Platelet activating factor causes hyperconstriction at the inflammatory coronary lesions in pigs in vivo
| Autor: | Naoki Katsumata, Hiroaki Shimokawa, Kouichi Kuwata, Toshiaki Kadokami, Tohru Yamawaki, Akira Takeshita, Kensuke Egashira, Toshiyuki Kozai, Yoshihiro Fukumoto |
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| Rok vydání: | 1997 |
| Předmět: |
Male
Pathology medicine.medical_specialty Serotonin medicine.drug_class Swine Coronary Vasospasm Inflammation Pyridinium Compounds Pharmacology Dinoprost chemistry.chemical_compound In vivo Tetrahydroisoquinolines medicine Animals Platelet Platelet Activating Factor Protein kinase C Protein Kinase C Platelet-activating factor business.industry Drug Synergism General Medicine Receptor antagonist Isoquinolines Coronary Vessels chemistry Vasoconstriction lipids (amino acids peptides and proteins) medicine.symptom Cardiology and Cardiovascular Medicine business Histamine Platelet Aggregation Inhibitors Interleukin-1 |
| Zdroj: | Coronary artery disease. 8(7) |
| ISSN: | 0954-6928 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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