scholarly journals Changes in Gut Microbiota Induced by Doxycycline Influence in Vascular Function and Development of Hypertension in DOCA-Salt Rats

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2971
Author(s):  
Iñaki Robles-Vera ◽  
Néstor de la Visitación ◽  
Marta Toral ◽  
Manuel Sánchez ◽  
Miguel Romero ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Gut Microbiota ◽  
Vascular Function ◽  
Bacterial Population ◽  
Cardiovascular Pathology ◽  
Male Wistar Rats ◽  
Lactate Levels ◽  
Independent Model ◽  
Microbial Effects

Previous experiments in animals and humans show that shifts in microbiota and its metabolites are linked to hypertension. The present study investigates whether doxycycline (DOX, a broad-spectrum tetracycline antibiotic) improves dysbiosis, prevent cardiovascular pathology and attenuate hypertension in deoxycorticosterone acetate (DOCA)-salt rats, a renin-independent model of hypertension. Male Wistar rats were randomly assigned to three groups: control, DOCA-salt hypertensive rats, DOCA-salt treated with DOX for 4 weeks. DOX decreased systolic blood pressure, improving endothelial dysfunction and reducing aortic oxidative stress and inflammation. DOX decreased lactate-producing bacterial population and plasma lactate levels, improved gut barrier integrity, normalized endotoxemia, plasma noradrenaline levels and restored the Treg content in aorta. These data demonstrate that DOX through direct effects on gut microbiota and its non-microbial effects (anti-inflammatory and immunomodulatory) reduces endothelial dysfunction and the increase in blood pressure in this low-renin form of hypertension.

scholarly journals The effect of Sang-qi Granules on blood pressure and endothelial dysfunction in stageI or II hypertension: study protocol for a randomized double-blind double-simulation controlled trial

2019 ◽  
Author(s):  
Haoyue Shi ◽  
Deshuang Yang ◽  
Jiajun Qiao ◽  
Rui Sun ◽  
Ruihan Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Short Form ◽  
Controlled Trial ◽  
Ankle Brachial Index ◽  
Vascular Endothelial ◽  
Double Blind ◽  
Endothelial Cell Function ◽  
Self Rating

Abstract Background Hypertension is an important worldwide public health challenge because of its high prevalence and concomitant risks of cardiovascular disease. It induces half of the coronary heart disease and approximately two-thirds of the cerebrovascular disease burdens. Vascular endothelial dysfunction plays important roles in the pathophysiology of essential hypertension. Sang-qi Granules (SQG), a Chinese herbal formula, is used to treat I or II hypertension. Several animal experimental studies have shown that SQG can lower blood pressure and myocardial fibrosis by suppressing inflammatory responses. However, there is no standard clinical trial to confirm this and whether SQG can improve endothelial cell function is unknown.Methods In this randomized, double-blind, double-simulation controlled trial, 300 patients with stage I or II hypertension will be recruited and randomly allocated in a 1:1:1 ratio to group A(treatment with SQG and placebo of Cozaar), group B (treatment with Cozaar and placebo of SQG), and group C (treatment with SQG and Cozaar). SQG (or its placebo) will be administrated twice a day at the doze of 10g each time, and 50mg Cozaar(or its placebo) will be administrated once in the morning. The primary endpoint is the drug efficiency of the each three groups. The secondary endpoints are the change of average systolic and diastolic blood pressure during the day and the night, the change of blood pressure drop rate at night, target organ damage assessment (heart rate variability, ankle-brachial index and pulse wave velocity), symptoms improvement assessment (hypertension symptom scale, TCM syndrome integral scale, Pittsburgh sleep quality index scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale and the Short Form-36 Health Survey), blood lipids, serum indicators of vascular function (changes in serum ET-1, TXA2, NO, PGI2 values) and safety indicators.Discussion This study will provide clinical evidence for the efficacy and safety of SQG in the treatment of hypertension. Meanwhile, the possible mechanism of SQG for lowering blood pressure will be further explored by observing the protective effect of SQG on vascular endothelial function, as well as its effect on related clinical symptoms, risk factors and target organs of hypertension.

scholarly journals Sleep fragmentation increases blood pressure and is associated with alterations in the gut microbiome and fecal metabolome in rats

