Effects of calcium antagonists on isolated myocardial tissue and their molecular mechanism of action
Bayer, R.; Kaufmann, R.; Rodenkirchen, R.; Mannhold, R.
Herz 7(4): 203-210
1982
ISSN/ISBN: 0340-9937 PMID: 6127299 Document Number: 196865
Ca-antagonists, from the chemical point of view, are quite heterogeneous agents, which in isolated myocardial tissues exhibit rather different actions. Most have the following features in common: a negative inotropic, chronotropic and dromotropic action and smooth muscle relaxation. A frequency-dependent negative inotropic action is demonstrated, indicating the existence not only of quantitative but also qualitative effects. Correlations of negatively inotropic acting drugs with their lipophilic character demonstrate the necessity of distinguishing between specific Ca-antagonists and drugs which reduce contractile activity via a nonspecific Ca-antagonistic mode of action. Among the specific Ca-antagonists, it is obvious that they differ with respect to their molecular structure and their mode of negative inotropic and electrophysiological actions. Verapamil reduces the slow (Ca2+)-inward current predominantly at high stimulation rates. This effect can be reduced by hyperpolarizing the membrane. The action of nifedipine is not controlled by the frequency of activation and it is not affected by hyperpolarization. Most of the Ca-antagonists not only reduce slow (Ca2+)-inward current but also affect Na+ and/or K+ membrane conductance. They may be regarded to represent more than the term Ca-antagonist expresses. In man, most of the Ca-antagonists have little effect on SA[sino-atrial]-nodal frequency and AV[atrio-ventricular]-nodal conduction. In vitro experiments strongly indicate a severe impairment of both SA- and AV-nodal function. This negative chronotropic as well as dromotropic effect can be overcome by addition of isoprenaline. It may be hazardous to interrupt sympathetic regulatory mechanisms by combining Ca-antagonists with .beta.-receptor blocking agents.