Abstract P264: Endothelial-specific Interference With PPARγ Activity in Offspring Born From AVP-induced Preeclamptic Pregnancies Has Cardio-renal and Metabolic Consequences

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Anand R Nair ◽  
Masashi Mukohda ◽  
Larry N Agbor ◽  
Ko-Ting Lu ◽  
Jing Wu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Female Offspring ◽  
Reduce Blood Pressure ◽  
Dominant Negative ◽  
Peroxisome Proliferator ◽  
Hypertensive Disorder ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Impact

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor known to regulate metabolic and vascular function. Mutations in PPARγ result in hypertension, and synthetic agonists of PPARγ reduce blood pressure. Previously we found that mice expressing dominant-negative (DN) PPARγ driven by an endothelium-specific promoter (E-DN) exhibit vascular dysfunction. Preeclampsia (PE) is a hypertensive disorder of pregnancy which carries cardiovascular and metabolic risk to offspring. PE is associated with vascular dysfunction, and we therefore hypothesized a role for endothelial PPARγ in the pathogenesis of PE and its sequelae. C57BL/6J dams were bred with E-DN sires, and symptoms of PE were induced by the infusion of vasopressin (AVP, 24 ng/hr sc) throughout gestation. We assessed phenotypes of PE first in pregnant dams, and then in offspring as adults. Compared to saline infusion (SAL), AVP elevated maternal blood pressure (SBP: 116±3 vs 107±3, p<0.05) at gestational day (GD) 14-15 and urine protein (70±6 vs 27±4 mg/mL, p<0.05) at GD17. Offspring from these pregnancies were phenotyped in adulthood to assess cardiovascular and metabolic function. Data were stratified to sex, genotype, and maternal exposure to AVP vs SAL. Systolic blood pressure in adult male and female offspring born to AVP-infused pregnancies was similar to mice born to SAL pregnancies. At 20 weeks of age, vasorelaxation responses to acetylcholine were not different in offspring exposed to PE compared to mice born from SAL pregnancies. However, urinary protein levels were significantly elevated in both male (58±13 vs 32±5 mg/ml, p<0.05) and female (38±3 vs 25±2 mg/ml, p<0.05) adult E-DN born to PE pregnancies compared to E-DN controls born from SAL pregnancies. Male E-DN offspring exposed to PE showed significantly increased gain in body weight over time compared to male NT exposed to PE (ΔBW: 20±8 vs 14±2 g). These data highlight the impact of in utero exposure to elevated AVP upon cardiovascular function in the mother, and the adverse renal and metabolic consequences of PE upon offspring. Moreover, our data suggests that interference with endothelial PPARγ in pups born from PE pregnancies increases the risk for renal and metabolic dysfunction.

Abstract 310: Deoxycorticosterone Acetate (doca)-salt Exacerbates Hypertension and Vascular Dysfunction in Mice Expressing Dominant Negative Peroxisome Proliferator-activated Receptor-gamma (pparg) in Smooth Muscle

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Pimonrat Ketsawatsomkron ◽  
Deborah R Davis ◽  
Aline M Hilzendeger ◽  
Justin L Grobe ◽  
Curt D Sigmund
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Transgenic Mice ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Critical Role ◽  
Surrogate Marker ◽  
Dominant Negative ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

