Cardiac effects of ethacrynic acid, a Na+, K+-ATPase inhibitor. 1975

D C Michaels, and E Kabela

To test hypotheses relating positive inotropic effects of cardiac glycosides (CG) to inhibitory effects on Na,K-ATPase, cardiac actions of other inhibitors were examined. Ethacrynic acid was studied using microelectrode recordings of dog Purkinje fibers (DP) and cat papillary muscle (CP), and isometric recordings of CP at Lmax stimulated at 1/sec (36.5 degrees C). Results with all doses (20-200 gamma/ml) were similar, differing only in latency. Actions of ethacrynic acid on electrical activity of DP and CP were, chronologically: increase in duration of the action potential (AP), and decrease in dV/dt, overshoot, and resting potential. In CP an initial increase (2-5 min) in contractility (10-15 percent) was followed by decreased in active tension and dP/dt with parallel increases in resting tension and duration of contraction. ATP levels were unchanged, eliminating the possibility of ethacrynic acid acting as a metabolic poison. Simultaneous recording of contractions and AP in CP showed that the positive inotropic effect was always associated with a lengthening of the AP. In a series of CP, ouabain (2 gamma/ml) always increased contractility when ethacrynic acid had already reduced it by 75 percent. These results suggest that Na,K-ATPase inhibition is not responsible for the inotropic effects of CG.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010042 Ouabain A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE. Acocantherin,G-Strophanthin,Acolongifloroside K,G Strophanthin
D010210 Papillary Muscles Conical muscular projections from the walls of the cardiac ventricles, attached to the cusps of the atrioventricular valves by the chordae tendineae. Muscle, Papillary,Muscles, Papillary,Papillary Muscle
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D011690 Purkinje Fibers Modified cardiac muscle fibers composing the terminal portion of the heart conduction system. Purkinje Fiber,Fiber, Purkinje,Fibers, Purkinje
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D004976 Ethacrynic Acid A compound that inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. This compound has been classified as a loop or high ceiling diuretic. Edecrin,Etacrynic Acid,Ethacrinic Acid,Ethacrynate Sodium,Ethacrynic Acid, Sodium Salt,Hydromedin,Acid, Etacrynic,Acid, Ethacrinic,Acid, Ethacrynic,Sodium, Ethacrynate
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts

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