Increased activity of sarcolemmal (Na+K+)-ATPase is involved in the late cardioprotective action of 7-oxo-prostacyclin.
The delayed effects of 7-oxo-prostacyclin, protecting the heart against extrasystoles, ventricular fibrillation, and cardiac arrest induced by high doses of ouabain or in ischemia and postischemic reperfusion, have already been described; but little is known about the molecular mechanisms involved. In this study, 50 micrograms.kg-1 7-oxo-prostacyclin administered intramuscularly significantly stimulated the activity of (Na+K+)-ATPase in rat heart sarcolemma 24 and 48 hours after application (p less than 0.01 and p less than 0.001, respectively). Kinetic analysis revealed a mixed type of stimulation of ATPase activity, with increased Vmax and decreased Km values. Cycloheximide (1 mg.kg-1) applied together with 7-oxo-prostacyclin, significantly antagonized the stimulatory effect of 7-oxo-prostacyclin, and had a modulatory effect on the kinetics of the (Na+K+)-ATPase both 24 and 48 hours after administration. The results show that protein synthesis is involved in the mechanism of the increase in enzyme activity.
Dzurba
A
A
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Czechoslovakia.
Ziegelhoeffer
A
A
Breier
A
A
Vrbjar
N
N
Szekeres
L
L
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology*; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
C033705:7-oxoprostaglandin I2; D011464:Epoprostenol; D000254:Sodium-Potassium-Exchanging ATPase