THE EFFECT OF ENDOTOXIN ON SYMPATHETIC RESPONSES IN THE RAT ISOLATED-PERFUSED MESENTERIC BED - INVOLVEMENT OF NITRIC-OXIDE AND CYCLOOXYGENASE PRODUCTS

1 The effects of endotoxin on the vasoconstrictor responses to sympath etic nerve stimulation (SNS) were investigated in the rat isolated per fused mesenteric bed. 2 Rats received either saline (0.1 ml h(-1)) or endotoxin (2.5 mg kg(-1) h(-1)) intravenously for 4 h; the mesenteric beds were then isolated, perfused with Krebs and prepared for SNS (50 V, 3 ms, 7-40 Hz). 3 SNS caused a frequency-dependent vasoconstrictor response which was abolished by either tetrodotoxin (10(-7) M), prazos in (2.4 x 10(-7)M) or guanethidine (2.4 x 10(-7) M). 4 In mesenteric v ascular beds removed from rats infused with endotoxin, there were mark edly impaired vasoconstrictor responses to SNS, although responses to noradrenaline were not modified. 5 Removal of the endothelium with dis tilled water prevented endotoxin-induced impairment of vasoconstrictor responses to SNS, without modifying these responses in preparations f rom control rats. 6 Pretreatment with dexamethasone (3 mg kg(-1) i.p. Ih before commencing endotoxin or saline infusions) did not modify res ponses to SNS in control rats but prevented the effects of endotoxin. 7 Both L-NAME (10(-3) M) and indomethacin (10(-5) M) restored response s to SNS in preparations from endotoxin-treated rats without modifying these responses in control preparations. However, coadministration of L-NAME and indomethacin markedly augmented responses in both control and endotoxin-treated preparations. 8 The effects of L-NAME were rever sed by addition of L-arginine (10(-3) M). 9 The data suggest that endo toxin impairs the release of noradrenaline and that this effect is sec ondary to increased production of nitric oxide and prostanoids, possib ly by the endothelium.