2020 ◽  
Vol 52 (7) ◽  
pp. 280-292 ◽  
Author(s):  
Katherine A. Maki ◽  
Larisa A. Burke ◽  
Michael W. Calik ◽  
Miki Watanabe-Chailland ◽  
Dagmar Sweeney ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Gut Microbiota ◽  
Arterial Pressure ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Sleep Fragmentation ◽  
Cardiovascular Pathology ◽  
Acid Producing Bacteria ◽  
Gut Microbial Community

The gut microbiota, via the production of metabolites entering the circulation, plays a role in blood pressure regulation. Blood pressure is also affected by the characteristics of sleep. To date, no studies have examined relationships among the gut microbiota/metabolites, blood pressure, and sleep. We hypothesized that fragmented sleep is associated with elevated mean arterial pressure, an altered and dysbiotic gut microbial community, and changes in fecal metabolites. In our model system, rats were randomized to 8 h of sleep fragmentation during the rest phase (light phase) or were undisturbed (controls) for 28 consecutive days. Rats underwent sleep and blood pressure recordings, and fecal samples were analyzed during: baseline ( days −4 to −1), early sleep fragmentation ( days 0–3), midsleep fragmentation ( days 6–13), late sleep fragmentation ( days 20–27), and recovery/rest ( days 28–34). Less sleep per hour during the sleep fragmentation period was associated with increased mean arterial pressure. Analyses of gut microbial communities and metabolites revealed that putative short chain fatty acid-producing bacteria were differentially abundant between control and intervention animals during mid-/late sleep fragmentation and recovery. Midsleep fragmentation was also characterized by lower alpha diversity, lower Firmicutes:Bacteroidetes ratio, and higher Proteobacteria in intervention rats. Elevated putative succinate-producing bacteria and acetate-producing bacteria were associated with lower and higher mean arterial pressure, respectively, and untargeted metabolomics analysis demonstrates that certain fecal metabolites are significantly correlated with blood pressure. These data reveal associations between sleep fragmentation, mean arterial pressure, and the gut microbiome/fecal metabolome and provide insight to links between disrupted sleep and cardiovascular pathology.

scholarly journals The Gut Microbiota Is Associated with Vascular Function and Blood Pressure Phenotypes in Overweight and Obese Middle-Aged/Older Adults (P21-024-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sarah Johnson ◽  
Nicole Litwin ◽  
Hannah Van Ark ◽  
Shannon Hartley ◽  
Emily Fischer ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Stiffness ◽  
Gut Microbiota ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Reactive Hyperemia ◽  
Bifidobacterium Longum ◽  
Middle Aged ◽  
Principal Coordinates ◽  
The Relationship

Abstract Objectives The gut microbiota is emerging as an important regulator of cardiovascular health. Indeed, gut dysbiosis is increasingly being linked to the development of cardiovascular disease (CVD). Aging and obesity are associated with the development of CVD largely due to the development of vascular dysfunction, namely endothelial dysfunction and arterial stiffness. The objective of this study was to examine the relationship between the gut microbiota, blood pressure, and vascular function in aging overweight and obese individuals. Methods This cross-sectional study included fifteen overweight and obese (mean body mass index, BMI: 29.5; range: 25.8–37.0) middle-aged/older men and postmenopausal women (mean age: 53; range: 42–64 years). Blood pressure, arterial stiffness (augmentation index, AIx, and aortic pulse wave velocity, aPWV), and endothelial function (reactive hyperemia index, RHI) were assessed. Stool samples were collected for gut microbiota analysis using 16S ribosomal RNA sequencing. Principal coordinates analysis and Pearson's correlations were performed to evaluate the relationship between the gut microbiota and measures of vascular function and blood pressure. Results Global gut microbiota phenotypes clustered most strongly by aPWV (groups separated by median value) as visualized by Non-Metric Dimensional Scaling plot of Bray-Curtis Distances (stress = 0.09; P = 0.07). Several bacterial taxa correlated with vascular parameters. For example, Bifidobacterium longum (r = 0.80, P < 0.001) and Akkermansia muciniphila (r = 0.56, P = 0.047) were positively correlated with RHI. Bifdobacterium bifidum (r = −0.61, P = 0.02) and Oxalobacter formigenes (r = −0.62, P = 0.02) were negatively correlated with systolic blood pressure. Interestingly, there was no significant clustering by BMI groupings (overweight vs. obese) or correlations between BMI and specific taxa. Conclusions These preliminary data suggest that the gut microbiota is linked to vascular dysfunction and increased blood pressure in aging overweight and obese individuals independent of BMI. Further data collection and analysis are currently underway to explore these relationships in a larger human cohort, and to explore underlying mechanisms through transferring of vascular phenotypes in humans to germ-free mice through microbiota transplantation. Funding Sources NIFA, USDA.

