Protection by verapamil and nifedipine against ischaemia-induced loss of [3H]-(+)-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 [3H]-(+)-PN 200-110 and [3H]-(-)-devapamil (desmethoxyverapamil or D888) in rat heart membranes. The hearts were perfused in the Langendorff-mode and pretreated with 1 mumol/l verapamil, 30 nmol/l and 1 mumol/l nifedipine. After 60 min of global ischaemia in the absence of drugs, we found a reduction of [3H]-(+)-PN 200-110 binding sites, without changes in the equilibrium dissociation binding constant (Kd). After the subsequent reperfusion maximum specific binding (Bmax) was further reduced, whereas the Kd remained constant. [3H]-devapamil binding sites were influenced to a lower extend and showed only a decrease in Bmax at reperfusion. Pretreatment with 1 mumol/l verapamil completely prevented the changes which were observed for [3H]-(+)-PN 200-110. Pretreatment with a low, vasodilating concentration (30 nmol/l) of nifedipine displayed selective protection against the extra reduction in Bmax 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.
van Amsterdam
F T
FT
Department of Pharmacology and Therapeutics, University of Groningen, The Netherlands.
van Amsterdam-Magnoni
M S
MS
Haas
M
M
Punt
N C
NC
Zaagsma
J
J
D000818:Animals; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels; D003327:Coronary Disease / Q000378:metabolism*; D066298:In Vitro Techniques; D017275:Isradipine; D007700:Kinetics; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D010069:Oxadiazoles / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014700:Verapamil / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010069:Oxadiazoles; D011978:Receptors, Nicotinic; D014700:Verapamil; D009543:Nifedipine; C055885:devapamil; D017275:Isradipine