Inhibition of cyclooxygenase production does not prevent arachidonate from increasing extravascular lung water and albumin in an isolated dog lung.
We examined the hypothesis that arachidonic acid can lead to pulmonary edema, increased pulmonary vascular permeability, and increased pulmonary vascular resistance (PVR) in an isolated dog lung. The lung was perfused with a dextran-salt solution to remove blood elements. Compared to controls, 20 mg/min sodium arachidonate into the pulmonary circulation led to edema and to an increase in a permeability and surface area index (PSI%), PVR, and cyclooxygenase (i.e. prostaglandin) production as measured by 6-keto-PGF1 alpha, TXB2 and PGF2 alpha. With 20 mg/min arachidonate, indomethacin inhibited the increase in cyclooxygenase production, reduced the increase in PVR and increased the edema and PSI%. Indomethacin, alone, did not produce edema or an increase in PSI% or PVR. Lower doses of arachidonate (0.1 to 5 mg/min) led to increasing cyclooxygenase production without obvious edema or an increase in PSI% or PVR. We conclude: 1) arachidonate can lead to pulmonary edema and an increase in PVR, and may lead to an increase in pulmonary vascular permeability; these effects of arachidonate do not require normal numbers of circulating blood elements; 2) arachidonate appears to contribute to pulmonary edema and increased PSI% by a noncyclooxygenase effect since inhibition of cyclooxygenase production did not prevent, and lower doses of cyclooxygenase production did not produce edema or an increase in PSI%; 3) the increase in PVR appeared to have a cyclooxygenase component since inhibition of cyclooxygenase production reduced the increase, and 4) indomethacin can increase the magnitude of edema and PSI% from arachidonate by an undefined mechanism.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D015237:Dinoprost; D004285:Dogs; D005110:Extracellular Space / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects*; D011460:Prostaglandins F / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced*; D012709:Serum Albumin / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects
D001095:Arachidonic Acids; D011460:Prostaglandins F; D012709:Serum Albumin; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015237:Dinoprost; D007213:Indomethacin