Early Supplementation of <scp>d</scp>‐Cysteine or <scp>l</scp>‐Cysteine Prevents Hypertension and Kidney Damage in Spontaneously Hypertensive Rats Exposed to High‐Salt Intake

Hsu, Chien‐Ning; Lin, Yu‐Ju; Lu, Pei-Chen; Tain, You‐Lin

doi:10.1002/mnfr.201700596

Cited by 33 publications

(36 citation statements)

References 31 publications

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“…In line with previous studies [14,16,38,39], our report supports the notion that H 2 S-generating system is involved in the development of hypertension in SHRs. In the current study, mother SHRs treated with NAC, the precursor of H 2 S, in pregnancy and lactation can increase renal H 2 S-generating activity and protein levels and prevent hypertension in their male adult offspring.…”

Section: Discussionsupporting

confidence: 93%

“…L-cysteine is the major precursor for endogenous H 2 S synthesis [12]. Our previous study reported that early supplementation of L-cysteine in the prehypertensive stage can protect SHRs against high-salt-enhanced elevation of BP and kidney injury [16]. N-acetylcysteine (NAC), which is a stable analogue of L-cysteine, is currently mainly used as an antioxidant [17].…”

Section: Introductionmentioning

confidence: 99%

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Maternal N-Acetylcysteine Therapy Prevents Hypertension in Spontaneously Hypertensive Rat Offspring: Implications of Hydrogen Sulfide-Generating Pathway and Gut Microbiota

et al. 2020

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Hypertension can come from early life. N-acetylcysteine (NAC), a hydrogen sulfide (H2S) precursor as well as an antioxidant, has antihypertensive effect. We investigated whether maternal NAC therapy can protect spontaneously hypertensive rats (SHR) male offspring against hypertension. The pregnant rats were assigned to four groups: SHRs without treatment; Wistar Kyoto (WKY) without treatment; SHR+NAC, SHRs received 1% NAC in drinking water throughout pregnancy and lactation; and, WKY+NAC, WKY rats received 1% NAC in drinking water during pregnancy and lactation. Male offspring (n = 8/group) were killed at 12 weeks of age. Maternal NAC therapy prevented the rise in systolic blood pressure (BP) in male SHR offspring at 12 weeks of age. Renal cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulphurtransferase (3MST) protein levels and H2S-releasing activity were increased in the SHR+NAC offspring. Maternal NAC therapy increased fecal H2S and thiosulfate levels in the SHR+NAC group. Additionally, maternal NAC therapy differentially shaped gut microbiota and caused a distinct enterotype in each group. The protective effect of maternal NAC therapy against hypertension in SHR offspring is related to increased phylum Actinobacteria and genera Bifidobacterium and Allobaculum, but decreased phylum Verrucomicrobia, genera Turicibacter, and Akkermansia. Several microbes were identified as microbial markers, including genera Bifidobacterium, Allobaculum, Holdemania, and Turicibacter. Our results indicated that antioxidant therapy by NAC in pregnant SHRs can prevent the developmental programming of hypertension in male adult offspring. Our findings highlight the interrelationships among H2S-generating pathway in the kidneys and gut, gut microbiota, and hypertension. The implications of maternal NAC therapy elicited long-term protective effects on hypertension in later life that still await further clinical translation.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Maternal N-Acetylcysteine Therapy Prevents Hypertension in Spontaneously Hypertensive Rat Offspring: Implications of Hydrogen Sulfide-Generating Pathway and Gut Microbiota

et al. 2020

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“…demonstrated that the high polyphenol concentrations in lingonberry juice exerted anti‐inflammatory effects in a rat model of salt‐induced hypertension. Hsu et al . reported that early supplementation of d ‐ or l ‐cysteine prevented hypertension and kidney damage in HSD‐fed rats.…”

Section: Discussionmentioning

confidence: 99%

Targeting the Gut Microbiota to Investigate the Mechanism of Lactulose in Negating the Effects of a High‐Salt Diet on Hypertension

