[Decrease of the hypertensive responses to phenylephrine in the rat submitted to a sublethal dose of E. coli...

E. Coli endotoxin was injected by i.v. route to rats at a dose immediately lower than the minimal lethal dose. Assays were performed on anesthetized rats (urethane 1 g/kg i.p.). The carotid arterial pressure was recorded 1, 2, 4, 16 and 24 hours after endotoxin administration, and hypertensive responses to three successive doses of phenylephrine (2; 5 or 10 micrograms/kg i.v.) was measured until return to initial values. Compared to control rats the hypertensive responses in the endotoxin-treated rats were depressed. This depression was evident at the first hour following endotoxin administration and was maintained at least for four hours. This lower response was improved by a treatment of the rats with indomethacin (10 mg/kg i.v.) when this drug was administered half an hour before, or concomitantly with endotoxin. When indomethacin (10 mg/kg) was given two hours after endotoxin the improvement was less marked. So did indomethacin at 5 mg/kg dose level. Indomethacin alone did not potentiate the pressive responses to phenylephrine. These results show that the endotoxin-induced decrease in the hypertensive responses to phenylephrine does not appear to depend on its hypotensive or lethal effects. It can be brought together with the low cardiovascular responses to different drugs found in animals under endotoxin shock. These results show moreover that an early increase in prostaglandin synthesis under the influence of endotoxin may be involved in this depressant effect.