title: Pulmonary hypertension and edema induced by platelet-activating factor in isolated, perfused rat lungs are blocked by BN52021.
abstract: The experimental intravenous administration of platelet activating factor (PAF) induces pulmonary hypertension and directly or indirectly increases capillary permeability. Selective PAF antagonists BN52021 and L652-731 have been shown to inhibit the action of PAF in vitro and in vivo. Using a unique isolated perfused rat lung model, we measured the effect of these PAF antagonists on PAF-induced pulmonary hypertension and edema. Isolated rat lungs were perfused with Krebs-Henseleit solution. The right and left pulmonary arteries were dissected so that they could be perfused selectively, permitting the use of one lung as an internal control for a specific pharmacologic challenge. Exposure of one lung to PAF induced an increase of perfusion pressure and wet/dry lung weight ratio in a dose-dependent manner compared with the control lung. The PAF antagonists attenuated the increase in perfusion pressure and wet/dry lung weight caused by PAF (0.75 micrograms) in a dose-dependent manner. In addition, prostaglandin F2 alpha induced an equivalent increase in pulmonary pressure without causing a similar increase in lung edema. PAF-induced pulmonary hypertension and the increase in wet/dry lung weight ratio appear to be PAF receptor-mediated processes, and the use of specific antagonists and this technique may be useful probes to determine the role of PAF in pathophysiologic states.
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis.
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.forename: G M
authors.initials: GM
authors.lastname: Vercellotti
authors.forename: C F
authors.initials: CF
authors.lastname: Moldow
authors.forename: H S
authors.initials: HS
authors.lastname: Jacob
authors.forename: E K
authors.initials: EK
authors.lastname: Weir
mesh_terms: D000818:Animals; D004224:Diterpenes; D004487:Edema / Q000139:chemically induced* / Q000517:prevention & control; D005663:Furans / Q000494:pharmacology; D046934:Ginkgolides; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000517:prevention & control; D007269:Injections, Intra-Arterial; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects*; D008297:Male; D009929:Organ Size; D010477:Perfusion; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004224:Diterpenes; D005663:Furans; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran; C045856:ginkgolide B