[Lung 3H-thymidine incorporation in monocrotaline (MCT)-treated rats--role of platelet-activating factor (PAF)].
Monocrotaline (MCT) causes chronic pulmonary hypertension associated with pulmonary vascular thickening in rats. Since components of the pulmonary vascular thickening are reflected in increased DNA synthesis in medial smooth muscle cells, and since platelet-activating factor (PAF) has been reported to contribute to the pulmonary hypertension induced by MCT, we examined the effect of WEB 2170, a specific PAF receptor blocker, on MCT-induced pulmonary vascular thickening and in vitro 3H-thymidine incorporation into lung tissue, as an index of stimulation of cell proliferation. In MCT-treated rats, pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular thickening developed at 3 weeks after injection. Also, in MCT-treated rat lung tissue, there was a significant increase in the in vitro 3H-thymidine incorporation rate. In WEB 2170-treated MCT rats, these changes were significantly less severe than those observed in rats receiving MCT alone. We conclude that PAF plays a role in the inflammatory process that contributes to the development of pulmonary hypertension and vascular remodeling associated with increased lung cell proliferation in MCT-treated rats.
Ono
S
S
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Tanita
T
T
Ashino
Y
Y
Noda
M
M
Tabata
S
S
Hoshikawa
Y
Y
Ueda
S
S
Nishimura
T
T
Fujimura
S
S
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D016686:Monocrotaline; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000493:pharmacokinetics*; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; D016686:Monocrotaline; D004247:DNA; C063964:bepafant; D013936:Thymidine