Summary
The mechanism of inotropic actions of vanadate was studied in isolated, electrically stimulated atrial and ventricular muscle preparations of rat or guinea-pig heart. Vanadate produced a negative inotropic effect in guinea-pig left atrial preparations associated with a marked shortening of the action potential plateau. In guinea-pig papillary muscle, or rat atrial or ventricular muscle preparations, vanadate produced a positive inotropic effect, which was not affected by either propranolol, phentolamine or metiamide. The positive inotropic effect was observed when action potential duration was either increased or decreased. Inotropic concentrations of vanadate failed to significantly alter the ouabain-sensitive 86Rb+-uptake, an estimate of sodium pump activity, or tissue concentration of cyclic AMP in electrically stimulated preparations. In partially depolarized rat atrial preparations in which fast sodium channels were inactivated in the presence of a high concentration of K+ (22 mmol/l), vanadate restored electrical activity (calcium-dependent action potentials) and the contraction, similar to isoproterenol. This action of vanadate was abolished by Mn2+, a slow channel inhibitor, but not by tetrodotoxin. The characteristic of vanadate- and isoproterenol-restored preparations, however, were substantially different. Moreover, vanadate failed to restore the contraction or action potential in partially depolarized guinea pig atrial preparations unlike isoproterenol. These results indicate that vanadate may either enhance or inhibit slow channels in cardiac muscle.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akera T, Takeda K, Yamamoto S, Brody TM (1979) Effects of vanadate on Na+, K+-ATPase and on the force of contraction in guinea-pig hearts. Life Sci 25:1803–1812
Balfour WE, Grantham JJ, Glynn IM (1978) Vanadate-stimulated natriuresis. Nature (Lond) 275:768
Beauge LA, Glynn IM (1977) A modifier of (Na++K+)-ATPase in commercial ATP. Nature (Lond) 268:355–356
Beauge LA, Glynn IM (1978) Commercial ATP containing traces of vanadate alters response of (Na++K+)-ATPase to external potassium. Nature (Lond) 272:551–552
Bentfeld M, Lüllmann H, Peters T, Proppe D (1977) Interdependence of ion transport and the action of ouabain in heart muscle. Br J Pharmacol 61:19–27
Borchard U, Fox AAL, Greeff K, Schlieper P (1979) Negative and positive inotropic action of vanadate on atrial and ventricular myocardium. Nature (Lond) 279:339–341
Brown BS, Polson JB, Krzanowski JJ (1979) Methacholine-induced attenuation of methylisobutylxanthine- and isoproterenol-elevated cyclic AMP levels in isolated rat atria. Biochem Pharmacol 28:948–951
Cantley LC Jr, Josephson L, Warner R, Yanagisawa M, Lechene C, Guidotti G (1977) Vanadate is a potent (Na,K)-ATPase inhibitor found in ATP derived from muscle. J Biol Chem 252:7421–7423
Cantley LC, Resh MD, Guidotti G (1978) Vanadate inhibits red-cell (Na++K+)-ATPase from cytoplasmic side. Nature (Lond) 272:552–554
Chubb JM, Bennett JL, Akera T, Brody TM (1978) Effects of praziquantel, a new anthelmintic, on electromechanical properties of isolated rat atria. J Pharmacol Exp Ther 207:284–293
Erdmann E, Krawietz W, Philipp G, Hackbarth I, Schmitz W, Scholz H (1979) Stimulatory effect of vanadate on (Na++K+)-ATPase activity and on 3H-ouabain-binding in a cat heart cell membrane preparation. Nature (Lond) 278:459–461
Frank M, Akera T, Brody TM (1976) Effects of ryanodine on the contractile force of potassium-depolarized hearts. Res Comm Chem Pathol Pharmacol 15:511–523
Grupp G, Grupp I, Johnson CL, Wallick ET, Schwartz A (1979) Effects of vanadate on cardiac contraction and adenylate cyclase. Biochem Biophys Res Commun 88:440–447
Hackbarth I, Schmitz W, Scholz H, Erdmann E, Krawietz W, Philipp G (1978) Positive inotropism of vanadate in cat papillary muscle. Nature (Lond) 275:67
