Evidence against a role for platelet-activating factor in hypoxic pulmonary vasoconstriction in the rat.
1. The effect of two structurally different platelet-activating factor (PAF) receptor antagonists, WEB 2086((3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-[1,2,4]- treazolo-[4,3-alpha][1,4]-diazepine-2-yl]-1-(morpholinyl)-1- propanone)) and BN 52021, on hypoxic pulmonary vasoconstriction (HPV) was studied using an isolated rat lung preparation perfused with blood. 2. In lungs treated with WEB 2086 there was a dose-dependent attenuation of HPV, with complete abolition of HPV at the maximum dose. 3. Low doses of WEB 2086 caused only slight diminution of the pressor response to angiotensin II, although higher doses caused increasing attenuation of the angiotensin pressor response. 4. BN 52021 did not affect HPV. 5. Injection of PAF caused an increase in pulmonary artery pressure of 145%, a response abolished by pretreatment of the lungs with either WEB 2086 or BN 52021. 6. These results suggest that PAF does not mediate HPV in the rat.
McCormack
D G
DG
Cardiothoracic Institute, London.
Barnes
P J
PJ
Evans
T W
TW
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004224:Diterpenes; D046934:Ginkgolides; D000860:Hypoxia / Q000503:physiopathology*; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles; D014661:Vasoconstriction
D001381:Azepines; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D014227:Triazines; D014230:Triazoles; C052518:WEB 2086; C045856:ginkgolide B