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

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 856 ◽  
Author(s):  
Chien-Ning Hsu ◽  
Chih-Yao Hou ◽  
Guo-Ping Chang-Chien ◽  
Sufan Lin ◽  
You-Lin Tain
Keyword(s):  
Drinking Water ◽  
Hydrogen Sulfide ◽  
Gut Microbiota ◽  
Spontaneously Hypertensive Rat ◽  
Later Life ◽  
Male Offspring ◽  
Protective Effects ◽  
Male Adult ◽  
Spontaneously Hypertensive ◽  
Pregnancy And Lactation

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.

scholarly journals Lactiplantibacillus plantarum WJL administration during pregnancy and lactation improves lipid profile, insulin sensitivity and gut microbiota diversity in dyslipidemic dams and protects male offspring against cardiovascular dysfunction in later life

2020 ◽  
Vol 11 (10) ◽  
pp. 8939-8950
Author(s):  
Keyth Sulamitta de Lima Guimarães ◽  
Valdir de Andrade Braga ◽  
Sylvana I. S. Rendeiro de Noronha ◽  
Whyara Karoline Almeida da Costa ◽  
Kassem Makki ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Gut Microbiota ◽  
Lipid Profile ◽  
Later Life ◽  
Male Offspring ◽  
Cardiovascular Dysfunction ◽  
Pregnancy And Lactation ◽  
Microbiota Diversity

Lactiplantibacillus plantarum WJL administration during pregnancy and lactation improves gut microbiota diversity.

scholarly journals Maternal Administration of Probiotic or Prebiotic Prevents Male Adult Rat Offspring against Developmental Programming of Hypertension Induced by High Fructose Consumption in Pregnancy and Lactation

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1229 ◽  
Author(s):  
Chien-Ning Hsu ◽  
Yu-Ju Lin ◽  
Chih-Yao Hou ◽  
You-Lin Tain
Keyword(s):  
Gut Microbiota ◽  
Targeted Therapies ◽  
Lactobacillus Casei ◽  
Developmental Programming ◽  
Nutrient Sensing ◽  
Male Offspring ◽  
Male Adult ◽  
High Fructose ◽  
Probiotic Lactobacillus ◽  
Pregnancy And Lactation

Excessive intake of fructose is associated with hypertension. Gut microbiota and their metabolites are thought to be associated with the development of hypertension. We examined whether maternal high-fructose (HF) diet-induced programmed hypertension via altering gut microbiota, regulating short-chain fatty acids (SCFAs) and their receptors, and mediating nutrient-sensing signals in adult male offspring. Next, we aimed to determine whether early gut microbiota-targeted therapies with probiotic Lactobacillus casei and prebiotic inulin can prevent maternal HF-induced programmed hypertension. Pregnant rats received 60% high-fructose (HF) diet, with 2 × 108 CFU/day Lactobacillus casei via oral gavage (HF+Probiotic), or with 5% w/w long chain inulin (HF+prebiotic) during pregnancy and lactation. Male offspring (n = 7–8/group) were assigned to four groups: control, HF, HF+Probiotic, and HF+Prebiotic. Rats were sacrificed at 12 weeks of age. Maternal probiotic Lactobacillus casei and prebiotic inulin therapies protect against hypertension in male adult offspring born to fructose-fed mothers. Probiotic treatment prevents HF-induced hypertension is associated with reduced plasma acetate level and decreased renal mRNA expression of Olfr78. While prebiotic treatment increased plasma propionate level and restored HF-induced reduction of Frar2 expression. Maternal HF diet has long-term programming effects on the adult offspring’s gut microbiota. Probiotic and prebiotic therapies exerted similar protective effects on blood pressure but they showed different mechanisms on modulation of gut microbiota. Maternal HF diet induced developmental programming of hypertension, which probiotic Lactobacillus casei or prebiotic inulin therapy prevented. Maternal gut microbiota-targeted therapies could be reprogramming strategies to prevent the development of hypertension caused by maternal consumption of fructose-rich diet.

