||ManTech Environmental Technology, Inc., Research Triangle Park, NC. ;Utah Univ., Salt Lake City. ;McGuire Clinic, Richmond, VA.;Health Effects Research Lab., Research Triangle Park, NC.
Airway hyperreactivity (AHR) to intravenous acetylcholine has been demonstrated 3d after F-344 rats were intranasally instilled with a rat-adapted influenza virus (ARRD, A657:1990). N-acetyl cysteine (NAC), an oxidant scavenger, was able to block AHR if orally administered (1% in tap water) for 2d prior to virus infection and continued for 3d until AHR was examined. To evaluate if these oxygen radicals derived from altered adenosine metabolism were responsible for AHR, oxypurinol (OXY) was administered (50 mg/kg, i.p.) for 4d prior to virus infection and AHR challenge. Virus increased xanthine oxidase (XO) activity and OXY inhibited this effect, but AHR was not blocked. However, virus-infected OXY-pretreated animals had less protein in the bronchoalveolar lavage suggesting that OXY had reduced a portion of the virus-induced lung damage. Experiments are currently in progress to see if oxidative damage from leukocytes, rather than altered adenosine metabolism, contribute to AHR.