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.
Gray
G A
GA
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland.
Furman
B L
BL
Parratt
J R
JR
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone / Q000494:pharmacology; D004558:Electric Stimulation; D004731:Endotoxins / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology; D005480:Flurbiprofen / Q000494:pharmacology; D006439:Hemodynamics; D016285:Iloprost; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D010972:Platelet Activating Factor; D000804:Angiotensin II; D016718:Arachidonic Acid; D005480:Flurbiprofen; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D016285:Iloprost; D015232:Dinoprostone; D009638:Norepinephrine