Open AccessDynamic and Kinetic Differences of the Vascular and Myocardial Effects of Calcium Antagonists in the Rat Heart
Author(s) -
F. T. M. Van Amsterdam,
M Haas,
Johan Zaagsma
Publication year - 1987
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-198705000-00011
Subject(s) - verapamil , bepridil , nifedipine , diltiazem , gallopamil , inotrope , medicine , calcium , cardiology , nimodipine , chemistry , pharmacology
We studied the effects of nifedipine, nimodipine, verapamil, D600 (gallopamil), D888 (desmethoxyverapamil), D890 (quaternized verapamil), bepridil, and diltiazem on the coronary flow and the left ventricular pressure in the retrogradely perfused paced rat heart; in addition, we investigated the time course of onset and recovery of these effects. We found a clear difference in potency order for the vascular and cardiac effects as well as widely different kinetics of coronary flow increase and negative inotropic activity. Furthermore, positive inotropism at low doses of some calcium antagonists seemed to be related to the vascular effects of these compounds. We conclude that the rat heart contains a hydrophylic and readily accessible, vascular "dihydropyridine" site and a more hydrophobic, possibly intramembraneous or intracellular, myocardial "verapamil" site with a lower accessibility for verapamil derivatives and bepridil.