vascular smooth muscle receptor.