Nifedipine and experimental cardioprotection.
Experimental studies using animal models designed to mimic the effect of ischemia and postischemic reperfusion have provided data indicating that the calcium antagonists might be cardioprotective. The laboratory studies have indicated consistently, however, that the timing of such drug administration is of critical importance. In the case of nifedipine (a dihydropyridine-based calcium antagonist), the laboratory studies have shown that when used prophylactically it has a protective effect during short (as in the "stunned heart") and long episodes (greater than 30 minutes) of ischemia. This protection has been quantitated in a variety of ways, including preservation of left ventricular function. A complete understanding of whether and how calcium antagonists can be used to protect the myocardium requires further detailed knowledge of not only of the voltage-activated calcium channel and its binding sites, but also of the sequence of events triggered by ischemia and reperfusion. Recent data from our laboratories indicate that cardiac membranes contain specific binding sites for the novel, endothelial-derived vasoconstrictor peptide, ET, and that the density of these sites increases during ischemia. ET promotes Ca2+ influx through the voltage-sensitive channels by a mechanism that does not involve a direct interaction with the dihydropyridine (DHP)-sensitive binding sites. Nevertheless, the ET-induced Ca2+ influx is attenuated by the dihydropyridine-based calcium channel blockers.
Nayler
W G
WG
Department of Medicine, University of Melbourne, Austin Hospital, Victoria, Australia.
Liu
J J
JJ
Panagiotopoulos
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000188:drug therapy / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D006321:Heart / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D009206:Myocardium / Q000648:ultrastructure; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D016232:Endothelins; D014280:Triglycerides; D002784:Cholesterol; D009543:Nifedipine; D002118:Calcium