PPARG, a ligand-activated transcription factor plays a critical role in the regulation of blood pressure and vascular function. We hypothesized that smooth muscle cell (SMC) PPARG protects against hypertension (HT) and resistance vessel dysfunction. Transgenic mice expressing dominant negative PPARG (S-P467L) in SMC or non-transgenic controls (NT) were implanted with DOCA pellet and allowed ad libitum access to 0.15 M NaCl for 21 days in addition to regular chow and water. Blood pressure was monitored by telemetry and mesenteric arterial (MA) function was assessed by pressurized myograph. At baseline, 24-hour mean arterial pressure (MAP) was similar between NT and S-P467L mice, while the transgenic mice were tachycardic. DOCA-salt increased MAP to a much greater degree in S-P467L mice (Δ MAP; S-P467L: +34.2±6.0, NT: +13.3±5.7, p<0.05 vs NT). Heart rate was similarly decreased in both groups after DOCA-salt. Vasoconstriction to KCl, phenylephrine and endothelin-1 did not differ in MA from DOCA-salt treated NT and S-P467L, while the response to vasopressin was significantly reduced in S-P467L after DOCA-salt (% constriction at 10-8 M, S-P467L: 31.6±5.6, NT: 46.7±3.8, p<0.05 vs NT). Urinary copeptin, a surrogate marker for arginine vasopressin was similar in both groups regardless of treatment. Vasorelaxation to acetylcholine was slightly impaired in S-P467L MA compared to NT at baseline whereas this effect was further exaggerated after DOCA-salt (% relaxation at 10-5 M, S-P467L: 56.1±8.3, NT: 79.4±5.6, p<0.05 vs NT). Vascular morphology at luminal pressure of 75 mmHg showed a significant increase in wall thickness (S-P467L: 18.7±0.8, NT: 16.0±0.4, p<0.05 vs NT) and % media/lumen (S-P467L: 8.4±0.3, NT: 7.1±0.2, p<0.05 vs NT) in S-P467L MA after DOCA-salt. Expression of tissue inhibitor of metalloproteinases (TIMP)-4 and regulator of G-protein signaling (RGS)-5 transcript were 2- and 3.5-fold increased, respectively, in MA of NT with DOCA-salt compared to NT baseline. However, this induction was markedly blunted in S-P467L MA. We conclude that interference with PPARG function in SMC leads to altered gene expression crucial for normal vascular homeostasis, thereby sensitizing the mice to the effects of DOCA-salt induced HT and vascular dysfunction.

Abstract 331: Mutation in the PPARG Ligand Binding Domain Impairs PPARG-Mediated Turnover of the p65 Subunit of NF-kB

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Masashi Mukoda ◽  
Madeliene Stump ◽  
Pimonrat Ketsawatsomkron ◽  
Frederick W Quelle ◽  
Curt D Sigmund
Keyword(s):  
Vascular Function ◽  
Nuclear Factor Kappa B ◽  
Vascular Dysfunction ◽  
Direct Interaction ◽  
Dominant Negative ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Transfected Cells ◽  
Over Expression ◽  
Pparγ Agonist

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand activated transcription factor regulating metabolic and vascular function. PPARγ exerts anti-inflammatory actions, and recent data suggest this may be mediated by promoting the degradation of the p65 subunit of nuclear factor kappa B (NFκB). Transgenic mice expressing dominant negative PPARγ specifically in vascular smooth muscle or endothelium exhibited exacerbated atherosclerosis but the mechanism remains unknown. We hypothesized that PPARγ mutants promote inflammation because PPARγ-mediated p65 degradation is impaired. We tested this by co-transfection of HEK293T cells with vectors encoding p65, wildtype (WT) PPARγ, or various PPARγ mutants. The level of p65 protein expression was decreased by co-expression with WT-PPARγ (0.53±0.09 vs control, n=8). Whereas, the P467L PPARγ exhibited impaired degradation of p65 (1.0±0.06, n=10), the V290M (0.36±0.1), S273A (0.37±0.06), or K268R/K293R (0.41±0.03) mutations in PPARγ preserved p65 degradation. WT PPARγ was co-precipitated with p65 in co-transfected cells suggesting the mechanism of PPARγ-mediated p65 degradation involves a direct interaction between them. Consistent with this, the interaction between p65 and P467L PPARγ was severely impaired. To assess functional interactions between PPARγ and NFκB, we employed a model of interleukin-1β (IL-1β) mediated dysfunction in aortic rings. IL-1β dose-dependently induced NFκB activity as measured by increased phospho-p65 and decreased IκBα in aorta cultured for 2 hours with IL-1β. IL-1β dose-dependently reduced acetylcholine (Ach)-induced endothelial-dependent relaxation of aortic rings (80±12 vs 39±16, 20 pg/mL vs 11±3, 100 pg/mL, %). IL-1β-mediated loss of Ach vasodilation was reduced by the PPARγ agonist rosiglitazone (1 μM, 25 hr, n=3, p<0.05), or by transgenic over-expression of WT-PPARγ specifically in endothelium (n=6, p<0.05). We conclude that 1) p65 turnover may be regulated by PPARγ and that its mutation can result in impaired p65 degradation, 2) PPARγ activity can protect against vascular dysfunction associated with NFκB activation, and 3) loss of PPARγ-mediated p65 degradation may contribute to inflammation in hypertension and atherosclerosis.

