IN-VIVO EXPOSURE TO NITROGEN-DIOXIDE (NO2) INDUCES A DECREASE IN CALCITONIN-GENE-RELATED PEPTIDE (CGRP) AND TACHYKININ IMMUNOREACTIVITY IN GUINEA-PIG PERIPHERAL AIRWAYS

The mammalian respiratory tract is densely innervated by sensory and a utonomic fibres, Subsets of the nerves contain bioactive regulatory pe ptides, such as substance P, calcitonin gene-related peptide (CGRP), a nd neurokinins. The sensory nervous system responds to inhaled irritan ts, resulting in a release of neuropeptides and, thus, a decrease in t he peptide immunoreactivity of the fibres. We examined the effects of inhaled nitrogen dioxide (NO2), a well-known indoor and outdoor air po llutant, on pulmonary sensory neuropeptides. Guinea-pigs were exposed for 4 h to 18 parts per million (ppm) NO2 or to air (n=5 each), At the end of the exposure, they were killed with urethane and their lungs w ere fixed in 1% paraformaldehyde in phosphate-buffered saline, Cryosta t sections were stained with antisera to an anatomical nerve marker, p rotein gene product (PGP) 9.5, and to CGRP and tachykinins, utilizing the avidin-biotinylated peroxidase method. In the noncartilaginous air ways (diameter <250 mu m) of NO2-exposed animals, less tachykinin- and CGRP-immunoreactive nerve fibres were found compared with controls, N o change was seen in the total nerve fibre distribution (PGP 9.5). It is concluded that the peptidergic nerves of guinea-pig peripheral airw ays are a sensitive indicator of exposure to nitrogen dioxide.