Effect of nafazatrom and indomethacin on pulmonary removal of prostaglandin E1 after endotoxin in rabbits

1 We compared the effects of endotoxin on pulmonary prostaglandin E1 (PGE1) removal in groups of rabbits pretreated with the cyclo‐oxygenase inhibitor, indomethacin, or nafazatrom (Bay g 6575), which has been shown to increase plasma prostacyclin concentrations. 2 In untreated animals, endotoxin transiently decreased pulmonary removal of [3H]‐PGE1, caused pulmonary hypertension, systemic hypotension and increased plasma concentrations of PGE2 and 6‐keto‐PGF1α. 3 Indomethacin pretreatment prevented the transient decrease in pulmonary removal of [3H]‐PGE1 in response to endotoxin, prevented the haemodynamic effects and inhibited prostaglandin synthesis. Pretreatment with nafazatrom did not affect the decreased pulmonary removal of [3H]‐PGE1, exacerbated the haemodynamic response, reduced survival and potentiated the increase in circulating 6‐keto‐PGF1α. 4 We conclude that indomethacin acts to prevent the depression of pulmonary [3H]‐PGE1 removal by eliminating surface area changes associated with endotoxin‐induced pulmonary vasoconstriction. 5 These data suggest that nafazatrom treatment results in exacerbation of the endotoxin‐induced systemic hypotension presumably due to its effect on increased plasma prostacyclin during the later phase of endotoxaemia.