Acute microcirculatory effects of platelet-activating factor.
Using the hamster cheek pouch preparation and intravital microscopy and fluorometry methods, we quantitated the dose-response effects of topically applied platelet-activating factor (PAF) on microvascular permeability, vessel diameter and leukocyte adhesion and investigated the biochemical pathways of this compound. Permeability alterations were assessed by the clearance of macromolecules. PAF increased macromolecular clearance in a dose-dependent manner with the maximum effect being obtained at 10(-7) M. Maximal vasoconstriction was induced by 10(-5) M PAF. Interestingly, PAF at 10(-9) M induced extensive adhesion of leukocytes to postcapillary endothelium, but did not produce changes in either vessel diameter or permeability. To elucidate the biochemical pathways of PAF activity, several inhibitors of the arachiodonic acid cascade and receptor blockers were employed. Dexamethasone and kadsurenone attenuated the clearance response to PAF, while indometacin, OKY-046 (a thromboxane A2 synthase inhibitor), and chlorpheniramine did not. Indometacin and OKY-046 prevented vessel diameter changes. Our results demonstrate that (1) PAF produces a dose-related extravasation of macromolecules, (2) leukotrienes may be responsible for the increased clearance of macromolecules caused by PAF, (3) PAF-induced vasoconstriction is mediated by thromboxane, (4) PAF stimulates leukocyte adhesion in an inverse dose relationship, and (5) responses to PAF are at least partially mediated by receptor interactions.
Durán
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WN
Department of Physiology, UMDNJ-New Jersey Medical School, Newark 07103-2757.
Dillon
P K
PK
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology* / Q000502:physiology; D013928:Thromboxane A2 / Q000096:biosynthesis; D014661:Vasoconstriction / Q000187:drug effects
D010972:Platelet Activating Factor; D013928:Thromboxane A2