NOS II inhibition restores attenuation of endothelium-dependent hyperpolarization in rat mesenteric artery exposed to lipopolysaccharide.
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 formation 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 diethylamine 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.
Mitsumizo
Shinji
S
Department of Anesthesiology and Critical Care Medicine, Surgical Center, Saga Medical School, Saga, Japan.
Nakashima
Mikio
M
Hamada
Tomoko
T
Totoki
Tadahide
T
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II