Relaxant effect of chemotactic peptides on rabbit vascular strips: evidence for nitric oxide release from a nonendothelial source.
Two distinct peptides, C5a and f-Met-Leu-Phe (FMLP), that are chemotactic for phagocytic leukocytes affect profoundly the circulation in various in vivo systems. These peptides are known to relax strips of rabbit isolated blood vessels, the portal vein and pulmonary artery. In the present study, the effect of recombinant human C5a (2.5-25 nM) was examined and found to be qualitatively similar to that previously reported for FMLP. Indomethacin completely or partially inhibited the vasorelaxations induced by either peptide in the pulmonary artery and the portal vein, respectively. The relaxation induced by C5a was not abolished by removing the endothelial lining of the model vessels. The C5a or FMLP effects were more tachyphylactic in tissues continuously exposed to cycloheximide; this phenomenon was particularly pronounced for FMLP. A series of experiments were focused on the indomethacin-resistant component of the relaxation induced by either peptide on the portal vein. This component was not inhibited by capsaicin pretreatment or by endothelium removal, but was suppressed by treatment with NG-nitro-L-arginine or reduced by LY-83583. These findings suggest that the chemotactic peptides elicit their mechanical effect on rabbit vascular smooth muscle through the release of secondary mediators not related to the endothelium; the mediators are tentatively identified as prostaglandins and nitric oxide. It is the coordinated combinations of the metabolic pathways that are involved in the final responses, with inherent differences between vessel sources and the agonists used.
Petitclerc
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Centre de recherche (Université Laval), Hôtel-Dieu de Québec, Canada.
Marceau
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F
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology*; D015936:Complement C5a / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D010455:Peptides / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects* / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits
D002630:Chemotactic Factors; D010455:Peptides; D019335:Nitroarginine; D009569:Nitric Oxide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D001120:Arginine; D003513:Cycloheximide