title: Platelet activating factor causes hyperconstriction at the inflammatory coronary lesions in pigs in vivo.
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-1 beta (IL-1 beta) in vivo.
  
  
  METHODS
  Under aseptic conditions, the proximal segment of the porcine left coronary artery was dissected and wrapped with cotton mesh absorbing IL-1 beta. Two weeks after the operation, coronary vasomotion in response to intracoronary administration of 0.3 and 1 microgram/kg PAF, 1, 3, and 10 micrograms/kg serotonin, 1, 3 and 10 micrograms/kg histamine, and 5 and 50 micrograms/kg prostaglandin F2 alpha was examined by coronary arteriography.
  
  
  RESULTS
  At the IL-1 beta-treated site, PAF, serotonin and histamine, but not prostaglandin F2 alpha, 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.
authors.affiliation: Research Institute of Angiocardiology, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kozai
authors.forename: H
authors.initials: H
authors.lastname: Shimokawa
authors.forename: T
authors.initials: T
authors.lastname: Yamawaki
authors.forename: Y
authors.initials: Y
authors.lastname: Fukumoto
authors.forename: T
authors.initials: T
authors.lastname: Kadokami
authors.forename: K
authors.initials: K
authors.lastname: Kuwata
authors.forename: N
authors.initials: N
authors.lastname: Katsumata
authors.forename: K
authors.initials: K
authors.lastname: Egashira
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000818:Animals; D003329:Coronary Vasospasm / Q000209:etiology* / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D015237:Dinoprost / Q000494:pharmacology; D004357:Drug Synergism; D006632:Histamine / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011726:Pyridinium Compounds / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D044005:Tetrahydroisoquinolines; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D007375:Interleukin-1; D007546:Isoquinolines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011726:Pyridinium Compounds; D044005:Tetrahydroisoquinolines; D012701:Serotonin; D006632:Histamine; D015237:Dinoprost; D011493:Protein Kinase C; C067430:TCV 309