Amiloride: effects on myocardial force of contraction, sodium pump and Na+/Ca2+ exchange.
The direct effects of amiloride on myocardial contractility were examined in electrically stimulated left atrial muscle of guinea-pig heart. Amiloride (0.3 to 1.5 mM) produced a positive inotropic effect which, at higher concentrations, was followed by a decline in developed tension. These effects were not accompanied by contracture or arrhythmia and were not affected by a combination of phentolamine, nadolol, cimetidine, tripelennamine and atropine. The above concentrations of amiloride prolonged the action potential duration during the development of the positive inotropic effect; however, no further change in the action potential duration was observed during the decline in developed tension caused by high concentrations of amiloride. Myocardial membrane Na,K-ATPase, ouabain-sensitive 86Rb+ uptake and Na+-dependent Ca2+ efflux from sarcolemmal membrane vesicles were all inhibited by amiloride. The positive inotropic effect of the agent is reduced and the negative inotropic action is enhanced in low Na+ solutions, i.e., under conditions likely to favor Ca2+ influx via Na+/Ca2+ exchange. These results suggest that amiloride, under the present conditions, has a complex interaction with cardiac muscle fibers. Amiloride may produce its inotropic effects in guinea-pig atrial muscle by several mechanisms including sodium pump inhibition, Na+/Ca2+ exchange inhibition, prolongation of the action potential duration, and/or actions such as Na+/H+ exchange inhibition which were not directly addressed in this study.
R H
RH
Kennedy
J R
JR
Berlin
Y C
YC
Ng
T
T
Akera
T M
TM
Brody
D000200:Action Potentials / Q000187:drug effects; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004558:Electric Stimulation; D005110:Extracellular Space / Q000378:metabolism; D006168:Guinea Pigs; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D011868:Radioisotopes; D012413:Rubidium / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
D002316:Cardiotonic Agents; D007473:Ion Channels; D011868:Radioisotopes; D010042:Ouabain; D000584:Amiloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D002118:Calcium