PAF receptor blockade inhibits lung vascular changes in the rat monocrotaline model.
We recently reported that platelet-activating factor (PAF) levels increased in lung tissue after 1 subcutaneous injection of monocrotaline (MCT) (which causes lung injury), and, further, that treatment with PAF antagonists reduced pulmonary hypertension in this chronic lung injury rat model [15]. In the present study, we examined the effect of WEB 2170, a specific PAF antagonist, on MCT-induced pulmonary vascular remodeling. At 3 weeks after MCT injection, pulmonary hypertension in the animals was associated with an increase in the vessel wall thickness of the muscular arteries, reduction in number of peripheral arterioles, and right ventricular hypertrophy. In WEB 2170-treated rats, these changes were significantly less severe when compared with those observed in MCT-treated rats. In MCT-treated rats, there were significant increases in in vitro [3H]thymidine incorporation and accumulation of hydroxyproline in the lung tissue, and these changes were inhibited by WEB 2170 treatment. Our results suggest that PAF or a PAF-dependent sequence of events is involved in MCT-induced lung vascular remodeling.
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Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262.
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D000818:Animals; D001381:Azepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006909:Hydroxyproline / Q000032:analysis; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000517:prevention & control*; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010980:Platelet Membrane Glycoproteins; D011651:Pulmonary Artery / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects*; D043562:Receptors, G-Protein-Coupled; D013936:Thymidine / Q000378:metabolism; D014230:Triazoles / Q000627:therapeutic use*
D001381:Azepines; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; D016686:Monocrotaline; C063964:bepafant; D006909:Hydroxyproline; D013936:Thymidine