Effects of endothelin receptor antagonists on bradykinin-induced increases in macromolecular efflux

William G. Mayhan, Israel Rubinstein

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The goal of this study was to determine the effects of endothelin receptor antagonists on agonist-induced increases in macromolecular extravasation in the hamster cheek pouch in vivo. We used intravital fluorescent microscopy and fluorescein isothiocyanate dextran (FITC-dextran; mol wt=70 K) to examine extravasation from postcapillary venules in response to bradykinin and endothelin before and following application of inhibitors of endothelin receptors (ETABand ETA). Increases in extravasation of macromolecules were quantitated by counting the number of venular leaky sites. Bradykinin (0.5 and 1.0 μM) and endothelin-1 (0.01 and 0.1 nM) produced a dose-related increase in the number of venular leaky sites and superfusion of PD 142893 (ETABantagonist), and PD 147953 and BQ-123 (ETAantagonists) significantly decreased bradykinin- and endothelin-induced responses. Addition of calcium to the superfusate restored bradykinin-induced increases in venular leaky sites in the presence of endothelin receptor antagonism. Thus, the findings of the present study suggest that endothelin receptor antagonists abrogate bradykinin- and endothelin-induced increases in macromolecular efflux from postcapillary venules. The mechanism for the effects of endothelin receptor antagonists appears to be related to inhibition of the ETAreceptor which, in turn, alters the mobilization of calcium across venular endothelium.

Original languageEnglish (US)
Pages (from-to)633-644
Number of pages12
JournalInflammation
Volume18
Issue number6
DOIs
StatePublished - Dec 1 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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