In vitro airway responsiveness of flinders sensitive and resistant line rats

Recently, we reported that freely moving Flinders sensitive line rats (FSL, selectively bred for their cholinergic hyperresponsiveness) are more susce ptible to allergen-induced airway hyperresponsiveness than their control co unterparts-Flinders resistant line (FRL) rats. In this study the two Flinde rs lines were compared for responsiveness of excised tracheal and primary b ronchial smooth muscle in vitro. FSL tissues were slightly but significantl y more sensitive to cholinergic stimulation than FRL tissues (slightly lowe r EC50 value for carbachol) but the FRL tissues were more responsive, exhib iting larger amplitude of response. Surprisingly, previous exposure to alle rgen challenge was accompanied by reduced in vitro responses to spasmogens in both rat lines. We conclude that FSL and FRL airways do not differ great ly with respect to sensitivity to cholinergic stimulation in vitro and that inflamed airways show reduced in vitro responses to spasmogens. The discre pancy between the in vivo and in vitro findings suggests that responsivenes s of airway smooth muscle involves regulation from both proximal and distal sites. (C) 2000 Academic Press.