Protection by verapamil and nifedipine against ischaemia-induced loss of [H]-(+)-PN 200-110 binding sites in the rat heart.

We have studied the effects of 60 min global ischaemia and 30 min of subsequent reperfusion on the binding of [H]-(+)-PN 200−110 and [H]-(−)-devapamil (desmethoxyverapamil or D888) in rat heart membranes. The hearts were perfused in the Langendorff-mode and pretreated with 1 μmol/l verapamil, 30 nmol/l and 1 μmol/l nifedipine. After 60 min of global ischaemia in the absence of drugs, we found a reduction of [H]-(+)-PN 200-110 binding sites, without changes in the equilibrium dissociation binding constant ( K). After the subsequent reperfusion maximum specific binding ( B) was further reduced, whereas the K remained constant. [H]-devapamil binding sites were influenced to a lower extend and showed only a decrease in B at reperfusion. Pretreatment with 1 μmol/l verapamil completely prevented the changes which were observed for [H]-(+)-PN 200-110. Pretreatment with a low, vasodilating concentration (30 nmol/l) of nifedipine displayed selective protection against the extra reduction in B which was observed during reperfusion. It is concluded that calcium antagonists show protection against the ischaemia-induced loss of dihydropyridine binding sites in relation to their negative inotropic, energy-saving activity. Furthermore, nifedipine at low, vasodilating but not negative inotropic concentrations protects against further reperfusion-induced injury, which protection may be related to an improved flow during reperfusion. [ABSTRACT FROM AUTHOR]