Thromboxane A2 inhibitors and iloprost prevent angiotensin II-induced oedema in the isolated perfused rat lung.
The effect of thromboxane A2 inhibitors and iloprost, a stable analogue of prostacyclin, on angiotensin II-induced oedema was studied in the isolated perfused rat lung. Angiotensin II, infused into the pulmonary artery, produced oedema of the lung, as evidenced by the increase in lung weight and in perfusion pressure. UK 38485, a thromboxane A2-synthetase inhibitor, and BM 13177, a thromboxane A2 receptor blocker, attenuated the oedema producing and vasoconstrictor effects of angiotensin II. A similar effect was obtained with iloprost at very low concentrations. Other agonists such as noradrenaline, phenylephrine and high K+ in the medium produced increases in perfusion pressure, but failed to elicit an increase in lung weight. Only serotonin, at relatively higher concentrations again increased lung weight, which was prevented by prior addition of UK 38485, BM 13177 and iloprost into the medium. These results were taken as an evidence indicating thromboxane A2 and prostacyclin-mediated effects of angiotensin II in the isolated perfused rat lung and the possible role of these unstable metabolites of arachidonic acid in the production of lung oedema.