Calcium and Cardiovascular Disease

Abstract

When the calcium-antagonist agents were initially used by Fleckenstein’s group, it was found that beta-adrenoceptor agonists opposed the specific action of high dose verapamil (10^-5M) in inhibiting myocardial contractility (Figure 3 and 7 in Fleckenstein, 1971). The restorative effect of isoproterenol was very similar to that of an increased extracellular calcium (Figure 6 in Fleckenstein, 1971). Thus early thinking saw calcium-antagonists and beta-antagonists as having opposite effects on trans-sarcolemmal calcium flux. Some even argued that the calcium-antagonists had beta-blocking qualities, an argument that was laid to rest when it was found that verapamil was unable to inhibit an isoproterenol-induced tachycardia or inotropic response (Nayler et al, 1968). The explanation was that verapamil could not prevent catecholamine-induced increases in the tissue level of cyclic AMP nor the beta-mediated activation of adenyl cyclase; rather, verapamil blocked the trans-sarcolemmal calcium influx provoked in K⁺ depolarized hearts by either catecholamines or by an increased external calcium (Watanabe et al, 1974).