Chen Meng, Zeng Li, Chen Xiangbo, Chen Lan, Gao Di, Yang Zhe, Tian Zhongmin
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaan xi, China.
College of Medical Technology and Engineering, Henan University of Science and Technology, Luo Yang, China.
Acta Physiol (Oxf). 2025 Jul;241(7):e70070. doi: 10.1111/apha.70070.
Circulating branched-chain amino acids (BCAAs) have been widely found to be associated with the risk of hypertension, but mechanisms remain unclear. In this study, we hypothesized that BCAAs could alleviate the development of salt-induced hypertension in Dahl salt-sensitive (SS) rats. The objective was to explore whether long-term high-salt diets (a major dietary risk for high blood pressure) alter BCAAs levels in SS rats and how dietary BCAAs influence salt-induced hypertension.
SS rats received an 11-week dietary intervention to investigate the effects of dietary BCAAs on SS hypertension. Metabolic changes were studied using GC-MS and LC-MS/MS, as well as selected enzyme activity measurements. Western blotting was used to measure the protein levels of p-BCKDHA/BCKDHA and AQP. HUVECs and HK-2 cells were treated with 2 mM BCAAs for 24 h before measuring metabolites and enzyme activities.
An 11-week high-salt diet increased blood pressure in SS rats, which was accompanied by reduced circulating BCAAs levels. Dietary BCAAs attenuated salt-induced hypertension, restored circulating BCAAs levels, and enhanced BCAAs metabolic activity. It also decreased aquaporin-1 (AQP1) levels in the renal cortex, promoting water and sodium excretion and improving renal function in SS rats. Additionally, metabolomic analysis demonstrated that dietary BCAAs enhanced arginine-NO metabolism in the kidneys and thoracic aorta of SS rats, promoting NOS-mediated NO synthesis and improving vasodilation. The promotion of NO synthesis by BCAAs was confirmed at the cellular level.
Long-term BCAAs intake promoted water and sodium excretion, enhanced NO synthesis in kidneys and thoracic aortas, and lowered blood pressure in SS rats on a high-salt diet, suggesting BCAAs may improve SS hypertension rather than exacerbate it.
循环支链氨基酸（BCAAs）已被广泛发现与高血压风险相关，但其机制仍不清楚。在本研究中，我们假设BCAAs可以减轻盐敏感性（SS）大鼠盐诱导的高血压发展。目的是探讨长期高盐饮食（高血压的主要饮食风险因素）是否会改变SS大鼠体内BCAAs水平，以及饮食中的BCAAs如何影响盐诱导的高血压。
对SS大鼠进行为期11周的饮食干预，以研究饮食中BCAAs对SS大鼠高血压的影响。使用气相色谱-质谱联用仪（GC-MS）和液相色谱-串联质谱仪（LC-MS/MS）以及选定的酶活性测量方法研究代谢变化。采用蛋白质免疫印迹法测量磷酸化的支链α-酮酸脱氢酶E1α亚基/支链α-酮酸脱氢酶E1α亚基（p-BCKDHA/BCKDHA）和水通道蛋白（AQP）的蛋白质水平。在用2 mM BCAAs处理人脐静脉内皮细胞（HUVECs）和人近端肾小管上皮细胞（HK-2细胞）24小时后，测量代谢产物和酶活性。
为期11周的高盐饮食使SS大鼠血压升高，同时循环BCAAs水平降低。饮食中的BCAAs减轻了盐诱导的高血压，恢复了循环BCAAs水平，并增强了BCAAs代谢活性。它还降低了肾皮质中水通道蛋白-1（AQP1）的水平，促进水和钠排泄，改善了SS大鼠的肾功能。此外，代谢组学分析表明，饮食中的BCAAs增强了SS大鼠肾脏和胸主动脉中的精氨酸-一氧化氮（NO）代谢，促进了一氧化氮合酶（NOS）介导的NO合成并改善了血管舒张。BCAAs对NO合成的促进作用在细胞水平上得到了证实。
长期摄入BCAAs促进了水和钠排泄，增强了肾脏和胸主动脉中的NO合成，并降低了高盐饮食的SS大鼠的血压，表明BCAAs可能改善SS大鼠的高血压，而不是加剧高血压。
