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14C-Arachidonic acid (AA, 66 nmol) was injected into the pulmonary circulation of isolated perfused hamster lungs. The metabolites were analysed from the nonrecirculating perfusion effluent, which was extracted with ethyl acetate first at pH 7.4 (to extract unmetabolized AA, metabolites of lipoxygenase and HHT) and then at pH 3.5 for prostaglandins and thromboxanes. When indomethacin was infused into the pulmonary circulation, the metabolism of AA was decreased dose dependently. The amounts of all metabolites were decreased rather similarly by indomethacin. The present study indicates that indomethacin inhibits arachidonate metabolism via cyclo-oxygenase and lipoxygenase in hamster isolated lungs.

14C-Arachidonate (50 nmol) was injected into the pulmonary circulation of isolated perfused lungs of female hamsters and the metabolites were analysed from the nonrecirculating perfusion effluent. Pulmonary infusion of dipyridamole (20 microM) increased the amount of radioactivity in the perfusion effluent of 0-4 min from 12.8 +/- 1.0% to 17.2 +/- 1.5% (2P less than 0.05) of the injected amount. Dipyridamole increased the amounts of PGF2 alpha, PGE2 and two unidentified metabolite groups in the effluent. An increasing trend was seen also in the amount of 6-keto-PGF1 alpha and TxB2. A decreasing trend was, however, seen in the amount of metabolites migrating near to unlabelled 15-keto-PGE2. When 20 nmol of 14C-PGE2 was injected into the pulmonary circulation of isolated hamster lungs, the amount of 15-keto-metabolites of PGE2 in the effluent was decreased and that of unmetabolized PGE2 increased by dipyridamole dose dependently. The rate of efflux of radioactivity from the lungs was increased by dipyridamole. Dipyridamole was in vitro not an inhibitor of 15-hydroxyprostaglandin dehydrogenase in the 100.000 supernatant fraction of homogenized hamster lungs. At 20 microM and 100 microM it even caused a slight in vitro activation of 15-hydroxyprostaglandin dehydrogenase. Thus the decreased pulmonary inactivation of PGE2 by dipyridamole is obviously due to the decreased uptake of PGE2 into the lungs. This could explain partly the detected changes in the pulmonary metabolism of arachidonic acid by dipyridamole.

The metabolism of prostaglandin E2 (PGE2) was decreased in isolated male hamster lungs, when sulfinpyrazone was infused into the pulmonary circulation. After pulmonary injection of 20 nmol of 14C-PGE2 the amount of 15-keto-metabolites of PGE2 was in the effluent from control lungs 4.0 +/- 0.5 nmol (mean +/- SEM) and in those from 20 mu M and 100 mu M sulfinpyrazone treated lungs 1.9 +/- 0.2 nmol (2P Less Than 0.01 compared to the control) and 1.7 +/- 0.4 nmol (2P Less Than 0.01), respectively. The amount of unmetabolized PGE2 was correspondingly increased in the effluent by sulfinpyrazone. The rate of efflux of the radioactivity from the lungs was increased by sulfinpyrazone. After injection of 10 nmol of 14C-PGE2 into the pulmonary circulation half of the injected radioactivity appeared in the effluent in 30 +/- 4 sec in control and in 15 +/- 0.7 sec (2P Less Than 0.01) in 20 mu M sulfinpyrazone experiments. Sulfinpyrazone had no effect on the activity of 15-hydroxyprostaglandin dehydrogenase in the 100.000 g supernatant fraction of homogenized hamster lungs. Thus the decreased metabolism of PGE2 in the pulmonary circulation of hamster lungs is obviously not due to the inhibition of 15-hydroxyprostaglandin dehydrogenase. A more likely explanation seems to be the decreased uptake of PGE2 into the lung cells.

Perfusion effluent from isolated rat and hamster lungs caused a relaxation of superfused strip of bovine coronary artery (BCA). This relaxation was abolished by pulmonary infusion of indomethacin. Pre-exposure of rats and hamsters to cigarette smoke during half an hour before the lung perfusion did not change the degree of this initial relaxation of BCA. Injection of 10 micrograms of sodium arachidonate (AA) into the pulmonary circulation of isolated hamster lungs caused a contraction of BCA, which was not changed by cigarette smoke pre-exposure. When AA (10 micrograms) was injected into the pulmonary circulation of isolated hamster lungs during cigarette smoke ventilation the contractions of superfused BCA and rat stomach strip (RSS) were not significantly different from those during the preceding and following air ventilation. In experiments with isolated rat lungs the initial relaxation of superfused BCA was accompanied by a contraction of superfused RSS. AA injection (10 micrograms) into rat lungs caused a further relaxation of BCA and contraction of RSS, which were abolished by pulmonary infusion of indomethacin. Cigarette smoke ventilation of isolated rat lungs caused a relaxation of superfused BCA, which was not abolished by indomethacin. During cigarette smoke ventilation injection of AA (10 micrograms) into the pulmonary circulation of rat lungs caused a relaxation of BCA and a contraction of RSS. The present study indicates that neither cigarette smoke ventilation nor pre-exposure to cigarette smoke has a drastic effect on the metabolism of arachidonic acid to myotropic compounds in isolated hamster and rat lungs.