Actions of platelet-activating factor on isolated rabbit basilar artery: modulation by activated polymorphonuclear leukocytes.
In segments of rabbit basilar artery (BA) platelet-activating factor (PAF) initiated a concentration-dependent transitory contraction which was unaffected by indomethacin or nordihydroguaiaretic acid (NDGA). N omega-nitro-L-arginine (NLA) did not change the magnitude of PAF-induced contraction, but in the presence of NLA the contraction tended to be more prolonged. In precontracted BA segments, PAF caused a concentration-dependent relaxation which was unaffected by NDGA. Indomethacin and NLA decreased PAF-induced relaxation by 10-30 and 70-90%, respectively; in combination these agents totally eliminated PAF-induced vessel reactions. Treatment of BA segments by rabbit peritoneal polymorphonuclear leukocytes (PMNLs) activated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) for 20 min led to PMNL adhesion to the vascular endothelium and a significant decrease (60-100%) in acetylcholine-induced endothelium-dependent vessel relaxation. After the treatment of BA segments, PAF induced strong, slow, tonic contraction of either non-precontracted or precontracted vessels which was unaffected by indomethacin or NLA. NDGA decreased this contraction by 30-60%. These results indicate that PAF is an endothelium-dependent vasodilator that can also produce an insignificant constrictor effect. However, when the vessels are affected by activated PMNLs, PAF is transformed to a strong vasoconstrictor, presumably due to the generation of as yet unknown vasoconstrictor stimuli resulting from PMNL-endothelium interactions. Under these conditions the PAF-induced contraction is partly mediated by 5-lipoxygenase metabolites.
Akopov
S E
SE
Laboratoire de Recherches, Cérébrovasculaires, CNRS UA 641, Université Paris VII, France.
Sercombe
R
R
Seylaz
J
J
D000818:Animals; D001488:Basilar Artery / Q000502:physiology*; D002448:Cell Adhesion; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects
D010972:Platelet Activating Factor; D009637:Masoprocol; D007213:Indomethacin