L-phenylalanine attenuates high salt-induced hypertension in Dahl SS rats through activation of GCH1-BH4.

Zhengjun Wang,Chen Cheng,Chen Zhang,Xiaoyu Yang,Michael Bader

doi:10.1371/journal.pone.0250126

Zhengjun Wang, Chen Cheng + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0250126

Copy DOI

Abstract

Amino acid metabolism plays an important role in controlling blood pressure by regulating the production of NO and ROS. The present study examined amino acid levels in the serum of Dahl SS rats and SS.13BN rats fed a low or high salt diet. We observed that 8 of 27 amino acids responded to a high salt diet in SS rats. Thus, we hypothesized that a defect in amino acids may contribute to the development of salt-induced hypertension. L-phenylalanine was used to treat SS rats with a low or high salt diet. The results demonstrated that L-phenylalanine supplementation significantly enhanced the serum nitrite levels and attenuated the high salt-induced hypertension in SS rats. Low levels of BH4 and nitrite and the impaired vascular response to acetylcholine were rescued by L-phenylalanine supplementation. Moreover, increased GTP cyclohydrolase (GCH1) mRNA, levels of BH4 and nitrite, and reduced superoxide production were observed in the kidneys of hypertensive SS rats with L-phenylalanine. The antihypertensive effects of L-phenylalanine might be mediated by enhancing BH4 biosynthesis and decreasing superoxide production from NO synthase, thereby protecting vascular and kidney function with reduced ROS and elevated NO levels. The present study demonstrated that L-phenylalanine supplementation restored vascular function, suggesting L-phenylalanine represented a potential target to attenuate high salt-sensitive hypertension through GCH1-BH4.

Highlights

High salt-induced hypertension and cardiovascular diseases are important risk factors for death worldwide [1, 2]
A higher intake of branched chain amino acid (BCAA), valine, was associated with a higher risk of incident hypertension [12]. These results strongly suggest that the amino acid composition in the diet is closely related to control of blood pressure [13]
We hypothesize that amino acids metabolism may contribute to high salt induce hypertension and the aim of this study was to characterize the metabolic profiles of amino acids in SS rats. We evaluated whether these amino acids, especially L-phenylalanine, which is known to increase GCH activity and BH4 biosynthesis, would attenuate the increased blood pressure in high salt-induced Dahl SS rats

Summary

Introduction

High salt-induced hypertension and cardiovascular diseases are important risk factors for death worldwide [1, 2]. Restricted salt intake is known to be beneficial, excessive salt intake still persists in some areas, especially in North China [3]. Dahl salt-sensitive (SS) rats are widely used for the study of hypertension and show the phenotype similar to human salt-sensitive hypertension [4]. L-phenylalanine attenuates hypertension through GCH1-BH4 and analysis, decision to publish, or preparation of the manuscript

Objectives

Methods

Results

Conclusion