Regulation of Nitric Oxide Production in the Developmental Programming of Hypertension and Kidney Disease

Hsu, Chien‐Ning; Tain, You‐Lin

doi:10.3390/ijms20030681

Cited by 83 publications

(89 citation statements)

References 105 publications

(192 reference statements)

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“…Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, can be metabolized by dimethylarginine dimethylaminohydrolase to generate DMA and citrulline [38]. Noteworthily, DMA can come from the TMA−TMAO pathway as well the ADMA−NO pathway, and TMAO and ADMA both are uremic toxins related to cardiovascular risk [34,39]. Whether DMA links two pathways together to play a role in the development of hypertension in CKD awaits further elucidation.…”

Section: Discussionmentioning

confidence: 99%

Association of Trimethylamine, Trimethylamine N-oxide, and Dimethylamine with Cardiovascular Risk in Children with Chronic Kidney Disease

Hsu

Chang-Chien

Lin

et al. 2020

JCM

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Chronic kidney disease (CKD) is associated with high risk for cardiovascular disease (CVD). Gut microbiota-dependent metabolites trimethylamine (TMA), trimethylamine N-oxide (TMAO), and dimethylamine (DMA) have been linked to CKD and CVD. We examined whether these methylamines are correlated with cardiovascular risk in CKD children. A total of 115 children and adolescents with CKD stage G1–G4 were enrolled in this cross-sectional study. Children with CKD stage G2–G4 had higher plasma levels of DMA, TMA, and TMAO, but lower urinary levels of DMA and TMAO than those with CKD stage G1. Up to 53% of CKD children and adolescents had blood pressure (BP) abnormalities on 24-h ambulatory BP monitoring (ABPM). Plasma TMA and DMA levels inversely associated with high BP load as well as estimated glomerular filtration rate (eGFR). Additionally, CKD children with an abnormal ABPM profile had decreased abundance of phylum Cyanobacteria, genera Subdoligranulum, Faecalibacterium, Ruminococcus, and Akkermansia. TMA and DMA are superior to TMAO when related to high BP load and other CV risk factors in children and adolescents with early-stage CKD. Our findings highlight that gut microbiota-dependent methylamines are related to BP abnormalities and CV risk in pediatric CKD. Further studies should determine whether these microbial markers can identify children at risk for CKD progression.

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Section: Discussionmentioning

confidence: 99%

Association of Trimethylamine, Trimethylamine N-oxide, and Dimethylamine with Cardiovascular Risk in Children with Chronic Kidney Disease

Hsu

Chang-Chien

Lin

et al. 2020

JCM

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“…It is a major risk factor for kidney disease and it is the result of kidney disease [15]. Development of the kidney can be altered in response to adverse environments leading to renal programming and increased vulnerability to the development of hypertension and kidney disease in adulthood [15]. NO is a key mediator of renal physiology and blood pressure regulation.…”

Section: The Renal Systemmentioning

confidence: 99%

“…NO is a key mediator of renal physiology and blood pressure regulation. NO deficiency is a common mechanism underlying renal programming [15]. Furthermore, the kidney is an organ rich with acetylated lysines, which are found in up to >2000 unique histone and nonhistone proteins, therefore being a target of epigenetic programming [59,60].…”

Section: The Renal Systemmentioning

confidence: 99%

“…Correspondingly, several factors acting during early life have been linked to development of hypertension during adulthood but few reviews analyzing this issue have been published. Among the environmental factors that lead to hypertension preterm birth, low birth weight, gestational hypertension, maternal obesity, short-term breastfeeding, maternal smoking, low vitamin D intake and excessive postnatal weight gain may be included [15]. Living in disadvantaged neighborhoods, which implies mental stress, has also been related to the development of hypertension [16].…”

Section: Environmental Factors That May Leave Epigenetic Cues For Hypmentioning

confidence: 99%

“…Different environmental factors that may leave epigenetic cues are now well known such as pre-term birth [14], low weight at birth [1], altered programming of different organs [15] and living in disadvantageous conditions [16]. Mechanisms behind these factors include: undernutrition, oxidative stress (OS), inflammation, emotional stress, and the microbiota.…”

Section: Introductionmentioning

confidence: 99%

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Early Programming of Adult Systemic Essential Hypertension

Guarner-Lans

Ramírez-Higuera²,

Rubio-Ruiz

et al. 2020

IJMS

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Cardiovascular diseases are being included in the study of developmental origins of health and disease (DOHaD) and essential systemic hypertension has also been added to this field. Epigenetic modifications are one of the main mechanisms leading to early programming of disease. Different environmental factors occurring during critical windows in the early stages of life may leave epigenetic cues, which may be involved in the programming of hypertension when individuals reach adulthood. Such environmental factors include pre-term birth, low weight at birth, altered programming of different organs such as the blood vessels and the kidney, and living in disadvantageous conditions in the programming of hypertension. Mechanisms behind these factors that impact on the programming include undernutrition, oxidative stress, inflammation, emotional stress, and changes in the microbiota. These factors and their underlying causes acting at the vascular level will be discussed in this paper. We also explore the establishment of epigenetic cues that may lead to hypertension at the vascular level such as DNA methylation, histone modifications (methylation and acetylation), and the role of microRNAs in the endothelial cells and blood vessel smooth muscle which participate in hypertension. Since epigenetic changes are reversible, the knowledge of this type of markers could be useful in the field of prevention, diagnosis or epigenetic drugs as a therapeutic approach to hypertension.

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Maternal Garlic Oil Supplementation Prevents High‐Fat Diet‐Induced Hypertension in Adult Rat Offspring: Implications of H2S‐Generating Pathway in the Gut and Kidneys

Hsu

Hou

Chang-Chien

et al. 2021

Molecular Nutrition Food Res

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Scope Perinatal high‐fat (HF) diet induces hypertension in adult offspring. Garlic, a naturally dietary source of Hydrogen sulfide (H2S) donor, has been shown benefits in hypertension. The article examines whether maternal garlic oil supplementation can prevent hypertension induced by HF diet and elucidate its protective effects. Methods and results Pregnant rats are given either a normal diet or HF diet. Rat dams are given garlic oil or vehicle daily by oral gavage at 100 mg kg‐1 day‐1 during pregnancy and lactation. Male offspring are sacrificed at 16 weeks of age. Garlic oil supplementation during pregnancy and lactation protected against hypertension induced by HF diet in adult male offspring. The beneficial effects of garlic oil are associated with increased renal mRNA expression and activity of H2S‐generating enzymes, increased NO bioavailability, increased plasma short chain fatty acid levels, and alterations of gut microbiota composition. Garlic oil supplementation increases abundance of genus Lactobacillus, but decreases genera Turicibacter and Staphylococcus. Conclusion The data reveals associations between H2S‐generating pathway in the gut and kidneys, NO system, gut microbiota, and microbiota‐derived metabolites in hypertension induced by HF intake and provide insight to garlic oil as a hypertension reprogramming strategy for further translational research.

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Regulation of Nitric Oxide Production in the Developmental Programming of Hypertension and Kidney Disease

Cited by 83 publications

References 105 publications

Association of Trimethylamine, Trimethylamine N-oxide, and Dimethylamine with Cardiovascular Risk in Children with Chronic Kidney Disease

Association of Trimethylamine, Trimethylamine N-oxide, and Dimethylamine with Cardiovascular Risk in Children with Chronic Kidney Disease

Early Programming of Adult Systemic Essential Hypertension

Maternal Garlic Oil Supplementation Prevents High‐Fat Diet‐Induced Hypertension in Adult Rat Offspring: Implications of H2S‐Generating Pathway in the Gut and Kidneys

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