The effect of in vivo hyperoxic exposure on the release of endogenous histamine from the rat isolated perfused lung.

Female rats were exposed to either 1 atm air or 100% O2 for 12, 24, or 48 hr. The rats were killed, the lungs were removed, and an isolated perfused lung (IPL) system was prepared. The isolated lung preparation was perfused with a modified Krebs-Henseleit buffer in a recirculating system, and the effect of the O2 exposures on histamine release from the IPL was determined. The effect of these O2 exposures on malondialdehyde formation in the IPL also was examined. Maximal release of histamine occurred after 20 min of perfusion. A linear relationship was found between the maximal histamine concentration released into the perfusate and the length of time the rats were exposed to normobaric hyperoxia. Malondialdehyde in lung perfusate also increased in a linear manner with increasing O2 exposure time. Addition of the H1-receptor antagonist, d-chlorpheniramine, to the perfusate completely inhibited basal histamine release from the IPL of both air- and O2-exposed rats, while addition of the H2-receptor antagonist, metamide, potentiated the release process. There was no significant effect demonstrated when an equimolar concentration of atropine was added to the perfusate. Arterial plasma histamine from rats exposed to 100% O2 for 24 hr increased 40% when compared to air-exposed controls, while histamine release from the IPL increased 75%. In conclusion, exposure of rats to normobaric hyperoxia caused both histamine release and malondialdehyde formation. Histamine release probably occurred as a result of a free radical-induced peroxidation of the lipid membrane of histamine-containing mast cells. Release of histamine from the IPL may be an early biochemical marker of damage by O2.