Effect of prostaglandins on rat heart sarcolemmal ATPases

The ability of prostaglandins (PG) D2, E1, E2, F2α and I2 (2.8 × 10−11 M to 2.8 × 10−7 M) to modify Ca2+, Mg2+ and (Na+ + K+)-ATPase activities of rat heart sarcolemmal membrane fractions was examined. Administration of PGE2, PGF2α, and PGI2 reduced basal (Na+ + K+)-ATPase activity by up to 30, 80, and 80%, respectively. PGE1 and PGD2 were ineffective at any concentration. Neither Mg2+-ATPase nor Ca2+-ATPase was affected by PG treatment. Kinetic analysis revealed that the (Na+ + K+)-ATPase activity reducing ability of PGE2, PGF2α and PGI2 was of a complex nature involving a reduction in Vmax and an elevation of the respective K values for either substrate or activator. These results demonstrate that some PG's are potent inhibitors of rat heart (Na+ + K+)-ATPase. These PG's produced varied inotropic influences on isolated heart preparations and it is uncertain whether their myocardial actions are dependent on enzyme inhibition.

Inotropic responsiveness of atrial myocardium bathed in Tris- or bicarbonate-buffered solutions

Atrial muscle of guinea pigs was used to study the inotropic influences of substituting a tris(hydroxymethyl)-aminomethane-buffered solution aerated with 100% O2 for a bicarbonate-buffered solution aerated with 95% O2-5% CO2 under otherwise equivalent in vitro conditions. Basal values of isometric contractile tension and its first derivative (dT/dt) were smaller and time to peak tension and time to 90% relaxation were longer in Tris- than in bicarbonate-bathed muscles. Both groups responded similarly to changes in stimulation frequently (0.1--2.2 Hz) and Ca2+ concentration (1.0--7.0 mM); however, maximal inotropic responses to these variables were smaller in the Tris-bathed atria. The negative inotropic effects of D600 and gentamicin were greater in the Tris group. Tris-bathed atria developed pulsus alternans when exposed to Mn2+ or a reduced Ca2+ concentration, whereas pulsus alternans did not occur in the bicarbonate group. A transient increase in contractility occurred in bicarbonate-bathed atria after treatment with 0.125 mM Mn2+, but only a negative response occurred in the Tris group. Thus important, and seemingly Ca2+-dependent, differences exist between the inotropic influences of Tris and bicarbonate solutions that may affect the utility of Tris-buffered (and/or bicarbonate deprived) heart muscle for studying certain inotropic interventions.