Hall S, Turcato S, Clapp L
Rayne Institute, St. Thomas' Hospital, London, United Kingdom.
Biochem Biophys Res Commun. 1996 Jul 5;224(1):184-90. doi: 10.1006/bbrc.1996.1005.
We have examined the role of K+ channels in mediating vasorelaxation produced by bacterial lipopolysaccharide (LPS) in endothelial-denuded strips of rat aorta precontracted with phenylephrine (1 microM). Salmonella typhosa LPS (0.1 microgram/ml) caused significant relaxation of tension which peaked at approximately 4hr. The K+ channel blocker, tetraethylammonium chloride (TEA; 10 mM), fully reversed these relaxations whether applied before or after long term exposure to LPS. L-arginine, the substrate for nitric oxide synthase, caused large relaxations in tissues incubated with LPS that were markedly inhibited by TEA. In contrast, TEA or L-arginine had little effect on phenylephrine contractions in control tissues. Furthermore, the inducible nitric oxide synthase inhibitor, aminoguanidine (0.4 mM), reversed the effects of LPS and blocked responses to TEA. These results suggest that activation of K+ channels, possibly Ca-activated K+ channels, through induction of the nitric oxide synthase pathway, may well be responsible for endotoxin-mediated hyporeactivity to vasoconstrictor agents in vascular smooth muscle.
我们研究了钾离子通道在介导细菌脂多糖（LPS）引起的血管舒张中的作用，该实验以用去氧肾上腺素（1微摩尔）预收缩的大鼠主动脉内皮剥脱条为研究对象。鼠伤寒沙门氏菌脂多糖（0.1微克/毫升）引起显著的张力松弛，在约4小时达到峰值。钾离子通道阻滞剂氯化四乙铵（TEA；10毫摩尔），无论在长期暴露于LPS之前还是之后应用，均可完全逆转这些松弛作用。一氧化氮合酶的底物L-精氨酸，在与LPS一起孵育的组织中引起较大的松弛，且这种松弛被TEA显著抑制。相比之下，TEA或L-精氨酸对对照组织中的去氧肾上腺素收缩作用影响很小。此外，诱导型一氧化氮合酶抑制剂氨基胍（0.4毫摩尔）可逆转LPS的作用并阻断对TEA的反应。这些结果表明，通过诱导一氧化氮合酶途径激活钾离子通道，可能是钙激活的钾离子通道，很可能是血管平滑肌中内毒素介导的对血管收缩剂反应性降低的原因。
