Effect of arachidonic and eicosapentaenoic acids on acute lung injury induced by hypochlorous acid.
BACKGROUND
Hypochlorous acid (HOCl) is the main oxidant of activated polymorphonuclear neutrophil granulocytes (PMN) and generated by myeloperoxidase during respiratory burst. This study investigates the effects of HOCl on pulmonary artery pressure (PAP) and vascular permeability and characterises the influence of arachidonic acid (AA) and eicosapentaenoic acid (EPA) on the observed effects.


METHODS
HOCl (500, 1,000, 2,000 nmol/min) was continuously infused into the perfusate (Krebs-Henseleit buffer solution, KHB). AA or EPA in subthreshold doses (both 2 nmol/min) or buffer were simultaneously infused using a separate port. PAP, pulmonary venous pressure (PVP), ventilation pressure, and lung weight gain were continuously recorded. The capillary filtration coefficient (Kf,c) was calculated before and 30, 60, and 90 minutes after starting the HOCl infusion.


RESULTS
HOCl application resulted in a dose dependent increase in PAP and Kf,c. The onset of these changes was inversely related to the HOCl dose used. The combined infusion of AA with HOCl resulted in a significant additional rise in pressure and oedema formation which forced premature termination of all experiments. The combination of EPA with HOCl did not result in an enhancement of the HOCl induced rise in pressure and oedema formation.


CONCLUSIONS
Changes in the pulmonary microvasculature caused by HOCl are differently influenced by omega-6 and omega-3 polyunsaturated free fatty acids, suggesting a link between neutrophil derived oxidative stress and pulmonary eicosanoid metabolism.
Wahn
H
H
Medizinische Universitätsklinik Würzburg, Germany. h.wahn@medizin.uni-wuerzburg.de
Rüenauver
N
N
Hammerschmidt
S
S
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D003187:Compliance / Q000187:drug effects; D004537:Eicosanoic Acids / Q000494:pharmacology*; D005260:Female; D006997:Hypochlorous Acid / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D011669:Pulmonary Wedge Pressure / Q000187:drug effects*; D011817:Rabbits
D004537:Eicosanoic Acids; D016718:Arachidonic Acid; D006997:Hypochlorous Acid