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-PGF1 alpha. 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-PGF1 alpha. 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.
Gillis
C N
CN
Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06510.
Havill
A M
AM
Moalli
R
R
D000527:Alprostadil / Q000378:metabolism*; D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced; D007022:Hypotension / Q000139:chemically induced; D007213:Indomethacin / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology*; D047069:Pyrazolones; D011817:Rabbits
D004731:Endotoxins; D011720:Pyrazoles; D047069:Pyrazolones; D000527:Alprostadil; C018845:nafazatrom; D007213:Indomethacin