scholarly journals Altered Gut Microbiota and Its Metabolites in Hypertension of Developmental Origins: Exploring Differences between Fructose and Antibiotics Exposure

2021 ◽  
Vol 22 (5) ◽  
pp. 2674
Author(s):  
Chien-Ning Hsu ◽  
Julie Y. H. Chan ◽  
Kay L. H. Wu ◽  
Hong-Ren Yu ◽  
Wei-Chia Lee ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Negative Impact ◽  
Short Chain Fatty Acids ◽  
Normal Diet ◽  
Male Offspring ◽  
Sprague Dawley ◽  
Minocycline Treatment ◽  
High Fructose ◽  
Induced Hypertension ◽  
Pregnancy And Lactation

Gut microbiota-derived metabolites, in particular short chain fatty acids (SCFAs) and their receptors, are linked to hypertension. Fructose and antibiotics are commonly used worldwide, and they have a negative impact on the gut microbiota. Our previous study revealed that maternal high-fructose (HF) diet-induced hypertension in adult offspring is relevant to altered gut microbiome and its metabolites. We, therefore, intended to examine whether minocycline administration during pregnancy and lactation may further affect blood pressure (BP) programmed by maternal HF intake via mediating gut microbiota and SCFAs. Pregnant Sprague-Dawley rats received a normal diet or diet containing 60% fructose throughout pregnancy and lactation periods. Additionally, pregnant dams received minocycline (50 mg/kg/day) via oral gavage or a vehicle during pregnancy and lactation periods. Four groups of male offspring were studied (n = 8 per group): normal diet (ND), high-fructose diet (HF), normal diet + minocycline (NDM), and HF + minocycline (HFM). Male offspring were killed at 12 weeks of age. We observed that the HF diet and minocycline administration, both individually and together, causes the elevation of BP in adult male offspring, while there is no synergistic effect between them. Four groups displayed distinct enterotypes. Minocycline treatment leads to an increase in the F/B ratio, but decreased abundance of genera Lactobacillus, Ruminococcus, and Odoribacter. Additionally, minocycline treatment decreases plasma acetic acid and butyric acid levels. Hypertension programmed by maternal HF diet plus minocycline exposure is related to the increased expression of several SCFA receptors. Moreover, minocycline- and HF-induced hypertension, individually or together, is associated with the aberrant activation of the renin–angiotensin system (RAS). Conclusively, our results provide a new insight into the support of gut microbiota and its metabolite SCAFs in the developmental programming of hypertension and cast new light on the role of RAS in this process, which will help prevent hypertension programmed by maternal high-fructose and antibiotic exposure.

scholarly journals Maternal Melatonin Therapy Attenuates Methyl-Donor Diet-Induced Programmed Hypertension in Male Adult Rat Offspring

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1407 ◽  
Author(s):  
You-Lin Tain ◽  
Julie Chan ◽  
Chien-Te Lee ◽  
Chien-Ning Hsu
Keyword(s):  
Methylation Status ◽  
Normal Diet ◽  
Male Offspring ◽  
Adult Offspring ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Deficient Diet ◽  
Male Adult ◽  
Methyl Donor ◽  
Adult Rat

Although pregnant women are advised to consume methyl-donor food, some reports suggest an adverse outcome. We investigated whether maternal melatonin therapy can prevent hypertension induced by a high methyl-donor diet. Female Sprague-Dawley rats received either a normal diet, a methyl-deficient diet (L-MD), or a high methyl-donor diet (H-MD) during gestation and lactation. Male offspring were assigned to four groups (n = 7–8/group): control, L-MD, H-MD, and H-MD rats were given melatonin (100 mg/L) with their drinking water throughout the period of pregnancy and lactation (H-MD+M). At 12 weeks of age, male offspring exposed to a L-MD or a H-MD diet developed programmed hypertension. Maternal melatonin therapy attenuated high methyl-donor diet-induced programmed hypertension. A maternal L-MD diet and H-MD diet caused respectively 938 and 806 renal transcripts to be modified in adult offspring. The protective effects of melatonin against programmed hypertension relate to reduced oxidative stress, increased urinary NO2− level, and reduced renal expression of sodium transporters. A H-MD or L-MD diet may upset the balance of methylation status, leading to alterations of renal transcriptome and programmed hypertension. A better understanding of reprogramming effects of melatonin might aid in developing a therapeutic strategy for the prevention of hypertension in adult offspring exposed to an excessive maternal methyl-supplemented diet.

