Influence of nifedipine on systemic and regional hemodynamics during adenosine-induced hypotension in dogs

Previous pharmacologic studies indicating competitive interactions between adenosine and nifedipine at the adenosine vascular receptor suggest that adenosine may be a less effective hypotensive drug after pretreatment with nifedipine. This hypothesis was tested in 18 pentobarbital-anesthetized, open-chest dogs by evaluating the hypotensive effects and regional hemodynamic responses to 60-minute intravenous adenosine infusions before and after bolus injection of nifedipine (20 micrograms/kg, IV). Regional blood flow was measured with 15-microns radioactive microspheres. Before nifedipine, infusion of adenosine at a rate of 126 +/- 30 mumol/min caused a 50% reduction in mean aortic pressure that in the presence of no change in aortic blood flow was attributable to a proportional decrease in systemic vascular resistance. These systemic effects were associated with heterogeneous changes in regional blood flow; blood flow decreased in the renal cortex (-68%), pancreas (-50%), spleen (-77%), and skin (-61%); increased in the left (+112%) and right (+265%) ventricular myocardium; and did not change significantly in the duodenum, liver, skeletal muscle, or brain. Nifedipine did not alter the dose requirement or time course of the adenosine-induced hypotensive response or affect the associated systemic hemodynamic changes. Furthermore, nifedipine caused only minor alterations in the regional blood flow changes during adenosine-induced hypotension. Apparently the high plasma levels of adenosine required for controlled hypotension in the present study were sufficient to overcome the blocking influence of nifedipine at the adenosine vascular receptor. The study demonstrates that the hypotensive action of adenosine remains unimpaired after pretreatment with nifedipine.