Synergistic effect of nifedipine and propranolol on adenosine (catabolite) release from ischemic rat heart

Abstract

Both nifedipine a calcium antagonist, and propranolol a beta-adrenergic blocker, are used as protective agents of the ischemic myocardium. In the clinical setting, the combination of the two drugs is used successfully although several case reports indicate potential dangers of the combination. For this reason we decided to study the combined effect of nifedipine and DL-propranolol in the isolated rat heart made ischemic for a short period of time. Apex displacement was taken as a measure of contractility. Release of the AMP catabolites adenosine, inosine, (hypo)xanthine and uric acid was used as a marker of ATP breakdown. Contractility during ischemia was not affected by the drugs. DL-Propranolol (30 or 150 micrograms/l) had no effect on ischemic myocardial purine release, while nifedipine (15 micrograms/l) reduced purine release during ischemia by 33% (P less than 0.02). The combination of 15 micrograms/l nifedipine and 150 micrograms/l DL-propranolol decreased purine release by 53% (P less than 0.005 vs. nifedipine). We conclude from these results that propranolol has a synergistic effect, adding to the beneficial action of nifedipine on ischemic myocardium.