NOSII inhibition restores attenuation of endothelium-dependent hyperpolarization in rat mesenteric artery exposed to lippopolysaccharide

The aim of this study was to assess the effects of lipopolysaccharide (LPS) exposure on the endothelium-dependent hyperpolarization in the rat mesenteric artery using isometric tension recordings and electrophysiological studies. Mesenteric arterial rings of male Sprague-Dawley rats were incubated with LPS for 6 hours. All experiments were performed in the presence of indomethacin to inhibit the fort-nation of vasoactive prostanoids. Contraction to phenylephrine was significantly reduced in rings incubated with LPS, which was restored in the presence of N-omega-nitro-L-arginine methyl ester (L-NAME). L-NAME resistant relaxation to acetylcholine was attenuated in LPS-treated rings. LPS exposure hyperpolarized resting membrane potentials of arterial smooth muscle cells, which was repolarized by incubation with either L-NAME or 1400W, a selective inhibitor of nitric oxide synthase II (NOS II). Endothelium-dependent hyperpolarization to acetylcholine was attenuated in arteries incubated with LPS. while incubation with LPS and 1400W restored EDHF-mediated hyperpolarization. LPS-induced membrane potential change was mimicked by incubation with either SIN-1 or diethylarnine NONOate, a donor of nitric oxide. These data suggest that LPS exposure attenuates EDHF-mediated both relaxation and hyperpolarization in the rat mesenteric artery. The possible mechanisms underlying decreased EDHF-mediated responses might be due to, at least in some part, massive nitric oxide induced by NOS II.