scholarly journals Resveratrol Butyrate Esters Inhibit BPA-Induced Liver Damage in Male Offspring Rats by Modulating Antioxidant Capacity and Gut Microbiota

2021 ◽  
Vol 22 (10) ◽  
pp. 5273
Author(s):  
Jin-Xian Liao ◽  
Yu-Wei Chen ◽  
Ming-Kuei Shih ◽  
You-Lin Tain ◽  
Yao-Tsung Yeh ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Antioxidant Capacity ◽  
Liver Damage ◽  
Short Chain Fatty Acids ◽  
Extramedullary Hematopoiesis ◽  
Male Offspring ◽  
Female Rats ◽  
Protective Effects ◽  
Mononuclear Cell Infiltration ◽  
Metabolic Disruption

Resveratrol can affect the physiology or biochemistry of offspring in the maternal–fetal animal model. However, it exhibits low bioavailability in humans and animals. Fifteen-week SD pregnant female rats were orally administered bisphenol A (BPA) and/or resveratrol butyrate ester (RBE), and the male offspring rats (n = 4–8 per group) were evaluated. The results show that RBE treatment (BPA + R30) compared with the BPA group can reduce the damage caused by BPA (p < 0.05). RBE enhanced the expression of selected genes and induced extramedullary hematopoiesis and mononuclear cell infiltration. RBE increased the abundance of S24-7 and Adlercreutzia in the intestines of the male offspring rats, as well as the concentrations of short-chain fatty acids (SCFAs) in the feces. RBE also increased the antioxidant capacity of the liver by inducing Nrf2, promoting the expression of HO-1, SOD, and CAT. It also increased the concentration of intestinal SCFAs, enhancing the barrier formed by intestinal cells, thereby preventing BPA-induced metabolic disruption in the male offspring rats, and reduced liver inflammation. This study identified a potential mechanism underlying the protective effects of RBE against the liver damage caused by BPA exposure during the peri-pregnancy period, and the influence of the gut microbiota on the gut–liver axis in the offspring.

scholarly journals Gut Microbiota Profile Identifies Transition From Compensated Cardiac Hypertrophy to Heart Failure in Hypertensive Rats

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1545-1554
Author(s):  
Elena Gutiérrez-Calabrés ◽  
Adriana Ortega-Hernández ◽  
Javier Modrego ◽  
Rubén Gómez-Gordo ◽  
Alicia Caro-Vadillo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Gut Microbiota ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Metabolic Functions ◽  
Hypertensive Rat ◽  
Spontaneously Hypertensive Heart Failure ◽  
Wistar Kyoto ◽  
And Function ◽  
Gut Microbial Community

Microcirculatory alterations displayed by patients with heart failure (HF) induce structural and functional intestinal changes that may affect normal gut microbial community. At the same time, gut microbiota can influence pathological mechanisms implicated in HF progression. However, it is unknown whether gut microbiota dysbiosis can precede the development of cardiac alterations in HF or it is only a mere consequence. Our aim was to investigate the potential relationship between gut microbiota composition and HF development by comparing spontaneously hypertensive heart failure and spontaneously hypertensive rat models. Gut microbiota from spontaneously hypertensive heart failure, spontaneously hypertensive rat, and normotensive Wistar Kyoto rats at 9 and 19 months of age was analyzed by sequencing the 16S ribosomal RNA gene, and KEGG metabolic pathways associated to 16S profiles were predicted. Beta diversity, Firmicutes / Bacteroidetes ratio, taxonomic abundances, and potential metabolic functions of gut microbiota were significantly different in spontaneously hypertensive heart failure with respect to spontaneously hypertensive rat before (9 months) and after (19 months) cardiac differences were presented. Nine-month-old spontaneously hypertensive heart failure showed a significant increase in the genera Paraprevotella, Oscillospira, Prevotella 9, Faecalitalea, Faecalibacterium, Ruminiclostridium 6, Phascolarctobacterium, Butyrivibrio, Parasutterella, and Parabacteroides compared with both Wistar Kyoto and spontaneously hypertensive rat, while Ruminiclostridium 9 , Oscillibacter , Ruminiclostridium , Mucispirillum, Intestinimonas , and Akkermansia were diminished. Of them, Akkermansia, Prevotella 9 , Paraprevotella , and Phascolarctobaterium were associated to changes in cardiac structure and function. Our results demonstrate an association between specific changes in gut microbiota and the development of HF in a hypertensive model of HF and further support the intervention to restore gut microbiota as an innovative therapeutic strategy for preventing HF.

