PMID:15637112

Citation	Yan, C, Huang, A, Wu, Z, Kaminski, PM, Wolin, MS, Hintze, TH, Kaley, G and Sun, D (2005) Increased superoxide leads to decreased flow-induced dilation in resistance arteries of Mn-SOD-deficient mice. Am. J. Physiol. Heart Circ. Physiol. 288:H2225-31
Abstract	The role of mitochondrial manganese-superoxide dismutase (Mn-SOD) in the maintenance of vascular function has not yet been studied. Thus we examined flow- and agonist-induced dilations in isolated mesenteric arteries (approximately 90 microm in diameter) of Mn-SOD heterozygous (Mn-SOD+/-) and wild-type (WT) mice. Increases in flow elicited dilations in all vessels, but the magnitude of the dilation was significantly less in vessels of Mn-SOD+/- mice than in those of WT mice (64 vs. 74% of passive diameter). N(omega)-nitro-L-arginine methyl ester inhibited the dilation in vessels of WT mice but had no effect on vessels of Mn-SOD+/- mice. Tempol or tiron (superoxide scavengers) increased flow-induced dilation in vessels of Mn-SOD+/- mice. Acetylcholine- and sodium nitroprusside-induced, but not adenosine-induced, dilations were also decreased in arteries of Mn-SOD+/- mice. Superoxide levels in the arteries of Mn-SOD+/- mice were significantly increased. Western blot analysis confirmed a 50% reduction of Mn-SOD protein in the vessels of Mn-SOD+/- mice. A 41% reduction in endothelial nitric oxide synthase (eNOS) protein and a 37% reduction in eNOS activity were also found in the vessels of Mn-SOD+/- mice. Whereas there was no difference in eNOS protein in kidney homogenates of WT and Mn-SOD+/- mice, a significant reduction of nitric oxide synthase activity was found in Mn-SOD+/- mice, which could be restored by the administration of tiron. We conclude that an increased concentration of superoxide due to reduced activity of Mn-SOD, which inactivates nitric oxide and inhibits eNOS activity, contributes to the impaired vasodilator function of isolated mesenteric arteries of Mn-SOD+/- mice. These results suggest that Mn-SOD contributes significantly to the regulation of vascular function.
Links	PubMed Online version:10.1152/ajpheart.01036.2004
Keywords	Animals; Endothelium, Vascular/enzymology; Gene Expression Regulation, Enzymologic/physiology; Male; Mesenteric Arteries/physiology; Mice; Mice, Mutant Strains; Nitric Oxide Synthase/genetics; Nitric Oxide Synthase/metabolism; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Regional Blood Flow/physiology; Stress, Mechanical; Superoxide Dismutase/genetics; Superoxide Dismutase/metabolism; Superoxides/metabolism; Vasodilation/drug effects; Vasodilation/physiology; Vasodilator Agents/pharmacology
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.