title: The effects of calcium antagonists on extracellular potassium accumulation during global ischaemia in isolated perfused rat hearts.
abstract: The effects of equipotent concentrations of diltiazem, verapamil, and nifedipine upon the accumulation of extracellular potassium [K+]out and the left ventricular pressure (LVP) were studied during global ischemia in isolated perfused rat hearts. Measurement of [K+]out and LVP were performed in two series of experiments. Diltiazem (2 x 10(-6), 3 x 10(-6), and 10(-5) M), verapamil (3 x 10(-8), 10(-7), and 3 x 10(-7) M), and nifedipine (3 x 10(-8), 10(-7), and 1.5 x 10(-7) M) were able to slow, in a concentration-dependent manner, the initial rate of rise of [K+]out without affecting the final plateau value of [K+]out reached at t = 5 to t = 10 minutes. Notably, at the lowest concentrations, which slightly influenced LVP diltiazem, verapamil, and to a lesser degree nifedipine, were still able to slow the rise in [K+]out. In addition, after preperfusion with low-calcium media [( Ca2+] from 1.8 to 1.3 or 0.9 mM), inducing similar negative inotropic effects as those of the calcium antagonists, the rise in [K+]out was not significantly influenced. Our data indicate that the ability to slow the rise in [K+]out is a specific characteristic of calcium antagonists that is independent of their negative inotropic effects.
authors.affiliation: Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
authors.forename: J B
authors.initials: JB
authors.lastname: Heijnis
authors.forename: R
authors.initials: R
authors.lastname: Coronel
authors.forename: P A
authors.initials: PA
authors.lastname: van Zwieten
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D004110:Diltiazem / Q000494:pharmacology; D004566:Electrodes; D005110:Extracellular Space / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D016277:Ventricular Function, Left / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D011188:Potassium