Differential changes in end organ immune cells and inflammation in salt-sensitive hypertension: effects of lowering blood pressure.

IF 6.7 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Shobana Navaneethabalakrishnan, Bethany L Goodlett, Hannah L Smith, Alyssa Cardenas, Asia Burns, Brett M Mitchell
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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.

盐敏感性高血压终末器官免疫细胞和炎症的不同变化:降低血压的影响
我们曾报道盐敏感性高血压(SSHTN)与雌雄小鼠肾脏和性腺中促炎免疫细胞、炎症和炎症相关淋巴管生成增加有关。 然而,目前还不清楚这些对终末器官的不利影响是由血压(BP)升高、盐分水平升高还是两者共同作用造成的。 我们假设,药物降低血压并不能完全缓解与 SSHTN 相关的肾脏和性腺免疫细胞积聚、炎症和淋巴管生成。 通过在雌雄 C57BL6/J 小鼠的饮用水中加入硝基-L-精氨酸甲酯盐酸盐(L-NAME;0.5 mg/mL)诱导 SSHTN 2 周,然后进行 2 周的冲洗。 随后,小鼠接受为期 3 周的 4% 高盐饮食(SSHTN)。 治疗组采用相同的 SSHTN 诱导方案,但在饮食阶段(SSHTN+HYD)在饮用水中加入水拉嗪(HYD;250 毫克/升)。对照组小鼠接受自来水和标准饮食 7 周。 除了降低收缩压外,HYD 治疗还普遍减少了促炎免疫细胞以及 SSHTN 小鼠肾脏和性腺中的炎症。 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,并改善了其肾脏和性腺功能。 这些数据证明了高系统压力和盐对终末器官免疫细胞的不同作用,有助于人们更广泛地了解血压和盐摄入量是如何共同影响免疫反应的,并突出了靶向治疗干预的意义。
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来源期刊
Clinical science
Clinical science 医学-医学:研究与实验
CiteScore
11.40
自引率
0.00%
发文量
189
审稿时长
4-8 weeks
期刊介绍: Translating molecular bioscience and experimental research into medical insights, Clinical Science offers multi-disciplinary coverage and clinical perspectives to advance human health. Its international Editorial Board is charged with selecting peer-reviewed original papers of the highest scientific merit covering the broad spectrum of biomedical specialities including, although not exclusively: Cardiovascular system Cerebrovascular system Gastrointestinal tract and liver Genomic medicine Infection and immunity Inflammation Oncology Metabolism Endocrinology and nutrition Nephrology Circulation Respiratory system Vascular biology Molecular pathology.
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