THE POSSIBLE ROLES OF HISTAMINE, 5-HYDROXYTRYPTAMINE AND PROSTAGLANDIN F2α AS MEDIATORS OF THE ACUTE PULMONARY EFFECTS OF ENDOTOXIN

Abstract

1 In an attempt to investigate the possible role of released vasoactive substances in mediating the pulmonary pressor responses to E. coli endotoxin, cats were pretreated with histamine, 5-hydroxytryptamine (5-HT) or prostaglandin antagonists, with a histamine depleting agent (compound 48/80) or with an inhibitor of prostaglandin synthetase (sodium meclofenamate). 2 The administration of endotoxin (2 mg/kg) resulted in a rapidly developing pulmonary hypertension (pressure twice normal after 2–3 min), increases in right atrial and intratracheal pressures, systemic hypotension and bradycardia. These effects were unaffected by methysergide in a dose sufficient to prevent the effects of intravenously administered 5-HT. 3 Endotoxin responses were also unaffected by a combination of mepyramine and burimamide in doses sufficient to reduce markedly the effects of intravenously-administered histamine. In cats pretreated (chronically or acutely) with compound 48/80, endotoxin induced a transient pulmonary pressor response which was not maintained. 4 The pulmonary and systemic responses to endotoxin were prevented by the prior administration of the prostaglandin antagonist, polyphloretin phosphate and by pretreatment with the prostaglandin synthetase inhibitor, sodium meclofenamate. 5 It is concluded that a pulmonary vasoconstrictor prostaglandin is involved in the acute response to endotoxin in the cat.