Low doses of nitrite, close to physiological levels, increase blood flow in normal and ischemic tissues through a nitric oxide (NO) dependent mechanism. Given that nitrite therapy and dietary supplementation with vegetables high in nitrate (e.g. beets) are gaining popularity we decided to determine if low doses of nitrite impact the development of choroidal neovascularization (CNV), a key feature of wet age related macular degeneration (AMD). Sodium nitrite (at 50 mg/L, 150 mg/L, and 300 mg/L), nitrate (1 g/L) or water alone were provided in the drinking water of C57BL/6 J mice aged 2 or 12 months. Mice were allowed to drink ad libitum for 1 week at which time laser-induced choroidal neovascularization (L-CNV) was induced. The mice continued to drink the supplemented water ad libitum for a further 14 days at which point optical coherence tomography (OCT) was performed to determine the volume of the CNV lesion. Blood was drawn to determine nitrite and nitrate levels and eyes taken for histology. CNV volume was 2.86 × 10⁷ μm³ (±0.4 × 10⁷) in young mice on water alone but CNV volume more than doubled to >6.9 × 10⁷ μm³ (±0.8 × 10⁷) in mice receiving 300 mg/L nitrite or 7.34 × 10⁷ μm³ (±1.4 × 10⁷) in 1 g/L nitrate (p < 0.01). A similar trend was observed in older mice. CNV volume was 5.3 × 10⁷ μm³ (±0.5 × 10⁷) in older mice on water alone but CNV volume almost doubled to approximately 9.3 × 10⁷ μm³ (±1.1 × 10⁷) in mice receiving 300 mg/L nitrite or 8.7 × 10⁷ μm³ (±0.9 × 10⁷) 1 g/L nitrate (p < 0.01). Plasma nitrite levels were highest in young mice receiving 150 mg/L in the drinking water with no changes in plasma nitrate observed. In older mice, drinking water nitrite did not significantly change plasma nitrite, but plasma nitrate was increased. Plasma nitrate was elevated in both young and old mice provided with nitrate supplemented drinking water. Our data demonstrate that the CNV lesion is larger in older mice compared to young and that therapeutic levels of oral nitrite increase the volume of CNV lesions in both young and older mice. Therapeutic nitrite or nitrate supplementation should be used with caution in the elderly population prone to CNV.

接近生理水平的低剂量亚硝酸盐通过一氧化氮 (NO) 依赖机制增加正常和局部缺血组织的血流量。鉴于亚硝酸盐疗法和富含硝酸盐的蔬菜（如甜菜）的膳食补充剂越来越受欢迎，我们决定确定低剂量的亚硝酸盐是否会影响脉络膜新生血管形成 (CNV) 的发展，这是湿性年龄相关性黄斑变性 (AMD) 的一个关键特征. 在 2 个月或 12 个月大的 C57BL/6 J 小鼠的饮用水中单独提供亚硝酸钠（50 mg/L、150 mg/L 和 300 mg/L）、硝酸盐（1 g/L）或水。允许小鼠随意饮水 1 周，此时诱导激光诱导的脉络膜新生血管形成 (L-CNV)。小鼠继续随意饮用补充水 14 天，此时进行光学相干断层扫描 (OCT) 以确定 CNV 病变的体积。抽血以确定亚硝酸盐和硝酸盐水平，并对眼睛进行组织学检查。CNV 体积为 2.86 × 10⁷  μm ^{3 (} ± 0.4 × 10  7 ^)在仅靠水的年轻小鼠中，但在接受 300 mg/L 亚硝酸盐或 7.34 × ^{10 7} 1 g/L 硝酸盐中的 μm ³ (±1.4 × 10 ^{7 ) (p < 0.01)。}在年长小鼠中观察到类似的趋势。仅靠水的老年小鼠的CNV 体积为 5.3 × 10 ⁷  μm ³ (±0.5 × 10 ⁷ )，但在接受 300 mg/L 亚硝酸盐的小鼠中，CNV 体积几乎翻了一番，达到约 9.3 × 10 ⁷  μm ³ (±1.1 × 10 ⁷ )或 8.7 × 10 ⁷ μm ³ (±0.9 × 10 ⁷ ) 1 g/L 硝酸盐 (p < 0.01)。接受 150 mg/L 饮用水的幼鼠血浆亚硝酸盐水平最高，未观察到血浆硝酸盐变化。在老年小鼠中，饮用亚硝酸盐的水并没有显着改变血浆亚硝酸盐，但血浆硝酸盐增加了。在提供补充硝酸盐的饮用水中，年轻和年老小鼠的血浆硝酸盐含量均升高。我们的数据表明，与年轻小鼠相比，老年小鼠的 CNV 病变更大，口服亚硝酸盐的治疗水平会增加年轻和老年小鼠的 CNV 病变体积。对于易患 CNV 的老年人群，应谨慎使用治疗性亚硝酸盐或硝酸盐补充剂。