Urinary metabolites associated with blood pressure on a low- or high-sodium diet

Yuan Cheng, Haiying Song, Xiaoqing Pan, Hong Xue, Yifei Wan, Tao Wang, Zhongmin Tian, Entai Hou, Ian R Lanza, Pengyuan Liu, Yong Liu, Purushottam W. Laud, Kristie Usa, Yongcheng He, Mingyu Liang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 ß-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.

Original languageEnglish (US)
Pages (from-to)1468-1480
Number of pages13
JournalTheranostics
Volume8
Issue number6
DOIs
StatePublished - Jan 1 2018

Fingerprint

Sodium
Diet
Blood Pressure
Salts
Inbred Dahl Rats
Aminoisobutyric Acids
Hypertension
Cystine
Homocysteine
Citrulline
Citric Acid Cycle
Lysine
Chromatography
Linear Models
Mass Spectrometry
Arterial Pressure
Demography
Urine
Therapeutics

Keywords

  • Diet
  • Hypertension
  • Metabolomics
  • Salt

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Cheng, Y., Song, H., Pan, X., Xue, H., Wan, Y., Wang, T., ... Liang, M. (2018). Urinary metabolites associated with blood pressure on a low- or high-sodium diet. Theranostics, 8(6), 1468-1480. https://doi.org/10.7150/thno.22018

Urinary metabolites associated with blood pressure on a low- or high-sodium diet. / Cheng, Yuan; Song, Haiying; Pan, Xiaoqing; Xue, Hong; Wan, Yifei; Wang, Tao; Tian, Zhongmin; Hou, Entai; Lanza, Ian R; Liu, Pengyuan; Liu, Yong; Laud, Purushottam W.; Usa, Kristie; He, Yongcheng; Liang, Mingyu.

In: Theranostics, Vol. 8, No. 6, 01.01.2018, p. 1468-1480.

Research output: Contribution to journalArticle

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, M 2018, 'Urinary metabolites associated with blood pressure on a low- or high-sodium diet', Theranostics, vol. 8, no. 6, pp. 1468-1480. https://doi.org/10.7150/thno.22018
Cheng, Yuan ; Song, Haiying ; Pan, Xiaoqing ; Xue, Hong ; Wan, Yifei ; Wang, Tao ; Tian, Zhongmin ; Hou, Entai ; Lanza, Ian R ; Liu, Pengyuan ; Liu, Yong ; Laud, Purushottam W. ; Usa, Kristie ; He, Yongcheng ; Liang, Mingyu. / Urinary metabolites associated with blood pressure on a low- or high-sodium diet. In: Theranostics. 2018 ; Vol. 8, No. 6. pp. 1468-1480.
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abstract = "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 {\ss}-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.",
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AU - Song, Haiying

AU - Pan, Xiaoqing

AU - Xue, Hong

AU - Wan, Yifei

AU - Wang, Tao

AU - Tian, Zhongmin

AU - Hou, Entai

AU - Lanza, Ian R

AU - Liu, Pengyuan

AU - Liu, Yong

AU - Laud, Purushottam W.

AU - Usa, Kristie

AU - He, Yongcheng

AU - Liang, Mingyu

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N2 - 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 ß-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.

AB - 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 ß-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.

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KW - Metabolomics

KW - Salt

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