scholarly journals Potassium Alginate Oligosaccharides Alter Gut Microbiota, and Have Potential to Prevent the Development of Hypertension and Heart Failure in Spontaneously Hypertensive Rats

2021 ◽  
Vol 22 (18) ◽  
pp. 9823
Author(s):  
Zhen-Lian Han ◽  
Meng Chen ◽  
Xiao-Dan Fu ◽  
Min Yang ◽  
Maria Hrmova ◽  
...  
Keyword(s):  
Heart Failure ◽  
Gut Microbiota ◽  
Natriuretic Peptide ◽  
Spontaneously Hypertensive Rats ◽  
Therapeutic Potential ◽  
Favorable Effect ◽  
Protective Effects ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Alginate Oligosaccharides

Food-derived oligosaccharides show promising therapeutic potential in lowering blood pressure (BP), but the mechanism is poorly understood. Recently, the potential role of gut microbiota (GM) in hypertension has been investigated, but the specific GM signature that may participate in hypertension remains unclear. To test the potassium alginate oligosaccharides (PAO) mechanism in lowering BP and specific microbial signature changes in altering GM, we administered various dosages of PAO in 40 spontaneously hypertensive rats for a duration of six weeks. We analyzed BP, sequenced the 16S ribosomal DNA gene in the cecum content, and gathered RNA-seq data in cardiac tissues. We showed that the oral administration of PAO could significantly decrease systolic BP and mean arterial pressure. Transcriptome analyses demonstrated that the protective effects of developing heart failure were accompanied by down-regulating of the Natriuretic Peptide A gene expression and by decreasing the concentrations of angiotensin II and atrial natriuretic peptide in plasma. In comparison to the Vehicle control, PAO could increase the microbial diversity by altering the composition of GM. PAO could also decrease the ratio of Firmicutes to Bacteroidetes by decreasing the abundance of Prevotella and Phascolarctobacterium bacteria. The favorable effect of PAO may be added to the positive influence of the abundance of major metabolites produced by Gram-negative bacteria in GM. We suggest that PAO caused changes in GM, and thus, they played an important role in preventing the development of cardiovascular disease.

scholarly journals Water deprivation-partial rehydration induces sensitization of sodium appetite and alteration of hypothalamic transcripts

2016 ◽  
Vol 310 (1) ◽  
pp. R15-R23 ◽  
Author(s):  
Daniela T. B. Pereira-Derderian ◽  
Regina C. Vendramini ◽  
José V. Menani ◽  
Silvana Chiavegatto ◽  
Laurival A. De Luca
Keyword(s):  
Water Deprivation ◽  
Behavioral Plasticity ◽  
Spontaneously Hypertensive Rat ◽  
Sodium Intake ◽  
Renin Angiotensin System ◽  
Male Adult ◽  
Spontaneously Hypertensive ◽  
Sodium Appetite ◽  
Wistar Kyoto ◽  
The Brain