Hackbarth I, Schmitz W, Scholz H, Wetzel E, Erdmann E, Krawietz W, Philipp G (1980) Stimulatory effect of vanadate on cyclic AMP levels in cat papillary muscle. Biochem Pharmacol 29:1429–1432
Josephson L, Cantley LC Jr (1977) Isolation of a potent (Na−K)-ATPase inhibitor from striated muscle. Biochemistry 16:4572–4578
Karlish SJD, Beauge LA, Glynn IM (1979) Vanadate inhibits (Na++K+)-ATPase by blocking a conformational change of the unphosphorylated form. Nature (Lond) 282:333–335
Krawietz W, Werdan K, Erdmann E (1979) Stimulatory effect of vanadate on the adenylate cyclase of cardiac tissue. Biochem Pharmacol 28:2517–2520
Ku D, Akera T, Pew CL, Brody TM (1974) Cardiac glycosides: Correlation among Na+, K+-ATPase, sodium pump and contractility in the guinea-pig heart. Naunyn-Schmiedeberg's Arch Pharmacol 285:185–200
Levi R, Allan G, Zavecz JH (1976) Cardiac histamine receptors. Fed Proc 35:1942–1947
Mascher D (1970) Electrical and mechanical responses from ventricular muscle fibers after inactivation of the sodium carrying system. Pflügers Arch 317:359–372
Nabata H (1977) Effects of calcium-antagonistic coronary vasodilators on myocardial contractility and membrane potentials. Jpn J Pharmacol 27:239–249
Pappano AJ (1970) Calcium-dependent action potentials produced by catecholamines in guinea pig atrial muscle fibers depolarized by potassium.Circ Res 27:379–390
Post RL (1979) A model for regulation of vanadate inhibition of (Na,K)-ATPase by reduction. Fed Proc 38:242
Rougier Q, Vassort G, Garnier D, Gargouil YM, Coraboeuf E (1969) Existence and role of a slow inward current during the frog atrial action potential. Pflügers Arch 308:91–110
Schlieper P, Borchard U, Fox AAL, Greeff K (1979) Positive and negative inotropic effects of vanadate on isolated rat and guinea-pig atria. Naunyn-Schmiedeberg's Arch Pharmacol 308:R34
Schmitz W, Hackbarth I, Scholz H (1979) Effect of vanadate on force of contraction in mammalian cardiac muscle. Naunyn-Schmiedeberg's Arch Pharmacol 307:R37
Schwabe U, Puchstein C, Hannemann H, Söchtig E (1979) Activation of adenylate cyclase by vanadate. Nature (Lond) 277:143–145
Steiner AL, Pagliara AS, Chase LR, Kipnis DM (1972) Radioimmunoassay for cyclic nucleotides. J Biol Chem 247:1114–1120
Takeda K, Yamamoto S, Akera T, Brody TM (1979) Effects of vanadate on contractility, action potential and 86Rb uptake in atrial and ventricular muscle of rat and guinea-pig. Pharmacologist 21:276
Temma K, Akera T, Brody TM (1977) Hydroxylated chloropromazine metabolites: Positive inotropic action and the release of catecholamines. Mol Pharmacol 13:1076–1085
Thyrum PT (1974) Inotropic stimuli and systolic transmembrane calcium flow in depolarized guinea-pig atria. J Pharmacol Exp Ther 188:166–179
Verma SC, McNeill JH (1977) Cardiac histamine receptors: Differences between left and right atria and right ventricle. J Pharmacol Exp Ther 200:352–362
Wallick ET, Lane LK, Schwartz A (1979) Regulation by vanadate of ouabain binding to (Na+,K+)-ATPase. J Biol Chem 254:8107–8109
Werdan K, Bauriedel G, Bozsik M, Krawietz W, Erdmann E (1980) Effects of vanadate in cultured rat heart muscle cells: Vanadate transport, intracellular binding and vanadate-induced changes in beating and in active cation flux. Biochim Biophys Acta 597:364–383
Yamamoto S, Akera T, Brody TM (1979) Sodium influx rate and ouabain-sensitive rubidium uptake in isolated guinea pig atria. Biochim Biophys Acta 555:270–284
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Takeda, K., Akera, T., Yamamoto, S. et al. Possible mechanisms for inotropic actions of vanadate in isolated guinea pig and rat heart preparations. Naunyn-Schmiedeberg's Arch. Pharmacol. 314, 161–170 (1980). https://doi.org/10.1007/BF00504533
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00504533