PROSTACYCLIN ANALOG (CICAPROST) PROTECTS AGAINST DAMAGE BY HYDROGEN-PEROXIDE TO RABBIT CARDIAC SARCOPLASMIC-RETICULUM

The membrane fluidity of the cardiac sarcoplasmic reticulum in rabbit was monitored by measuring changes in steady-state fluorescence anisot ropy (r(s)) using diphenylhexatriene as a probe. The Ca2+-ATPase activ ity of the sarcoplasmic reticulum was measured by assaying the amount of inorganic phosphate released from ATP. Hydrogen peroxide caused dam age to the sarcoplasmic reticulum, as reflected by decreases in membra ne fluidity and Ca2+-ATPase activity. The damage caused by hydrogen pe roxide was completely prevented by 20 mug/ml catalase. Cicaprost (240 nM) provided an effective protection against injury to the sarcoplasmi c reticulum caused by exposure to hydrogen peroxide. The r(s) value wa s significantly decreased from 0.154 +/- 0.014 to 0.122 +/- 0.005 (p < 0.01). Ca2+-ATPase activity was increased from 3.1 +/- 1.31 to 18.87 +/- 2.11 muM phosphate/mg protein/hour (p < 0.01). The protection give n by cicaprost was dose dependent. We conclude that cicaprost protects against damage produced by hydrogen peroxide in cardiac sarcoplasmic reticulum in the rabbit. The mechanism of the effect of cicaprost rema ins to be elucidated.