[Effects of oxygen free radicals on the function of the cardiac sarcoplasmic reticulum]

Peroxidative stress, exerted by oxygen free radicals, seems to be an important mechanism of the ischemia-reperfusion myocardial damage. In the present study we evaluated the modifications of sarcoplasmic reticulum function subjected to peroxidation by ferric ions. A subcellular fraction enriched in sarcoplasmic reticulum was obtained from rabbit hearts by homogenization and differential centrifugations. Sarcoplasmic reticulum vesicles were peroxidated through incubation for 5 min at 37 degrees C in presence of ferric cloride (FeCl3) ranging in concentration between 0.3 and 0.9 mM. Peroxidation of sarcoplasmic reticulum vesicles determined a dose-dependent reduction of Ca-uptake (39.2 +/- 10.3, 36.5 +/- 9.9, 28.9 +/- 8.4 and 18.8 +/- 8.2 nmol/min/mg in presence of 0, 0.3, 0.6 e 0.9 mM FeCl3; NS, p less than 0.05 and less than 0.01, respectively) which was paralleled by an increase in the production of malondialdehyde, an index of lipid peroxidation (1.0 +/- 1.0, 7.0 +/- 3.2, 14.1 +/- 3.9 and 27.0 +/- 4.7 nmol/mg in presence of 0, 0.3, 0.6 e 0.9 mM FeCl3; p less than 0.05, less than 0.01 and less than 0.01, respectively). Depression of Ca-uptake was not accounted for by modifications of Ca-ATPase activity or membrane aspecific permeability to Ca++ ions, since these parameters were not affected by exposure to 0.3-0.9 mM FeCl3. On the contrary, the responsiveness of Ca-release channels to the specific inhibitor ryanodine was greatly altered, even at lower FeCl3 concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)