Blood levels of 6-oxo-prostaglandin F 1α during endotoxin-induced hypotension in rabbits

Abstract

Levels of 6-oxo-prostaglandin F 1α (6-oxo-PGF 1α), the non-enzymic degradation product of prostacyclin, were measured in arterial blood from anaesthetized rabbits, befor and after intravenous (i.v) administration of endotoxin (Lipopolysaccharide W.E. coli 0111:B4, 5 mg/kg). 6-Oxo-PGF 1α was assessed by radioimmunoassay after extraction and separation by thin-layer chromatography. The basal concentration of 6-oxo-PGF 1α in blood was less than 100 pg/ml in 19 out of 20 rabbits. This indicates that the level of circulating prostacyclin is generally below 100 pg/ml. The administration of endotoxin induced a biphasic hypotension, and increased levels of 6-oxo-PGF 1α were found in all endotoxin-treated animals during the secondary hypotension after 60 and 120 min. Pretreatment with indomethacin (2.5 mg/kg) prevented the secondary fall in arterial blood pressure and significantly suppressed the rise in 6-oxo-PGF 1α. However, indomethacin failed to alter the endotoxin-induced thrombocytopenia and did not modify the endotoxin-induced platelet aggregation in vitro. It is concluded that prostacyclin contributed to the secondary hypotension which accompanied the i.v. administration of endotoxin. Thromboxane A 2 seems not to be of primary importance in the endotoxin-platelet interaction.