Indomethacin suppresses the early cardiodepressant factor released by endotoxin in the rat: possible involvement of a prostacyclin-related material.
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.
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002478:Cells, Cultured; D003864:Depression, Chemical; D011464:Epoprostenol / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009201:Myocardial Depressant Factor / Q000096:biosynthesis*; D009543:Nifedipine / Q000494:pharmacology; D010452:Peptide Biosynthesis; D051381:Rats; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology*
D007093:Imidazoles; D009201:Myocardial Depressant Factor; D002110:Caffeine; C029899:imidazole; D011464:Epoprostenol; D009543:Nifedipine; D007213:Indomethacin