iSodium intake occurs either as a spontaneous or induced behavior, which is enhanced, i.e., sensitized, by repeated episodes of water deprivation followed by subsequent partial rehydration (WD-PR). In the present work, we examined whether repeated WD-PR alters hypothalamic transcripts related to the brain renin-angiotensin system (RAS) and apelin system in male normotensive Holtzman rats (HTZ). We also examined whether the sodium intake of a strain with genetically inherited high expression of the brain RAS, the spontaneously hypertensive rat (SHR), responds differently than HTZ to repeated WD-PR. We found that repeated WD-PR, besides enhancing spontaneous and induced 0.3 M NaCl intake, increased the hypothalamic expression of angiotensinogen, aminopeptidase N, and apelin receptor transcripts (43%, 60%, and 159%, respectively) in HTZ at the end of the third WD-PR. Repeated WD-PR did not change the daily spontaneous 0.3 M NaCl intake and barely changed the need-induced 0.3 M NaCl intake of SHR. The same treatment consistently enhanced spontaneous daily 0.3 M NaCl intake in the normotensive Wistar-Kyoto rats. The results show that repeated WD-PR produces alterations in hypothalamic transcripts and also sensitizes sodium appetite in HTZ. They suggest an association between the components of hypothalamic RAS and the apelin system, with neural and behavioral plasticity produced by repeated episodes of WD-PR in a normotensive strain. The results also indicate that the inherited hyperactive brain RAS is not a guarantee for sensitization of sodium intake in the male adult SHR exposed to repeated WD-PR.

Abstract P171: Gut Microbiota-Derived Hydrogen Sulfide is Reduced in Spontaneously Hypertensive Rats

Hypertension ◽  
2019 ◽  
Vol 74 (Suppl_1) ◽  
Author(s):  
Basak Donertas ◽  
Wendi L. Malphurs ◽  
David M. Baekey ◽  
David Julian ◽  
Jasenka Zubcevic
Keyword(s):  
Hydrogen Sulfide ◽  
Gut Microbiota ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

scholarly journals Maternal Treatment With Captopril Persistently Alters Gut-Brain Communication and Attenuates Hypertension of Male Offspring

Hypertension ◽  
2020 ◽  
Vol 75 (5) ◽  
pp. 1315-1324 ◽  
Author(s):  
Hong-Bao Li ◽  
Tao Yang ◽  
Elaine M. Richards ◽  
Carl J. Pepine ◽  
Mohan K. Raizada
Keyword(s):  
Blood Pressure ◽  
Enzyme Inhibitor ◽  
Spontaneously Hypertensive Rat ◽  
Current Knowledge ◽  
Antibacterial Properties ◽  
Male Offspring ◽  
Sterile Water ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Wistar Kyoto

Maternal-fetal crosstalk has been implicated in long-term control of the health of offspring, including transgenerational hypertension. However, current knowledge is limited regarding maternal influences on the gut and its microbiome in blood pressure control in offspring. Therefore, the current study was designed to test the hypothesis that maternal factors influence the gut-brain axis impacting hypertension in offspring. We elected to use captopril, an antihypertensive angiotensin-converting enzyme inhibitor that possesses antibacterial properties, for the study. Pregnant female spontaneously hypertensive rats and normotensive Wistar Kyoto rats were treated with captopril water (100 mg/[kg·day]) or sterile water throughout pregnancy and lactation. At weaning, the pups from dams drinking sterile water were continued with sterile water until 12 weeks of age. The male pups from dams drinking captopril water were divided at weaning into 2 groups: offspring drinking captopril water and offspring withdrawn from captopril water, then drinking sterile water until 12 weeks of age. Captopril changed gut microbiota of spontaneously hypertensive rat dams, and some of these changes were reflected in their 12-week-old male offspring. These 12-week-old spontaneously hypertensive rat male offspring exposed to captopril via dams demonstrated persistently decreased systolic blood pressure, decreased number of activated microglia and neuroinflammation, as well as improvement of gut inflammation and permeability. Therefore, maternal captopril treatment improves the dysregulated gut-brain axis in spontaneously hypertensive rat male offspring, providing conceptual support that targeting the gut-brain axis via the mother may be a viable strategy for control of hypertension in the offspring.

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