Urinary Metabolites Associated with Blood Pressure on a Low- or High-Sodium Diet. Theranostics 2018;8(6):1468-1480
Date
03/21/2018Pubmed ID
29556335Pubmed Central ID
PMC5858161DOI
10.7150/thno.22018Scopus ID
2-s2.0-85041571500 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
Dietary salt intake has significant effects on arterial blood pressure and the development of hypertension. Mechanisms underlying salt-dependent changes in blood pressure remain poorly understood, and it is difficult to assess blood pressure salt-sensitivity clinically. Methods: We examined urinary levels of metabolites in 103 participants of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial after nearly 30 days on a defined diet containing high sodium (targeting 150 mmol sodium intake per day) or low sodium (50 mmol per day). Targeted chromatography/mass spectrometry analysis was performed in 24 h urine samples for 47 amino metabolites and 10 metabolites related to the tricarboxylic acid cycle. The effect of an identified metabolite on blood pressure was examined in Dahl salt-sensitive rats. Results: Urinary metabolite levels improved the prediction of classification of blood pressure salt-sensitivity based on race, age and sex. Random forest and generalized linear mixed model analyses identified significant (false discovery rate <0.05) associations of 24 h excretions of β-aminoisobutyric acid, cystine, citrulline, homocysteine and lysine with systolic blood pressure and cystine with diastolic blood pressure. The differences in homocysteine levels between low- and high-sodium intakes were significantly associated with the differences in diastolic blood pressure. These associations were significant with or without considering demographic factors. Treatment with β-aminoisobutyric acid significantly attenuated high-salt-induced hypertension in Dahl salt-sensitive rats. Conclusion: These findings support the presence of new mechanisms of blood pressure regulation involving metabolic intermediaries, which could be developed as markers or therapeutic targets for salt-sensitive hypertension.
Author List
Cheng Y, Song H, Pan X, Xue H, Wan Y, Wang T, Tian Z, Hou E, Lanza IR, Liu P, Liu Y, Laud PW, Usa K, He Y, Liang MAuthors
Purushottam W. Laud PhD Professor in the Institute for Health and Equity department at Medical College of WisconsinTao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdultAmino Acids
Aminoisobutyric Acids
Animals
Biogenic Amines
Blood Pressure
Cross-Over Studies
Diet
Female
Humans
Hypertension
Male
Metabolome
Middle Aged
Rats
Rats, Inbred Dahl
Sodium Chloride, Dietary
