Endotoxin-induced impairment of vascular reactivity in the pithed rat: role of arachidonic acid metabolites.

The effect of endotoxin on vascular reactivity was studied in pithed rats. Endotoxin infusion (1 mg kg-1 h-1) impaired pressor responses to noradrenaline, angiotensin II, BAY K 8644, and stimulation of the spinal sympathetic outflow. The loss of reactivity was prevented by pretreatment with the cyclooxygenase inhibitor flurbiprofen or the dual cyclooxygenase/lipoxygenase inhibitor BW755C. The effect of endotoxin in impairing vascular reactivity to noradrenaline was mimicked by prostaglandin E2 and platelet-activating factor but not by the prostacyclin analogue iloprost. Platelet-activating factor also impaired responsiveness to sympathetic stimulation. These results suggest a role for cyclooxygenase products and, possibly, platelet-activating factor in endotoxin-induced impairment of vascular reactivity.