Effects of 2-methyl-1,4-naphthoquinone (menadione) on myocardial contractility and cardiac sarcoplasmic reticulum Ca-ATPase
- 1 April 1989
- journal article
- research article
- Published by Springer Science and Business Media LLC in Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie
- Vol. 339 (4), 448-455
- https://doi.org/10.1007/bf00736060
Abstract
(1) In electrically driven guinea-pig left atria, menadione (2-methyl-1,4-naphthoquinone) (1 to 20 μmol/1) and menadione sodium bisulfate (30 to 200 μmol/1) produced marked positive inotropic effects. Endogenously released catecholamines and histamine contributed to 80–85% of the effect, the residual 15–20% appearing as a direct effect. (2) In electrically driven guinea-pig ventricular strips, low micromolar concentrations of menadione (0.05 to 0.3 μmol/1) exerted a catecholamine-mediated small positive inotropic effect. (3) In both myocardial preparations, the increase in force of contraction was followed by a non-reversible rise of resting force. In its effects on cardiac contractility menadione resembled the thiol group blocking agent pchloromercuribenzoate and H2O2. Pretreatment of atria with glutathione prevented the increase in resting force, while dithiothreitol only slightly delayed it. By contrast, the pretreatment with the NAD(P)H-quinone reductase (DT-diaphorase) inhibitor, dicumarol, markedly increased the rate of appearance of the toxic effect of menadione. (4) Among enzymatic and transport systems involved in the onset and control of cardiac contractility, sarcoplasmic reticulum Ca-ATPase was significantly inhibited by menadione after a long contact time. The inhibition was concentration-dependent and persistent, and was antagonized by addition of glutathione. (5) On the basis of these results, the increase in resting force caused by menadione appears to be related to an impairment of the thiol groups of proteins (Ca-ATPase), presumably caused by the drug per se.Keywords
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