Abstract 053: RhoBTB1 is a Novel Gene Protecting Against Hypertension

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Masashi Mukohda ◽  
Stella-Rita C Ibeawuchi ◽  
Chunyan Hu ◽  
Ko-Ting Lu ◽  
Debbie R Davis ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Thoracic Aorta ◽  
Basilar Artery ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Dominant Negative ◽  
Tamoxifen Treatment ◽  
Peroxisome Proliferator ◽  
Ang Ii ◽  
Peroxisome Proliferator Activated Receptor

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand activated transcription factor regulating metabolic and vascular function. We previously reported that mice (S-DN) expressing dominant-negative PPARγ in smooth muscle cells (SMC) are hypertensive, exhibit impaired vascular relaxation and enhanced contraction, and display reduced expression of a novel PPARγ target gene, RhoBTB1. We hypothesized that RhoBTB1 may play a protective role in vascular function that is disrupted in S-DN mice and in other models of hypertension. We generated double transgenic mice (termed R+) with tamoxifen-inducible, Cre-dependent expression of RhoBTB1 in SMC. R+ mice were crossed with S-DN to produce mice (S-DN/R+) in which tamoxifen-treatment (75 mg/kg, ip, 5 days) restored RhoBTB1 expression in aorta to normal. Thoracic aorta and basilar artery from S-DN showed impaired acetylcholine (ACh)-induced endothelial-dependent relaxation, which was reversed by replacement of RhoBTB1 in SMC (thoracic aorta, 43.3±4.4 vs 74.2±1.1%, p<0.01, basilar artery, 19.9±6.7 vs 48.1±12.3%, p<0.05, n=6). Aorta from S-DN mice also displayed severely decreased sodium nitroprusside (SNP)-induced endothelial-independent relaxation with a right-shifted dose-response, which was also reversed in tamoxifen-treated S-DN/R+ mice (p<0.01, n=6). Importantly, replacement of RhoBTB1 also reversed the hypertensive phenotype observed in S-DN mice (Radiotelemetry SBP, 135.9±3.9 vs 123.7±3.0 mmHg, p<0.05, n=4). To examine if overexpression of RhoBTB1 in SMC has a protective effect on other hypertensive models, Ang-II (490 ng/min/kg) was infused in tamoxifen treated R+ mice for 2 wks. RhoBTB1 expression prevented Ang-II-induced impairment of ACh relaxation in basilar artery (17.0±8.6 in control mice vs 40.7±5.3 % in R+ mice, p<0.05, n=4) and decreased SBP (166.0±7.2 in control mice vs 133.3±5.1 mmHg in R+ mice, p<0.05, n=4). We conclude that a) loss of RhoBTB1 function explains the vascular dysfunction and hypertension observed in response to interference with PPARγ in smooth muscle, and b) RhoBTB1 in SMC has an anti-hypertensive effect and facilitates vasodilatation.

scholarly journals Regulator of G protein signaling 5 is a determinant of gestational hypertension and preeclampsia

2015 ◽  
Vol 7 (290) ◽  
pp. 290ra88-290ra88 ◽  
Author(s):  
Vasyl Holobotovskyy ◽  
Yee Seng Chong ◽  
Jennifer Burchell ◽  
Bo He ◽  
Michael Phillips ◽  
...  
Keyword(s):  
Blood Pressure ◽  
G Protein ◽  
Vascular Function ◽  
Gestational Hypertension ◽  
Peroxisome Proliferator ◽  
Protein Signaling ◽  
Current Standard ◽  
Guanine Nucleotide Binding Protein ◽  
Peroxisome Proliferator Activated Receptor

Preeclampsia is a systemic vascular disorder of pregnancy and is associated with increased sensitivity to angiotensin II (AngII) and hypertension. The cause of preeclampsia remains unknown. We identified the role of regulator of G protein (heterotrimeric guanine nucleotide–binding protein) signaling 5 (RGS5) in blood pressure regulation during pregnancy and preeclampsia. RGS5 expression in human myometrial vessels is markedly suppressed in gestational hypertension and/or preeclampsia. In pregnant RGS5-deficient mice, reduced vascular RGS5 expression causes gestational hypertension by enhancing vascular sensitivity to AngII. Further challenge by increasing AngII results in preeclampsia-like symptoms, namely, more severe hypertension, proteinuria, placental pathology, and reduced birth weight. In pregnant heterozygote null mice, treatment with peroxisome proliferator–activated receptor (PPAR) agonists normalizes vascular function and blood pressure through effects on RGS5. These findings highlight a key role of RGS5 at the interface between AngII and PPAR signaling. Because preeclampsia is refractory to current standard therapies, our study opens an unrecognized and urgently needed opportunity for treatment of gestational hypertension and preeclampsia.

