Faculty Collaboration Database

Malate and Aspartate Increase L-Arginine and Nitric Oxide and Attenuate Hypertension. Cell Rep 2017 May 23;19(8):1631-1639

Date

05/26/2017

Pubmed ID

28538181

DOI

10.1016/j.celrep.2017.04.071

Scopus ID

2-s2.0-85019652468 (requires institutional sign-in at Scopus site)   63 Citations

Abstract

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.

Author List

Hou E, Sun N, Zhang F, Zhao C, Usa K, Liang M, Tian Z

MESH terms used to index this publication - Major topics in bold

Animals
Arginine
Aspartic Acid
Down-Regulation
Fumarate Hydratase
Gene Knockdown Techniques
Hypertension
Kidney
Malates
Nitric Oxide
Rats, Inbred Dahl