Reduced endothelial dependent vasodilation in vessels from TLR4(-/-) mice is associated with increased superoxide generation.
Bottom Line: Using the isometric wire myograph, mesenteric artery vasodilator responses to acetylcholine and MnCl(2) (a superoxide dismutase mimetic) were measured.Our observations suggest that loss of TLR4 increases superoxide generation which reduces the biological activity of endothelial derived nitric oxide and thereby explains the endothelial dysfunction and associated cardiovascular phenotype in TLR4(-/-) mice.These data implicate a novel cardio-protective role for TLR4 in vascular homeostasis.
Affiliation: Cardiothoracic Pharmacology, NHLI, Imperial College, Dovehouse Street, London, UK. email@example.comShow MeSH
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Mentions: In parallel experiments superoxide levels in the endothelial cell (Fig. 3) and smooth muscle cell (Fig. 4) layers of mesenteric arteries were visualised and quantified in vessels from wild type and TLR4−/− mice. In vessels from wild type mice, superoxide levels were relatively low and not significantly inhibited by MnCl2. By contrast levels of superoxide were greatly increased in both endothelial cell and smooth muscle cell layers in arteries from TLR4−/− mice and reduced to control levels in the presence of MnCl2 (Figs. 3 and 4).
Affiliation: Cardiothoracic Pharmacology, NHLI, Imperial College, Dovehouse Street, London, UK. firstname.lastname@example.org