Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging.
Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging.
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DOI：
10.1111/j.1474-9726.2011.00679.x
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发表时间：
2011-06
期刊：
影响因子：
7.8
通讯作者：
Seals DR
中科院分区：
文献类型：
--
作者：
Sindler AL;Fleenor BS;Calvert JW;Marshall KD;Zigler ML;Lefer DJ;Seals DR
我们测试了短期亚硝酸盐治疗逆转血管内皮功能障碍和大弹性动脉硬化的假设，并减少动脉氧化应激和炎症。老年（26-28月龄）雄性C57BL6对照小鼠的动脉、心脏和血浆中亚硝酸盐浓度较低（P< 0.05）， 3周的亚硝酸钠（50 mg L−1饮用水）使亚硝酸盐水平恢复到或高于年轻（4-6月龄）对照。离体老龄小鼠颈动脉内皮依赖性扩张（EDD）由一氧化氮（NO）生物利用度降低介导（71.7±6.1% vs. 93.0±2.0%）降低（P< 0.05），亚硝酸钠通过提高NO生物利用度恢复EDD（95.5±1.6%）。4‐羟基2,2,6,6‐四甲基哌啶1‐氧（TEMPOL），一种超氧化物歧化酶（SOD）模拟物，罗泼宁，一种烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH）抑制剂，和sepapterin（外源性四氢生物terin）都能恢复老龄对照组的EDD对ACh的影响，但对补充亚硝酸盐的老龄小鼠没有影响。老年对照组小鼠主动脉脉波速度增加（478±16比332±12 AU，P< 0.05），亚硝酸盐组降低（384±27 AU）。老年对照小鼠的硝基酪氨酸、超氧化物的产生和NADPH氧化酶的表达增加了~ 100-300%，SOD活性降低了~ 50%（与年轻小鼠相比均p < 0.05），但亚硝酸钠处理能改善这种情况。添加亚硝酸盐后，老龄对照组炎症细胞因子显著升高（P< 0.05），但降低至年轻对照组水平。短期亚硝酸盐治疗可逆转与年龄相关的血管内皮功能障碍、大弹性动脉僵硬、氧化应激和炎症。亚硝酸钠可能是治疗人类动脉老化的一种新疗法。
We tested the hypothesis that short‐term nitrite therapy reverses vascular endothelial dysfunction and large elastic artery stiffening with aging, and reduces arterial oxidative stress and inflammation. Nitrite concentrations were lower (P< 0.05) in arteries, heart, and plasma of old (26–28 month) male C57BL6 control mice, and 3 weeks of sodium nitrite (50 mg L−1in drinking water) restored nitrite levels to or above young (4–6 month) controls. Isolated carotid arteries of old control mice had lower acetylcholine (ACh)‐induced endothelium‐dependent dilation (EDD) (71.7 ± 6.1% vs. 93.0 ± 2.0%) mediated by reduced nitric oxide (NO) bioavailability (P< 0.05 vs. young), and sodium nitrite restored EDD (95.5 ± 1.6%) by increasing NO bioavailability. 4‐Hydroxy‐2,2,6,6‐tetramethylpiperidine 1‐oxyl (TEMPOL), a superoxide dismutase (SOD) mimetic, apocynin, a nicotinamide adenine dinucleotide phosphate‐oxidase (NADPH) inhibitor, and sepiapterin (exogenous tetrahydrobiopterin) each restored EDD to ACh in old control, but had no effect in old nitrite‐supplemented mice. Old control mice had increased aortic pulse wave velocity (478 ± 16 vs. 332 ± 12 AU,P< 0.05 vs. young), which nitrite supplementation lowered (384 ± 27 AU). Nitrotyrosine, superoxide production, and expression of NADPH oxidase were ∼100–300% greater and SOD activity was ∼50% lower in old control mice (allP< 0.05 vs. young), but were ameliorated by sodium nitrite treatment. Inflammatory cytokines were markedly increased in old control mice (P< 0.05), but reduced to levels of young controls with nitrite supplementation. Short‐term nitrite therapy reverses age‐associated vascular endothelial dysfunction, large elastic artery stiffness, oxidative stress, and inflammation. Sodium nitrite may be a novel therapy for treating arterial aging in humans.
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DOI：
10.1016/j.niox.2009.11.001
发表时间：
2010-02-15
期刊：
Nitric oxide : biology and chemistry
影响因子：
--
作者：
Calvert JW;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
37.8
作者：
Dezfulian C;Shiva S;Alekseyenko A;Pendyal A;Beiser DG;Munasinghe JP;Anderson SA;Chesley CF;Vanden Hoek TL;Gladwin MT
通讯作者：
Gladwin MT
DOI：
10.1152/ajpheart.00248.2004
发表时间：
2004-12-01
影响因子：
4.8
作者：
Blackwell, KA;Sorenson, JP;Katusic, ZS
通讯作者：
Katusic, ZS
影响因子：
15.9
作者：
Landmesser, U;Dikalov, S;Harrison, DG
通讯作者：
Harrison, DG
影响因子：
37.8
作者：
Gonzalez, Felix M.;Shiva, Sruti;Arai, Andrew E.
通讯作者：
Arai, Andrew E.