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Salt‐induced hypertension is one of the major issues worldwide and one of the main factors involved in heart and kidney failure. The objective of this study was to investigate the potential role of Benincasa hispida extracts on high salt‐induced hypertension in Dahl‐salt sensitive (D‐SS) rats and to find out the metabolic and biochemical pattern involved in the reduction of hypertension. Twenty‐six Dahl salt‐sensitive (D‐SS) rats were selected and divided into four groups. The metabolic strategy was applied to test the extracts on salt‐sensitive hypertension in kidney. Gas Chromatography–Mass spectrometry (GC–MS) was used to identify the potent biochemical profile in renal medulla and cortex of rat kidneys. The differential metabolites of cortex and medulla, enrichment analysis and pathway analysis were performed using metabolomics data. The GC–MS data revealed that 24 different antihypertensive metabolites was detected in renal cortex, while 16 were detected in renal medulla between different groups. The significantly metabolic pathways namely citrate cycle, glutathione metabolism, glycine, serine, and threonine metabolism, glyoxylate and dicarboxylate metabolism, glycerolipid metabolism, alanine, aspartate and glutamate metabolism in renal cortex and glycerolipid metabolism, pentose phosphate pathway, citrate cycle, glycolysis, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis in renal medulla were involved in the process of Hypertension. The results suggest that the extract mainly alter the metabolic pathways of amino acid in Dahl salt‐sensitive rats and its antioxidant potential reduced the hypertension patterns of Salt‐sensitive rat. The antihypertensive components malic acid, aspartic acid, and glycine of extract can be used as therapeutic drugs to protect kidneys from salt‐induced hypertension. Practical applications: Hypertension is a multifactorial disease and one of the risk factors for heart and kidney failure. Benincasa hispida is a widely used vegetable in China, which belongs to the Cucurbitaceae family. Benincasa hispida (wax gourd) has been used in traditional Chinese medicine for the treatment of inflammation and hypertension. The Benincasa hispida contains many compounds such as amino acids, carbohydrates, volatile compounds, vitamins, and minerals. The amino acid present in the pulp of Benincasa hispida are ornithine, threonine, aspartate, glutamate, serine, glycine, proline, alanine, valine, cysteine, isoleucine, tyrosine, leucine, lysine, phenylalanine, histidine, arginine, and γ‐aminobutyric acid. Our results showed that Benincasa hispida is one of the potent natural antioxidants and can maintain normal blood pressure in Dahl salt‐sensitive rats (D‐SS). In conclusion, the current results provide good theoretical basis for the development and research using Benincasa hispida as an effective natural antioxidant for hypertension. [ABSTRACT FROM AUTHOR]

The human Dietary Approaches to Stop Hypertension-Sodium Trial has shown that β-aminoisobutyric acid (BAIBA) may prevent the development of salt-sensitive hypertension (SSHT). However, the specific antihypertensive mechanism remains unclear in the renal tissues of salt-sensitive (SS) rats. In this study, BAIBA (100 mg/kg/day) significantly attenuated SSHT via increased nitric oxide (NO) content in the renal medulla, and it induced a significant increase in NO synthesis substrates (l-arginine and malic acid) in the renal medulla. BAIBA enhanced the activity levels of total NO synthase (NOS), inducible NOS, and constitutive NOS. BAIBA resulted in increased fumarase activity and decreased fumaric acid content in the renal medulla. The high-salt diet (HSD) decreased fumarase expression in the renal cortex, and BAIBA increased fumarase expression in the renal medulla and renal cortex. Furthermore, in the renal medulla, BAIBA increased the levels of ATP, ADP, AMP, and ADP/ATP ratio, thus further activating AMPK phosphorylation. BAIBA prevented the decrease in renal medullary antioxidative defenses induced by the HSD. In conclusion, BAIBA's antihypertensive effect was underlined by the phosphorylation of AMPK, the prevention of fumarase's activity reduction caused by the HSD, and the enhancement of NO content, which in concert attenuated SSHT in SS rats. [ABSTRACT FROM AUTHOR]