Airway function after cyclooxygenase inhibition during hyperpnea-induced bronchoconstriction in guinea pigs

Airway function deteriorates significantly on cessation of exercise or isoc apnic hyperventilation challenges but is largely preserved during the chall enge in humans and guinea pigs. PGE(2), an endogenous bronchodilator, might be responsible for the preservation of lung function during hyperventilati on (HV). We hypothesized that PGE(2) might have a protective effect during HV, partially explaining the minimal changes in respiratory system resistan ce (Rrs) usually seen during HV in humans and guinea pigs. Therefore, chang es in Rrs were measured during and after HV in anesthetized, mechanically v entilated guinea pigs treated with flurbiprofen (FBN) or placebo. With HV, there was an initial bronchodilation that was unaffected by FBN. Rrs then i ncreased with time during HV, an effect that was blocked by FBN. After HV, Rrs increased further in all groups, but the increase in Rrs was less in th e FBN-treated groups. FBN treatment reduced the PGE(2) concentration slight ly in lung lavage fluid compared with placebo. We found no enhancement or r efractoriness of the Rrs response to repeat bouts of HV and no effect of FB N treatment on the response of Rrs to repeat HV. These results suggest that a constrictor PG is released during and possibly after HV and that the pos t-HV increase in Rrs is the sum of effects of the PG released during HV and a second constrictor mechanism operating after HV. We found no evidence fo r bronchodilator PG during or after HV in the guinea pig.