Leukocyte-induced endothelial dysfunction in the rabbit basilar artery: modulation by platelet-activating factor.
We studied the effects of polymorphonuclear leukocytes (PMNLs) activated by N-formyl-methionyl-leucyl-phenylalanine on the endothelium-dependent relaxation of the rabbit basilar artery (BA). In the presence of activated PMNLs the maximal vessel relaxation to acetylcholine (ACh) and bradykinin (endothelium-dependent dilators) was decreased from 62 +/- 7 and 48 +/- 6% to 23 +/- 9 and 19 +/- 7, respectively, (p < 0.05). The endothelium-independent relaxation to nitroprusside was not affected by PMNLs. When PMNLs were activated in the organ chamber in the presence of a low concentration of platelet-activating factor (PAF, 10(-10) mol/l), the depression of ACh- and bradykinin-induced relaxation increased by 27 +/- 9 and 23 +/- 7%, respectively (p < 0.05), though at this concentration PAF alone did not cause PMNLs to induce endothelial dysfunction. In addition, in the presence of PAF, activated PMNLs inhibited endothelium-dependent relaxation at lower cell concentrations and shorter periods of contact with the endothelium. PMNL effects on the endothelium were correlated with the level of cell exocytosis as tested by accumulation of beta-glucuronidase activity. In the presence of PAF, accumulation of this activity increased from 46 +/- 6 to 79 +/- 8 U/ml (p < 0.05). Examination of BA segments by scanning electron microscopy revealed that, after the treatment with activated PMNLs, the endothelium was morphologically preserved, but in the presence of PAF PMNLs caused more apparent microlesions in the endothelial layer. We conclude that small quantities of PAF potentiate the activation of marginated PMNLs. These cells then become more aggressive towards the endothelium, producing significant depression of the endothelium-dependent relaxation.
Akopov
S E
SE
Laboratoire de Recherches Cérébrovasculaires, CNRS UA 641, Université Paris VII, France.
Sercombe
R
R
Seylaz
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000378:metabolism* / Q000648:ultrastructure; D001920:Bradykinin / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D066298:In Vitro Techniques; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011817:Rabbits; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*
D010972:Platelet Activating Factor; D009599:Nitroprusside; D005966:Glucuronidase; D000109:Acetylcholine; D001920:Bradykinin