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Exocytosis of Endothelin‐1 from Endothelial Weibel‐Palade Bodies Contributes to Vasoconstriction in Aged Arteries
Author(s) -
Goel Aditya A,
Lowenstein Charles,
Berkowitz Dan,
Flavahan Nicholas
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.965.12
Subject(s) - exocytosis , thrombin , vasoconstriction , medicine , contraction (grammar) , von willebrand factor , endothelium , endothelin receptor , endocrinology , chemistry , endothelin 1 , microbiology and biotechnology , biology , receptor , secretion , platelet
Endothelin‐1 (ET) has been localized to Weibel‐Palade Bodies (WPB) in endothelial cells. Experiments were performed to analyze the role of WPB‐derived ET in arterial regulation. Aortas from young (3 months) and aged F344 rats (19 months) were isolated and processed for isometric tension recording, ET release and immunofluorescent analysis. After inhibition of NO synthase (L‐NAME, 100 µM), thrombin (1U/ml) caused rapid contraction of aged aortas that was abolished by endothelial‐denudation, the ETA receptor antagonist BQ123 (1 µM) or by TAT‐NSF (1 µM), a cell‐permeable inhibitor of N‐ethylmaleimide sensitive factor (NSF) and inhibitor of WPB exocytosis. In young aortas, thrombin (1 U/ml) evoked a small contraction that was not inhibited by BQ123 or endothelial denudation. The response to thrombin in aged aortas was associated with a 5‐fold increase in ET release that was prevented by TAT‐NSF or endothelial‐denudation. WPBs were visualized by immunofluorescent imaging of von Willebrand factor using laser scanning microscopy of aortic segments. In aged aortas, thrombin caused a marked translocation of WPB to the cell surface. In conclusion, the acute release and exocytosis of ET from endothelial cells can contribute to vascular regulation. The dramatic increase in this activity in aged arteries might contribute to thrombogenic and inflammatory events associated with aging. (NIH grants # HL 80119 and OH 8531)