PDF(Pubmed)
Abstract：
We reported that salt-sensitive hypertension (SSHTN) is associated with increased pro-inflammatory immune cells, inflammation, and inflammation-associated lymphangiogenesis in the kidneys and gonads of male and female mice. However, it is unknown whether these adverse end organ effects result from increased blood pressure (BP), elevated levels of salt, or both. We hypothesized that pharmaceutically lowering BP would not fully alleviate the renal and gonadal immune cell accumulation, inflammation, and lymphangiogenesis associated with SSHTN. SSHTN was induced in male and female C57BL6/J mice by administering nitro-L-arginine methyl ester hydrochloride (L-NAME; 0.5 mg/ml) in their drinking water for 2 weeks, followed by a 2-week washout period. Subsequently, the mice received a 3-week 4% high salt diet (SSHTN). The treatment group underwent the same SSHTN induction protocol but received hydralazine (HYD; 250 mg/L) in their drinking water during the diet phase (SSHTN+HYD). Control mice received tap water and a standard diet for 7 weeks. In addition to decreasing systolic BP, HYD treatment generally decreased pro-inflammatory immune cells and inflammation in the kidneys and gonads of SSHTN mice. Furthermore, the decrease in BP partially alleviated elevated renal and gonadal lymphatics and improved renal and gonadal function in mice with SSHTN. These data demonstrate that high systemic pressure and salt differentially act on end organ immune cells, contributing to the broader understanding of how BP and salt intake collectively shape immune responses and highlight implications for targeted therapeutic interventions.
摘要：
我们报道了盐敏感性高血压（SSHTN）与促炎免疫细胞增加有关，炎症,以及雄性和雌性小鼠肾脏和性腺中与炎症相关的淋巴管生成。然而,尚不清楚这些不良的终末器官效应是否由血压升高（BP）引起，盐含量升高，或者两者兼而有之。我们假设药物降低血压不会完全减轻肾脏和性腺免疫细胞的积累，炎症,和与SSHTN相关的淋巴管生成。通过在饮用水中施用硝基-L-精氨酸甲酯盐酸盐（L-NAME;0.5mg/mL），在雄性和雌性C57BL6/J小鼠中诱导SSHTN，接下来是2周的冲洗期。随后，小鼠接受3周4%高盐饮食(SSHTN)。治疗组经历相同的SSHTN诱导方案,但在饮食阶段(SSHTN+HYD)期间在其饮用水中接受肼屈嗪(HYD;250mg/L)。对照小鼠接受自来水和标准饮食7周。除了降低收缩压,HYD治疗通常减少SSHTN小鼠的肾脏和性腺中的促炎免疫细胞和炎症。此外，血压的降低部分缓解了SSHTN小鼠肾脏和性腺淋巴管的升高，并改善了肾脏和性腺功能。这些数据表明，高全身压力和盐差异作用于终末器官免疫细胞，有助于更广泛地了解BP和盐摄入量如何共同影响免疫反应，并强调对有针对性的治疗干预措施的影响。