Abstract 649: Endothelial-derived Sphingolipids Preserve Systemic Vascular Function And Blood Pressure

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Anna Cantalupo ◽  
Yi Zhang ◽  
Hideru Obinata ◽  
Syvain Galvain ◽  
Xiang-Cheng Jiang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Critical Event ◽  
Ang Ii ◽  
Serine Palmitoyltransferase ◽  
Induced Hypertension

Endothelial dysfunction is a critical event in many cardiovascular diseases including hypertension. Although lipid signaling is implicated in endothelial dysfunction and cardiovascular diseases, specific molecular mechanisms are poorly understood. Here we report a novel regulation of endothelial sphingolipid synthesis by Nogo-B, membrane protein of the endoplasmic reticulum that modulates local sphingolipid production with direct effects on vascular function and blood pressure. Nogo-B inhibits serine palmitoyltransferase, rate-limiting enzyme of the sphingolipid de novo synthesis, controlling endothelial sphingosine 1-phosphate production and its autocrine G-protein-coupled receptor-dependent signaling actions. Mice lacking Nogo-B are hypotensive (90.1±1.6 vs. 119.9±2.6 mmHg WT mice), resistant to Ang-II (500ng/Kg/min)-induced hypertension (150.4±2.5 vs. 108.4±1.5 mmHg, compared to WT mice, 24 days after AngII infusion), and preserve endothelial function and nitric oxide release. Pharmacological inhibition of serine palmitoyltransferase with myriocin in mice that lack Nogo-B reinstated endothelial dysfunction and Ang-II-induced hypertension (143.9±1.5 vs. 90.1±1.6 mmHg, myriocin vs. vehicle treated Nogo-A/B-/- mice). Our study identifies Nogo-B as a key inhibitor of local sphingolipid synthesis and indicates that autocrine sphingolipids signaling within the endothelium are critical for vascular function and blood pressure homeostasis.

scholarly journals Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction

Gut ◽  
2017 ◽  
Vol 67 (2) ◽  
pp. 271-283 ◽  
Author(s):  
Emilie Catry ◽  
Laure B Bindels ◽  
Anne Tailleux ◽  
Sophie Lestavel ◽  
Audrey M Neyrinck ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Gut Microbiota ◽  
Vascular Function ◽  
Carotid Arteries ◽  
Rrna Gene ◽  
Gut Peptides ◽  
Novel Approach

ObjectiveTo investigate the beneficial role of prebiotics on endothelial dysfunction, an early key marker of cardiovascular diseases, in an original mouse model linking steatosis and endothelial dysfunction.DesignWe examined the contribution of the gut microbiota to vascular dysfunction observed in apolipoprotein E knockout (Apoe−/−) mice fed an n-3 polyunsaturated fatty acid (PUFA)-depleted diet for 12 weeks with or without inulin-type fructans (ITFs) supplementation for the last 15 days. Mesenteric and carotid arteries were isolated to evaluate endothelium-dependent relaxation ex vivo. Caecal microbiota composition (Illumina Sequencing of the 16S rRNA gene) and key pathways/mediators involved in the control of vascular function, including bile acid (BA) profiling, gut and liver key gene expression, nitric oxide and gut hormones production were also assessed.ResultsITF supplementation totally reverses endothelial dysfunction in mesenteric and carotid arteries of n-3 PUFA-depleted Apoe−/− mice via activation of the nitric oxide (NO) synthase/NO pathway. Gut microbiota changes induced by prebiotic treatment consist in increased NO-producing bacteria, replenishment of abundance in Akkermansia and decreased abundance in bacterial taxa involved in secondary BA synthesis. Changes in gut and liver gene expression also occur upon ITFs suggesting increased glucagon-like peptide 1 production and BA turnover as drivers of endothelium function preservation.ConclusionsWe demonstrate for the first time that ITF improve endothelial dysfunction, implicating a short-term adaptation of both gut microbiota and key gut peptides. If confirmed in humans, prebiotics could be proposed as a novel approach in the prevention of metabolic disorders-related cardiovascular diseases.

