We investigated direct histamine release and its effects in
edema formation following
paraquat (PQ) injury in a blood-free, perfused rat lung preparation. Under control conditions, perfusate
histamine levels from the lung averaged 9.5 +/- 1.4 ng/ml. Lungs perfused with
paraquat (1 mM) showed marked increases in pulmonary arterial pressure (133%), airway pressure (74%), alveolarcapillary
protein flux (200%), and lung weight (38%). Prior to any detectable lung weight or pressure changes, PQ caused
a 300% increase in perfusate
histamine.
Diphenhydramine (1.0 X 10(-5) M), a specific H1-histamine receptor antagonist, blocked the increased
protein flux that followed PQ administration and significantly delayed
edema. Furthermore,
diphenhydramine attenuated the rise in
PGF2 alpha. Conversely, histamine release was partially attenuated by the
cyclooxygenase inhibitor,
ibuprofen, at 2.4 X 10(-5) M, the same level that we had previously shown to block an early rise in
PGF2 alpha and the onset of
edema after PQ. These data show that the increased alveolar-capillary
protein flux that occurred with PQ injury was attenuated by an H1-receptor antagonist and suggest that
histamine is a primary mediator in
paraquat-induced injury and that
histamine subsequently stimulates
prostaglandin release.