Premium
Effect of nafazatrom and indomethacin on pulmonary removal of prostaglandin E 1 after endotoxin in rabbits
Author(s) -
Gillis C. Norman,
Havill Andrew M.,
Moalli Richard
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb11269.x
Subject(s) - prostacyclin , hypoxic pulmonary vasoconstriction , pulmonary hypertension , hemodynamics , medicine , prostaglandin , vasoconstriction , endocrinology , pharmacology , iloprost , chemistry
1 We compared the effects of endotoxin on pulmonary prostaglandin E 1 (PGE 1 ) 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 [ 3 H]‐PGE 1 , caused pulmonary hypertension, systemic hypotension and increased plasma concentrations of PGE 2 and 6‐keto‐PGF 1α . 3 Indomethacin pretreatment prevented the transient decrease in pulmonary removal of [ 3 H]‐PGE 1 in response to endotoxin, prevented the haemodynamic effects and inhibited prostaglandin synthesis. Pretreatment with nafazatrom did not affect the decreased pulmonary removal of [ 3 H]‐PGE 1 , exacerbated the haemodynamic response, reduced survival and potentiated the increase in circulating 6‐keto‐PGF 1α . 4 We conclude that indomethacin acts to prevent the depression of pulmonary [ 3 H]‐PGE 1 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.