Malate and Aspartate Increase L-Arginine and Nitric Oxide and Attenuate Hypertension

被引：74

作者：

Hou, Entai ^{[1
]}

Sun, Na ^{[1
]}

Zhang, Fuchang ^{[1
]}

Zhao, Chenyang ^{[1
]}

Usa, Kristie ^{[2
]}

Liang, Mingyu ^{[2
]}

Tian, Zhongmin ^{[1
]}

机构：

[1] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Minist Educ, Key Lab Biomed Informat Engn, Xian 710049, Peoples R China

[2] Med Coll Wisconsin, Ctr Syst Mol Med, Dept Physiol, Milwaukee, WI 53226 USA

来源：

CELL REPORTS | 2017年 / 19卷 / 08期

基金：

中国国家自然科学基金;

关键词：

SALT-SENSITIVE RATS; BLOOD-PRESSURE CONTROL; RENAL-DISEASE; AMINO-ACIDS; DERIVATIZATION; MITOCHONDRIAL; PLASMA; SUPPLEMENTATION; COMPLICATIONS; SPECTROMETRY;

D O I：

10.1016/j.celrep.2017.04.071

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. The Dahl salt-sensitive (SS) rat, a model of salt-sensitive hypertension, exhibits fumarase insufficiencies. To investigate the mechanism mediating the effect of fumarase-related metabolites on hypertension, we considered the pathway in which L-malate can be converted to oxaloacetate, aspartate, argininosuccinate, and L-arginine, the substrate of nitric oxide (NO) synthase. The levels of aspartate, citrulline, L-arginine, and NO were significantly decreased in the kidneys of SS rats compared to salt-insensitive consomic SS.13(BN) rats. Knockdown of fumarase in human kidney cells and vascular endothelial cells resulted in decreased levels of malate, aspartate, L-arginine, and NO. Supplementation of aspartate or malate increased renal levels of L-arginine and NO and attenuated hypertension in SS rats. These findings reveal a multi-step metabolic pathway important for hypertension in which malate and aspartate may modulate blood pressure by altering levels of L-arginine and NO.

引用

页码：1631 / 1639

页数：9

共 40 条

[1] Combined Metabonomic and Quantitative Real-Time PCR Analyses Reveal Systems Metabolic Changes of Fusarium graminearum Induced by Tri5 Gene Deletion [J].