ABNORMAL ACTIVATION OF K+ CHANNELS UNDERLIES RELAXATION TO BACTERIAL LIPOPOLYSACCHARIDE IN RAT AORTA

We have examined the role of K+ channels in mediating vasorelaxation p roduced by bacterial lipopolysaccharide (LPS) in endothelial-denuded s trips of rat aorta precontracted with phenylephrine (1 mu M). Salmonel la typhosa LPS (0.1 mu g/ml) caused significant relaxation of tension which peaked at similar to 4hr, The K+ channel blocker, tetraethylammo nium chloride (TEA; 10 mM), fully reversed these relaxations whether a pplied before or after long term exposure to LPS. L-arginine, the subs trate for nitric oxide synthase, caused large relaxations in tissues i ncubated with LPS that were markedly inhibited by TEA. In contrast, TE A or L-arginine had little effect on phenylephrine contractions in con trol tissues. Furthermore, the inducible nitric pride synthase inhibit or, aminoguanidine (0.4 mM), reversed the effects of LPS and blocked r esponses to TEA. These results suggest that activation of K+ channels, possibly Ca-activated K+ channels, through induction of the nitric ox ide synthase pathway, may well be responsible for endotoxin-mediated h yporeactiv ity to vasoconstrictor agents in vascular smooth muscle. (C ) 1996 Academic Press, Inc.