RUTHENIUM RED, BUT NOT CAPSAZEPINE REDUCES PLASMA EXTRAVASATION BY CIGARETTE-SMOKE IN RAT AIRWAYS

1 Cigarette smoke increases vascular permeability in rat airways by activating release of tachykinin from capsaicin-sensitive sensory nerves. However, the mechanism by which cigarette smoke induces secretion of sensory neuropeptides is unknown. Here we hypothesized that cigarette smoke activates sensory nerve endings via a mechanism similar to that of capsaicin. 2 We studied the effects of ruthenium red, an inorganic dye which blocks the cation influx promoted by capsaicin and of the capsaicin antagonist capsazepine on the increase in vascular permeability produced by cigarette smoke, capsaicin, hypertonic saline and substance P in the trachea of pentobarbitone anaesthetized rats. We also investigated the ability of cigarette smoke to desensitize sensory nerve fibres. 3 Ruthenium red (10 mm) by aerosol blocked the increase in vascular permeability induced by capsaicin (0.5 mum) and reduced the response to cigarette smoke (5 puffs) but did not affect responses evoked by hypertonic saline (7.2%) or by substance P (10 muM) (all given by aerosol). Aerosols of capsazepine (0.1 mm) prevented extravasation by capsaicin, but did not inhibit response to cigarette smoke, hypertonic saline or substance P. Finally, pre-exposure to a high dose of cigarette smoke (10 puffs) prevented the extravasation caused by cigarette smoke (5 puffs) itself and by intravenous capsaicin (150 mug kg-1), but not that by intravenous substance P (10 nmol kg-1). 4 The present results show that cigarette smoke: (a) increases vascular permeability in the rat airways by a mechanism that is not antagonized by capsazepine, and is partially sensitive to rutheniun red; (b) produces desensitization of capsaicin-sensitive sensory nerves. We propose that chemical(s) contained in or agent(s) produced by cigarette smoke in the airways share partially a common pathway with capsaicin to activate peptide release from capsaicin-sensitive sensory nerves, but do not bind to the putative 'capsaicin receptor'.