Abstract 427: Mammalian Target of Rapamycin (mTOR) Inhibition Attenuates Angiotensin II-Induced Hypertension and Endothelial Dysfunction

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Sean P Didion ◽  
Joel A Sarmiento ◽  
Erin M Mezzetti
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Carotid Arteries ◽  
Mammalian Target Of Rapamycin ◽  
Significant Degree ◽  
Molecular Evidence ◽  
Ang Ii ◽  
Mtor Inhibition

Angiotensin (Ang) II produces hypertension, endothelial dysfunction as well as vascular hypertrophy. mTOR is a key regulator of cell growth and protein synthesis, however the contribution of mTOR to hypertension and endothelial dysfunction produced by Ang II has not been previously elucidated. The goal of this study was to test the hypothesis that mTOR contributes to the hypertension and endothelial dysfunction produced by Ang II. C57Bl/6 mice were infused (via osmotic minipump) with vehicle or rapamycin (an inhibitor of mTOR; 2 mg/kg/d) for 10 days following which mice were then infused with Ang II (1000 ng/kg/min) plus vehicle or rapamycin for 14 subsequent days. Systolic blood pressure (SBP) was measured on Days -10, 0, and 14 using tail-cuff plethysmography and vascular function was examined in carotid arteries (in vitro) on Day 14. Ang II infusion produced a significant degree (P<0.05) of hypertension in wild-type mice (eg, SBP: 114±4 vs. 145±3 mmHg on Day 0 and Day 14 of Ang II infusion, respectively). In rapamycin-treated mice, Ang II infusion had no effect (P>0.05) on SBP (eg, SBP: 110±6 vs. 116±9 mmHg, on Day 0 and Day 14 of co-infusion of rapamycin plus Ang II, respectively). Rapamycin alone or vehicle infusion had no effect (P>0.05) on blood pressure during Day -10 through Day 0. In terms of endothelial responses, acetylcholine-induced relaxation was impaired (P<0.05) in Ang II-infused mice by approximately 50%. In contrast, rapamycin was associated with a significant degree of protection against Ang II-induced endothelial dysfunction (eg, 100 μM acetylcholine produced 47±10 vs. 90±4% relaxation in carotid arteries from Ang II- and Ang II plus rapamycin-infused mice, respectively). Tempol, a scavenger of superoxide was very effective in improving endothelial responses in Ang II-infused mice. Molecular analysis revealed that Ang II-infusion was associated with increased mTOR expression as well as mTOR phosphorylation. Taken together, these data provide strong pharmacologic and molecular evidence that mTOR activity contributes to the hypertension and endothelial dysfunction produced by Ang II.

scholarly journals Endothelial-specific CYP4A2 overexpression leads to renal injury and hypertension via increased production of 20-HETE

