Indomethacin suppresses the early cardiodepressant factor released by endotoxin in the rat: possible involvement of a prostacyclin-related material.

Abstract

Unlabelled: The aim of this study was to determine if a prostaglandin-related material--in particular prostacyclinlike substance--could explain our previous findings showing that a sublethal dose of endotoxin caused the early release of a serum lipid-soluble factor able to decrease various activities of cultured rat heart cells (CRHC) through an intracellular calcium dysregulation. Sera were sampled from rats 4 h after administration of 2 mg/kg E coli endotoxin (E) and their cardiodepressant effect on CRHC determined by an electrooptical technique. E-treated rat serum (ETRS) cardiodepressant effect was compared to that of 0.1 ng/ml prostacyclin (PGI2) and of 0.029 ng/ml nifedipine, a calcium antagonist. The reversal effect of caffeine, a substance known for its positive inotropic effect by increasing intracellular calcium availability at the sarcoplasmic reticulum site, has been tested against the depressant effect of ETRS, PGI2, and nifedipine.

Results: 1) Compared to control, serum from endotoxin-treated rats with or without imidazole pretreatment depressed contractility of CRHC in a similar fashion, whereas pretreatment with indomethacin had a much less marked effect; 2) PGI2, nifedipine, and ETRS depressed CRHC contractility in much the same way; 3) caffeine reversed the depressant effect of PGI2 and ETRS, but was much less effective against nifedipine effect. These results suggest that the cardiodepressant effect of ETRS is mediated by a prostaglandinlike substance, other than thromboxane, acting through reduced intracellular calcium availability. PGI2 or PGI2-related material is consistent with such a depressant effect and such a mechanism.