高盐 (HS) 摄入会诱发对一氧化氮 (NO) 抑制的增强高血压反应，但在一氧化氮完整状态下，它会导致血压 (BP) 发生微小变化。这种增强的原因尚不清楚。 HS 诱导肿瘤坏死因子-α (TNFα) 产生，通过激活其 1 型受体 (TNFR1) 引起尿钠排泄。我们假设 NO 缺乏会降低肾 TNFR1 活性，导致钠潴留和高血压增加。我们检查了野生型小鼠 (WT, C57BL6) 摄入 HS (4% NaCl) 后肾脏 TNFR1 蛋白表达的变化（免疫组织化学分析）。使用一氧化氮合酶 (NOS) 抑制剂硝基-L-精氨酸甲酯（L-NAME；0.05 mg/min/g；渗透微型泵）以及内皮型一氧化氮合酶敲除小鼠 (eNOSKO) 进行实验，并比较了WT 小鼠摄入正常盐（NS；0.3% NaCl）。使用尾套体积描记法测量血压，并使用代谢笼收集 24 小时尿液。单独使用 HS 不会改变未治疗小鼠的平均血压（76±3 至 77±1 mmHg），但在 L-NAME 治疗中诱导增强反应(106±1 vs 97±2 mmHg) 和 eNOSKO (107±2 vs 89±3 mmHg) 小鼠。 WT HS 小鼠肾组织中 TNFR1 表达面积百分比 (4.1±0.5%) 高于 WT NS 小鼠 (2.7±0.6%)。然而，L-NAME处理的WT NS (0.9±0.1%)和eNOSKO NS (1.4±0.2%)中的TNFR1表达显着低于WT NS和WT HS小鼠。这些数据表明TNFR1活性在NO中下调缺乏条件，这会促进盐潴留，导致 HS 摄入期间高血压加重。© 作者 2024。由牛津大学出版社代表美国高血压杂志有限公司出版。

High salt (HS) intake induces an augmented hypertensive response to nitric oxide (NO) inhibition, though it causes minimal changes in blood pressure (BP) in NO intact condition. The cause of such augmentation is not known. HS induces tumor necrosis factor-alpha (TNFα) production that causes natriuresis via activation of its' receptor type 1 (TNFR1). We hypothesized that NO deficiency reduces renal TNFR1 activity, leading to enhanced sodium retention and hypertension.We examined the changes in renal TNFR1 protein expression (Immunohistochemistry analyses) after HS (4% NaCl) intake in wild-type mice (WT, C57BL6) treated with a NO synthase (NOS) inhibitor, nitro-L-arginine methyl ester (L-NAME; 0.05 mg/min/g; osmotic mini-pump), as well as in endothelial NOS knockout mice (eNOSKO) and compared the responses in WT mice with normal salt (NS; 0.3% NaCl) intake. BP was measured with tail-cuff plethysmography and 24-hour urine collections were made using metabolic cages.HS alone did not alter mean BP in untreated mice (76±3 to 77±1 mmHg) but induced an augmented response in L-NAME treated (106±1 vs 97±2 mmHg) and in eNOSKO (107±2 vs 89±3 mmHg) mice. The percentage area of TNFR1 expression in renal tissue was higher in WT+HS (4.1 + 0.5%) than in WT+NS mice (2.7±0.6%). However, TNFR1 expression was significantly lower in L-NAME treated WT+NS (0.9±0.1%) and in eNOSKO+NS (1.4±0.2%) than in both WT+NS and WT+HS mice.These data indicate that TNFR1 activity is downregulated in NO deficient conditions, which facilitates salt retention leading to augmented hypertension during HS intake.© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.