2009 ◽  
Vol 297 (4) ◽  
pp. F875-F884 ◽  
Author(s):  
Kazuyoshi Inoue ◽  
Komal Sodhi ◽  
Nitin Puri ◽  
Katherine H. Gotlinger ◽  
Jiang Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Renal Injury ◽  
Vascular Function ◽  
Vascular Endothelial ◽  
Sprague Dawley ◽  
Sd Rats ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We have previously reported that adenoviral-mediated delivery of cytochrome P-450 (CYP) 4A2, which catalyzes the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), results in endothelial dysfunction and hypertension in Sprague-Dawley (SD) rats (Wang JS, Singh H, Zhang F, Ishizuka T, Deng H, Kemp R, Wolin MS, Hintze TH, Abraham NG, Nasjletti A, Laniado-Schwartzman M. Circ Res 98: 962–969, 2006). In this study, we targeted the vascular endothelium by using a lentivirus construct expressing CYP4A2 under the control of the endothelium-specific promoter VE-cadherin (VECAD-4A2) and examined the effect of long-term CYP4A2 overexpression on blood pressure and kidney function in SD rats. A bolus injection of VECAD-4A2 increased blood pressure ( P < 0.001) by 26, 36, and 30 mmHg 10, 20, and 30 days postinjection, respectively. Arteries from VECAD-4A2-transduced rats produced increased levels of 20-HETE ( P < 0.01), expressed lower levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) ( P < 0.05), generated higher levels of superoxide anion, and displayed decreased relaxing responsiveness to acetylcholine ( P < 0.05). Proteinuria increased by twofold in VECAD-4A2-transduced rats compared with controls. Treatment of VECAD-4A2-transduced rats with HET0016, an inhibitor of 20-HETE biosynthesis, not only attenuated the increase in blood pressure ( P < 0.05) but also improved vascular function (acetylcholine-induced relaxations) and reduced plasma creatinine and proteinuria. HET0016 treatment decreased oxidative stress and increased the phosphorylated state of key proteins that regulate endothelial function, including eNOS, AKT, and AMPK. Collectively, these findings demonstrate that augmentation of vascular endothelial 20-HETE levels results in hypertension, endothelial dysfunction, and renal injury, which is offset by HET0016 through a reduction in vascular 20-HETE coupled with a lessening of oxidative stress and the amplification of pAKT, pAMPK, and p-eNOS levels leading to normalization of endothelial responses.

scholarly journals Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction

2018 ◽  
Vol 314 (5) ◽  
pp. E468-E477 ◽  
Author(s):  
Micah L. Battson ◽  
Dustin M. Lee ◽  
Dillon K. Jarrell ◽  
Shuofei Hou ◽  
Kayl E. Ecton ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Arterial Stiffness ◽  
Gut Microbiota ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Nuclear Factor Κb ◽  
Western Diet ◽  
Standard Diet ◽  
Vascular Abnormalities ◽  
Gut Dysbiosis

Vascular dysfunction represents a critical preclinical step in the development of cardiovascular disease. We examined the role of the gut microbiota in the development of obesity-related vascular dysfunction. Male C57BL/6J mice were fed either a standard diet (SD) ( n = 12) or Western diet (WD) ( n = 24) for 5 mo, after which time WD mice were randomized to receive either unsupplemented drinking water or water containing a broad-spectrum antibiotic cocktail (WD + Abx) ( n = 12/group) for 2 mo. Seven months of WD caused gut dysbiosis, increased arterial stiffness (SD 412.0 ± 6.0 vs. WD 458.3 ± 9.0 cm/s, P < 0.05) and endothelial dysfunction (28% decrease in max dilation, P < 0.05), and reduced l-NAME-inhibited dilation. Vascular dysfunction was accompanied by significant increases in circulating LPS-binding protein (LBP) (SD 5.26 ± 0.23 vs. WD 11 ± 0.86 µg/ml, P < 0.05) and interleukin-6 (IL-6) (SD 3.27 ± 0.25 vs. WD 7.09 ± 1.07 pg/ml, P < 0.05); aortic expression of phosphorylated nuclear factor-κB (p-NF-κB) ( P < 0.05); and perivascular adipose expression of NADPH oxidase subunit p67phox ( P < 0.05). Impairments in vascular function correlated with reductions in Bifidobacterium spp. Antibiotic treatment successfully abrogated the gut microbiota and reversed WD-induced arterial stiffness and endothelial dysfunction. These improvements were accompanied by significant reductions in LBP, IL-6, p-NF-κB, and advanced glycation end products (AGEs), and were independent from changes in body weight and glucose tolerance. These results indicate that gut dysbiosis contributes to the development of WD-induced vascular dysfunction, and identify the gut microbiota as a novel therapeutic target for obesity-related vascular abnormalities.

scholarly journals NADPH oxidase 4 has a crucial impact on the microcirculation of hypercholesteremic LDL receptor deficient mice

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
P Diaba-Nuhoho ◽  
A Shahid ◽  
C Brunssen ◽  
H Morawietz ◽  
H Brendel
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Mouse Model ◽  
Nadph Oxidase ◽  
Endothelial Function ◽  
Vascular Function ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Enos Expression ◽  
Small Resistance

