Mechanisms of platelet activating factor-induced changes in sheep tracheal blood flow.
1. The effects of platelet activating factor (PAF) have been studied on the cervical tracheal vasculature and smooth muscle of anaesthetized sheep. 2. The predominant action of PAF (2 pmol-2nmol) was a dose-dependent fall in tracheal vascular resistance. The maximum fall in resistance was -41.6% (-38.5 to -44.7%, 95% confidence interval) and the ED50 was 17 pmol (12-28 pmol). Lyso-PAF (200 pmol) did not change vascular resistance. 3. PAF had no effect on tracheal smooth muscle tone assessed by measuring changes in the external diameter of the trachea. 4. The fall in vascular resistance produced with PAF was unaffected by the anti-asthma drug nedocromil sodium (1 mg, i.a.), the cyclo-oxygenase inhibitor indomethacin (5 mg kg-1, i.v.), the leukotriene receptor antagonist FPL55712 (2 mg kg-1, i.v.), or a combination of the histamine H1- and H2-antagonists mepyramine (2 mg kg-1, i.v.) with cimetidine (5 mg kg-1, i.v.). The PAF antagonist WEB 2086 (300 micrograms kg-1, i.v.) significantly reduced the vasodilatation produced by PAF (before, -40.8 +/- 4.2%; after -16.5 +/- 5.9%, P less than 0.05). 5. Thus in this model, PAF is a potent vasodilator of the tracheal circulation but has no action on tracheal smooth muscle. The vasodilatation is mediated by specific PAF receptors and is not due to the release of prostanoids, leukotrienes or histamine.
Corfield
D R
DR
Department of Physiology, St George's Hospital Medical School, London.
Webber
S E
SE
Widdicombe
J G
JG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008688:Methacholine Compounds / Q000494:pharmacology; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D017835:Nedocromil; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011738:Pyrilamine / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014132:Trachea / Q000098:blood supply*; D014230:Triazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001381:Azepines; D002867:Chromones; D008688:Methacholine Compounds; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D015363:Quinolones; D014230:Triazoles; D017835:Nedocromil; C052518:WEB 2086; D002927:Cimetidine; C006312:FPL 55712; D011738:Pyrilamine; D007213:Indomethacin