CV6209 inhibits airway wall thickening and airway hyperresponsiveness to histamine induced by intravenous administration of platelet-activating factor in guinea pigs.
We studied the effect of intravenous administration of platelet-activating factor (PAF) on airway responsiveness to histamine and airway wall thickening in guinea pigs. Guinea pigs were killed and the lungs were fixed in formalin. Slides from paraffin-embedded sections of the lungs were stained and the airways that were cut in transverse section were measured by tracing enlarged images using a digitizer. Moreover, airway resistance (Raw) was determined by a pulmonary mechanics analyzer and we calculated two indices, an index of airway wall thickening and one of airway hyperresponsiveness to histamine, from changes of baseline-Raw and peak-Raw following intravenous administration of histamine before and after PAF administration. The infusion of 600 ng/kg PAF for 1 h induced an increase in the thickness of the airway wall in main bronchi demonstrable by histological examination. In analysis of airway function, the infusion of 600 ng/kg PAF for 1 h induced airway hyperresponsiveness to histamine with airway wall thickening. The PAF antagonist CV6209, which was given intravenously 30 min prior to PAF administration, inhibited these effects of PAF in a dose-dependent manner, suggesting PAF may induce airway wall thickening and airway hyperresponsiveness through PAF receptors in the airways.
Kurosawa
M
M
Department of Dermatology, Gunma University School of Medicine, Maebashi, Japan.
Tsukagoshi
H
H
Igarashi
Y
Y
Miyachi
Y
Y
D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001249:Asthma / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D008168:Lung / Q000187:drug effects*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*
D006633:Histamine Antagonists; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209; D006632:Histamine