Platelet activating factor causes hyperconstriction at the inflammatory coronary lesions in pigs in vivo

Toshiyuki Kozai, Hiroaki Shimokawa, Tohru Yamawaki, Yoshihiro Fukumoto, Toshiaki Kadokami, Kouichi Kuwata, Naoki Katsumata, Kensuke Egashira, Akira Takeshita

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background. Although platelet activating factor (PAF) is an important vasoactive substance released from activated leukocytes, platelets and endothelial cells, little is known about its effect at the inflammatory coronary lesions in vivo. Objective. To examine the coronary vasomotor responses to PAF at the inflammatory lesions in our swine model with interleukin-1β (IL-1β) in vivo. Methods. Under aseptic conditions, the proximal segment of the porcine left coronary artery was dissected and wrapped with cotton mesh absorbing IL-1β. Two weeks after the operation, coronary vasomotion in response to intracoronary administration of 0.3 and 1 μg/kg PAF, 1, 3, and 10 μg/kg serotonin, 1, 3 and 10 μg/kg histamine, and 5 and 50 μg/kg prostaglandin F(2α) was examined by coronary arteriography. Results. At the IL-1β-treated site, PAF, serotonin and histamine, but not prostaglandin F(2α), caused hyperconstriction (n = 8). A synergy of the vasoconstricting effects of PAF and serotonin was also noted (n = 6). Administration of TCV-309, a selective PAF receptor antagonist, abolished the hyperconstrictive responses to PAF but not those to other agonists (n = 6). The PAF-induced coronary hyperconstrictions were significantly inhibited by administrations of the protein kinase C inhibitors staurosporine and sphingosine, but not by administrations of ryanodine, thapsigargin, or indomethacin (n = 4 each). Conclusions. These results indicate that PAF causes hyperconstriction at the inflammatory coronary lesions in vivo by itself as well as in a synergistic manner with serotonin and that the PAF-induced hyperconstrictions are substantially mediated by a protein kinase C dependent pathway in vivo.

Original languageEnglish
Pages (from-to)423-432
Number of pages10
JournalCoronary Artery Disease
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 1997

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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