Because
leukotrienes and
prostaglandins are inflammatory mediators derived from
arachidonic acid, their potential role in
oleic acid-induced
lung injury was evaluated in control and in essential
fatty acid-deficient (EFAD) rats depleted of
arachidonic acid substrate. In control rats,
oleic acid (0.06 ml/kg iv) increased the pulmonary permeability index (measured by scintigraphy) from -10 +/- 13 x 10(-6) s-1 to 217 +/- 20 x 10(-6) s-1 and 118 +/- 13 x 10(-6) s-1 at 5 and 50 min (P less than 0.05), respectively. It also caused arterial
hypoxemia at 30 min (P less than 0.05). Compared with saline controls,
oleic acid increased bronchoalveolar lavage fluid levels of immunoreactive (i)
LTC4/D4, iLTB4, (P less than 0.01), and
6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) (P less than 0.05). In EFAD rats,
oleic acid failed to significantly increase the lung permeability index at 5 and 50 min. In contrast to control rats,
oleic acid failed to cause
hypoxemia in the EFAD rats. Bronchoalveolar lavage levels of iLTB4 and i6-keto-PGF1 alpha after
oleic acid in EFAD rats were lower compared with
oleic acid controls, whereas iLTC4/D4 in the
oleic acid EFAD group was not decreased. Treatment with intraperitoneal
ethyl arachidonate (400 mg over 2 wk) reversed the resistance of EFAD rats such that the
pulmonary edema (P less than 0.05) was evident after
oleic acid. This latter group also manifested a significant (P less than 0.05) rise in the bronchoalveolar lavage levels of iLTB4 and i6-keto-PGF1 alpha. These results suggest that
arachidonic acid metabolites contribute to
oleic acid-induced pulmonary permeability.