Correlation between the inhibitory activities of calcium entry blockers on vascular smooth muscle constriction in vitro after K+-depolarisation and in vivo after alpha 2-adrenoceptor stimulation.

Calcium entry blockers are known to depress the maximal increase in diastolic pressure induced in pithed rats by selective alpha 2-adrenoceptor stimulation. In order to substantiate the relevance of calcium fluxes in this interaction, a correlation between the potency of calcium entry blockers in pithed rats and their calcium antagonistic potency in vitro was investigated. Accordingly, the inhibition of calcium entry blockers with respect to alpha 2-adrenoceptor-mediated vasoconstriction was quantified in terms of -log ID50 values. As a measure of calcium antagonistic potency, the inhibitory activity of a number of calcium entry blockers on K+-induced contractions of rabbit thoracic aorta strips was determined and the negative logarithms of the 50% inhibitory concentrations, -log IC50, were calculated. A highly significant linear relationship was found between the in vitro, -log IC50, and the in vivo parameter, -log ID50, of the calcium entry blockers. This result suggests a similar type of interaction for the calcium entry blockers in vivo and in vitro, i.e. inhibition of a transmembrane influx of extracellular calcium.