Interleukin-1 beta potentiates endothelin ETB receptor-mediated contraction in cultured segments of human temporal artery

Segments of human temporal artery were placed in organ culture for up to 4 days and examined for endothelin ETB receptor activity in the presence and absence of the pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) by in vitro pharmacology and reverse transcriptase polymerase chain reaction ( RT-PCR). The contractile effect of prostaglandin F-2 alpha (used as a refer ence), was not significantly altered by culture or IL-1 beta. However, the selective ETB agonist sarafotoxin S6c induced no contraction in fresh arter ies, but marked contraction after culture. Both maximal contraction and pot ency to sarafotoxin S6c were increased in segments incubated with IL-1 beta . The contraction was sensitive to BQ 788 (ETB antagonist), but not FR 1393 17 (ETA antagonist). Actinomycin D abolished the contraction, whereas only the cytokine-induced increase in contraction was inhibited by cycloheximide . ETA and ETB receptor mRNAs were detected in all arteries; predominantly f or the ETA receptor in fresh arteries, and for the ETB receptor after cultu re. However, there was no change in the ETA/ETB receptor mRNA ratio after t reatment with IL-1 beta. This suggests de novo synthesis of contractile ETB receptors after organ culture and that IL-1 beta may further stimulate tra nslation of the mRNA to active receptors. The results raise the possibility that contractile ETB receptors may be implicated in disease states with in flammatory processes. (C) 1999 Elsevier Science B.V. All rights reserved.