Effect of Win 44441-3 and naloxone on endotoxin-induced hypotensive shock in anesthetized hypertensive rats

A model of endotoxin-induced shock was developed in anesthetized spontaneously hypertensive rats. E. coli lipopolysaccharide (13 mg/kg i.v.) reduced systolic and diastolic blood pressure by at least 51 mm Hg in 80-90% of rats. Naloxone (1.25-10.0 mg/kg i.v.) partially restored blood pressure of hypotensive rats for 6-15 minutes after injection. Win 44441-3 (0.25-2.0 mg/kg i.v.) raised blood pressure for 3-12 minutes after injection. Ten minute pretreatment with naloxone (10 mg/kg i.v.) or Win 44441-3 (0.5 mg/kg i.v.) did not appreciably reduce the hypotensive effect of E. coli lipopolysaccharide. This model is a rapid and convenient bioassay for evaluating the effects of opioid antagonists in endotoxin shock. In this model naloxone and Win 44441-3 exhibited beneficial effects but a prolonged duration of action of the Win compound over naloxone was not observed.