THE ANTIOXIDANT, U74389, AMELIORATES THE DEPRESSION OF VASCULAR REACTIVITY CAUSED BY LIPOPOLYSACCHARIDE

There is growing evidence that an oxidant stress contributes to the de leterious effects of bacterial lipopolysaccharide (LPS). The present s tudy evaluated the ability of the antioxidant, U74389, to prevent the depression of vascular reactivity caused by LPS. Aortic rings taken fr om rats given LPS showed a depression of maximum force in response to phenylephrine that was reversed by an inhibitor of nitric oxide syntha se. Pretreatment of animals with U74389 attenuated this depression of vascular reactivity. U74389 did not limit the increase in serum tumor necrosis factor levels caused by LPS. These results show that U74389 c an ameliorate the depression of vascular reactivity caused by LPS poss ibly by interfering with the induction of nitric oxide synthase.