Zheng

Zhao

Tian

et al. 2019

Molecular Nutrition Food Res

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Scope: High-salt diets (HSDs) are widely considered to cause health problems such as gut microecological imbalances, constipation, and hypertension. This study explores how lactulose as a safe molecule can stimulate bodily responses to alleviate salt-sensitive hypertension by regulating the gut microbiotas of HSD-fed mice. Methods and results: After 4 weeks, the blood pressures of mice fed a high-salt plus lactulose diet (HSLD) are significantly lower than those of the HSD-fed mice. The HSD increases the abundances of Alistipes and Ruminococcaceae UCG 009 and reduced the abundance of Lactobacillus in the gut, while lactulose supplementation increases the abundances of Bifidobacterium, Alloprevotella, and Subdoligranulum. Fecal metabolic profiling shows significant increases in metabolites involved in ATP-binding cassette transporter pathways, and tryptophan metabolism is significantly reduced in the HSLD group compared with the HSD group. Lactulose maintains the intestinal microenvironmental health in the HSD-fed mice by improving glycolipid metabolism, decreasing the small intestinal interleukin-17a (IL-17a) and interleukin-22 (IL-22) mRNA levels and serum IL-17a and IL-22 levels, relieving constipation, increasing fecal sodium, and reducing intestinal permeability. Conclusion: Lactulose negates salt-sensitive hypertension. Regulating the gut microbiota is a potential treatment for salt-sensitive hypertension.

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“…Of note, pharmacotherapies will be narrowly restricted to key periods during early development. These H 2 S treatment modalities are listed in Table 1 [ 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. This list is by no means complete and is expected to grow rapidly as the field of DOHaD research flourishes.…”

Section: Reprogramming Strategy Targeting the H 2 mentioning

confidence: 99%

“…So far, very few studies have addressed DOHaD research to explore the protective role of H 2 S precursors in the kidney in response to a variety of early-life insults. We first showed that early supplementation of d - or l -cysteine between 4 and 6 weeks of age (i.e., prehypertensive stage) can protect SHRs against high-salt-enhanced elevation of BP and kidney injury [ 62 ]. Although a previous report has shown that the d -cysteine pathway is 80-fold greater in H 2 S-producing activity in the kidney compared to the l -cysteine pathway [ 71 ], our data revealed that the protective effects on BP are similar.…”

Section: Reprogramming Strategy Targeting the H 2 mentioning

confidence: 99%

Hydrogen Sulfide in Hypertension and Kidney Disease of Developmental Origins

Hsu

Tain

2018

IJMS

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Adverse environments occurring during kidney development may produce long-term programming effects, namely renal programming, to create increased vulnerability to the development of later-life hypertension and kidney disease. Conversely, reprogramming is a strategy aimed at reversing the programming processes in early life, even before the onset of clinical symptoms, which may counter the rising epidemic of hypertension and kidney disease. Hydrogen sulfide (H2S), the third gasotransmitter, plays a key role in blood pressure regulation and renal physiology. This review will first present the role of H2S in the renal system and provide evidence for the links between H2S signaling and the underlying mechanisms of renal programming, including the renin–angiotensin system, oxidative stress, nutrient-sensing signals, sodium transporters, and epigenetic regulation. This will be followed by potential H2S treatment modalities that may serve as reprogramming strategies to prevent hypertension and kidney disease of developmental origins. These H2S treatment modalities include precursors for H2S synthesis, H2S donors, and natural plant-derived compounds. Despite emerging evidence from experimental studies in support of reprogramming strategies targeting the H2S signaling pathway to protect against hypertension and kidney disease of developmental origins, these results need further clinical translation.

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Early Supplementation of d‐Cysteine or l‐Cysteine Prevents Hypertension and Kidney Damage in Spontaneously Hypertensive Rats Exposed to High‐Salt Intake

Abstract: Early supplementation of d- or l-cysteine before hypertension becomes evident and may protect against hypertension and kidney damage in adult SHRs exposed to high salt consumption via regulation of oxidative stress, renin-angiotensin system, and H S-generating pathways.

Cited by 33 publications

References 31 publications

Maternal N-Acetylcysteine Therapy Prevents Hypertension in Spontaneously Hypertensive Rat Offspring: Implications of Hydrogen Sulfide-Generating Pathway and Gut Microbiota

Maternal N-Acetylcysteine Therapy Prevents Hypertension in Spontaneously Hypertensive Rat Offspring: Implications of Hydrogen Sulfide-Generating Pathway and Gut Microbiota

Targeting the Gut Microbiota to Investigate the Mechanism of Lactulose in Negating the Effects of a High‐Salt Diet on Hypertension

Hydrogen Sulfide in Hypertension and Kidney Disease of Developmental Origins

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