Defibrotide, by enhancing prostacyclin generation, prevents endothelin-1 induced contraction in human saphenous veins

F. Berti, G. Rossoni, G. Biasis, A. Buschi, V. Mandelli, C. Tondo

Research output: Contribution to journalArticle

Abstract

Spirals of human saphenous veins (HSV), mounted in a 5 ml organ bath containing Krebs-Henseleit solution (37°C), when kept in contact with defibrotide (100-200 ug/ml) for 15 min, enhance (2 and 3 fold) their own basal release of 6-keto-PGF (61 ± 1.3 pg/mg w.t. n = 12). The phenomenon was long lasting upon repeated washing and sensitive to indomethacin (1 ug/ml). Endothelin-1 (ET-1, 20-40 ng) induced a sustained contraction of HSV and concomitantly released from the venous tissue a proportional amount of 6-keto-PGF. Indomethacin (1 ug/ml), by inhibiting cyclo-oxygenase enzyme, potentiated the contractile activity of ET-1 in HSV whereas exogenous PGE2 (20 ng/ml) considerably reduced the tension developed by the peptide on this venous tissue. Defibrotide (200 ug/ml), by releasing 6-keto-PGF, and other vasoactive prostaglandins, antagonized the contractile effect ET-1 (20 ng) in HSV. This data indicates that the eicosanoid metabolism is involved in the modulation of the potent vasoconstrictor effect of ET-1 in HSV and that PGI2-releaser, such as defibrptide, may have therapeutical value against immoderate changes of venous tone.

Original languageEnglish
Pages (from-to)337-350
Number of pages14
JournalProstaglandins
Volume40
Issue number4
DOIs
Publication statusPublished - 1990

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

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