Abstract Introduction NADPH oxidase (NOX) 4-generated H2O2 has anti-atherosclerotic properties in conduit arteries like the aorta and carotids. However, the role of NOX4 on vascular function of small resistance arteries and blood pressure in a mouse model of familial hypercholesterolemia is unknown. Purpose We evaluated whether NOX4-generated H2O2 might play a role in perivascular adipose tissue of the thoracic aorta (tPVAT) and small resistance arteries on vascular function in a mouse model of familial hypercholesterolemia. Methods Aortic segments and mesenteric arteries from 26-week-old Ldlr−/− and Nox4−/− / Ldlr−/− mice were analysed by Mulvany myograph. In addition, vascular contraction and relaxation was analysed in the presence of L-NAME and catalase. Analysis of mRNA expression was performed in murine and human tissue by quantitative real-time PCR. Blood pressure was detected by tail cuff method in conscious, trained mice. Results Loss of NOX4 led to severe endothelial dysfunction in mesenteric arteries of Ldlr−/− mice. Blocking of NO synthases with L-NAME led to decreased endothelial relaxation in Ldlr−/− mice at the level of Nox4−/− / Ldlr−/− mice. However, incubation with L-NAME did not worsen the established endothelial dysfunction of the mesenteric arteries from Nox4−/− / Ldlr−/− mice. These results are strikingly different from the aorta, where inhibition of NO synthases led to a similarly impaired endothelial relaxation in both mouse strains. We detected a similar eNOS expression in the aorta of Ldlr−/− and Nox4−/− / Ldlr−/−, but a reduced eNOS expression in the mesenteric arteries of Nox4−/− / Ldlr−/− mice. H2O2 can induce eNOS expression. Therefore, we analysed the vascular function after catalase incubation and again found a significant reduction of endothelial function in the mesenteric arteries of Ldlr−/− mice. Finally, we analysed blood pressure of these mice and did not observe differences in systolic blood pressure, despite significant differences in endothelial function of resistant arteries. Conclusion NOX4 protects against severe endothelial dysfunction in the mesenteric artery in a model of hypercholesterolemia. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): Ghanaian-German postgraduate training scholarship program (DAAD)

scholarly journals Transmission of raised blood pressure and endothelial dysfunction to the F2generation induced by maternal protein restriction in the F0, in the absence of dietary challenge in the F1generation

2008 ◽  
Vol 100 (4) ◽  
pp. 760-766 ◽  
Author(s):  
Christopher Torrens ◽  
Lucilla Poston ◽  
Mark A. Hanson
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Protein Restriction ◽  
Mesenteric Arteries ◽  
Maximal Response ◽  
Maternal Line ◽  
Maternal Protein Restriction ◽  
Female Wistar Rats ◽  
Protein Restricted Diet

We have previously demonstrated that maternal protein restriction during pregnancy leads to raised blood pressure and endothelial dysfunction in the offspring (F1). Here we show that these characteristics are transmitted to the F2offspring through the maternal line, in the absence of any additional challenges to the F1. Female Wistar rats were fed either a control (18 % casein) or protein-restricted diet (PR; 9 % casein) throughout pregnancy. Female F1offspring, maintained on standard chow postpartum, were mated with breeding males to produce F2progeny. Systolic blood pressure (SBP) in male F2offspring was assessed by tail-cuff plethysmography at age 100 d and vascular function of small mesenteric arteries by wire myography at age 80 and 200 d. SBP was raised in PR F2offspring compared with controls (control 122·1 (sem2·3) mmHg,n7; PR 134·7 (sem3·2) mmHg,n6;P < 0·01) and endothelial function, assessed by vasodilatation to acetylcholine, was impaired at both age 80 d (% maximal response: control 89·7 (sem2·6),n14; PR 72·7 (sem4·4),n15;P < 0·01) and 200 d (effective concentration equal to 50 % of maximum (pEC50): control 7·67 (sem0·10),n10; PR 7·33 (sem0·07),n8;P < 0·05). The present study demonstrates that both raised blood pressure and endothelial dysfunction are passed via the maternal line to grand-offspring in the absence of any additional dietary challenges to their F1mothers. Risk factors for chronic disease may therefore be heritable by non-genomic processes.

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