Summary
In order to determine whether the positive inotropic action of cardiac glycosides is related to the inhibition of sodium pump activity, the actions of known inhibitors:N-ethylmaleimide,p-chloromercuribenzoate (PCMB),p-chloromercuribenzene sulfonic acid (PCMBS) and digitoxin, were studied in isolated guinea pig hearts. In electrically driven left atrial preparations, all these agents increased isometric contractile force. The inotropic effect ofN-ethylmaleimide was only partially reduced in the presence of propranolol or by reserpine pretreatment, whereas the inotropic effects of PCMB and PCMBS were unaffected by reserpine pretreatment. (±)-Propranolol markedly delayed the development of the inotropic action of PCMB and PCMBS without affecting the magnitude of the peak inotropic response. Similar effect was observed with (+)-propranolol indicating that the delayed development of the inotropic action is probably due to the action of propranolol unrelated to β-adrenergic blockade. Among sulfhydryl blocking agents, the development of the inotropic effects was fastest withN-ethylmaleimide and slowest with PCMBS. Effects of these sulfhydryl inhibitors on resting potential and action potential were unrelated to the inotropic action. These agents caused a decrease in ouabain-sensitive86Rb uptake, an estimate of sodium pump activity, in sodium-loaded ventricular slices obtained from drug-perfused Langendorff preparations. Quantitative comparisons between the degree of inotropic response and sodium pump inhibition caused by these agents were not possible because of the difference in experimental conditions. These results, however, are consistent with the hypothesis that Na+, K+-ATPase inhibitors cause positive inotropic effects associated with sodium pump inhibition.
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Supported by U.S. Public Health Service Grants HL-16052 and HL-16788 and a grant from the National Science Foundation, BMS 74-19512
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Temma, K., Akera, T., Ku, D.D. et al. Sodium pump inhibition by sulfhydryl inhibitors and myocardial contractility. Naunyn-Schmiedeberg's Arch. Pharmacol. 302, 63–71 (1978). https://doi.org/10.1007/BF00586599
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DOI: https://doi.org/10.1007/BF00586599