scholarly journals Salt-Sensitivity of Blood Pressure and Insulin Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Lale A. Ertuglu ◽  
Fernando Elijovich ◽  
Cheryl L. Laffer ◽  
Annet Kirabo
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Immune Activation ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Salt Sensitivity ◽  
Common Denominator ◽  
Peroxisome Proliferator ◽  
Cardiovascular Morbidity And Mortality

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality that is seen in both hypertensive and normotensive populations. Insulin resistance (IR) strongly correlates with SSBP and affects nearly 50% of salt sensitive people. While the precise mechanism by which IR and SSBP relate remains elusive, several common pathways are involved in the genesis of both processes, including vascular dysfunction and immune activation. Vascular dysfunction associated with insulin resistance is characterized by loss of nitric oxide (NO)-mediated vasodilation and heightened endothelin-1 induced vasoconstriction, as well as capillary rarefaction. It manifests with increased blood pressure (BP) in salt sensitive murine models. Another common denominator in the pathogenesis of insulin resistance, hypertension, and salt sensitivity (SS) is immune activation involving pro-inflammatory cytokines like tumor necrosis factor (TNF)-α, IL-1β, and IL-6. In the last decade, a new understanding of interstitial sodium storage in tissues such as skin and muscle has revolutionized traditional concepts of body sodium handling and pathogenesis of SS. We have shown that interstitial Na+ can trigger a T cell mediated inflammatory response through formation of isolevuglandin protein adducts in antigen presenting cells (APCs), and that this response is implicated in salt sensitive hypertension. The peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that modulates both insulin sensitivity and BP. PPARγ agonists increase insulin sensitivity and ameliorate salt sensitivity, whereas deficiency of PPARγ results in severe insulin resistance and hypertension. These findings suggest that PPARγ plays a role in the common pathogenesis of insulin sensitivity and salt sensitivity, perhaps via effects on the immune system and vascular function. The goal of this review is to discuss those mechanisms that may play a role in both SSBP and in insulin resistance.

scholarly journals 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: The role of the mineralocorticoid receptor in the vasculature

2017 ◽  
Vol 234 (1) ◽  
pp. T67-T82 ◽  
Author(s):  
Jennifer J DuPont ◽  
Iris Z Jaffe
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Mineralocorticoid Receptor ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Kidney Injury ◽  
Vascular Pathology ◽  
The Impact

Since the mineralocorticoid receptor (MR) was cloned 30 years ago, it has become clear that MR is expressed in extra-renal tissues, including the cardiovascular system, where it is expressed in all cells of the vasculature. Understanding the role of MR in the vasculature has been of particular interest as clinical trials show that MR antagonism improves cardiovascular outcomes out of proportion to changes in blood pressure. The last 30 years of research have demonstrated that MR is a functional hormone-activated transcription factor in vascular smooth muscle cells and endothelial cells. This review summarizes advances in our understanding of the role of vascular MR in regulating blood pressure and vascular function, and its contribution to vascular disease. Specifically, vascular MR contributes directly to blood pressure control and to vascular dysfunction and remodeling in response to hypertension, obesity and vascular injury. The literature is summarized with respect to the role of vascular MR in conditions including: pulmonary hypertension; cerebral vascular remodeling and stroke; vascular inflammation, atherosclerosis and myocardial infarction; acute kidney injury; and vascular pathology in the eye. Considerations regarding the impact of age and sex on the function of vascular MR are also described. Further investigation of the precise molecular mechanisms by which MR contributes to these processes will aid in the identification of novel therapeutic targets to reduce cardiovascular disease (CVD)-related morbidity and mortality.

scholarly journals Mechanisms of vascular dysfunction in mice with endothelium-specific deletion of the PPAR-δ gene

2014 ◽  
Vol 306 (7) ◽  
pp. H1001-H1010 ◽  
Author(s):  
Livius V. d'Uscio ◽  
Tongrong He ◽  
Anantha Vijay R. Santhanam ◽  
Li-Jung Tai ◽  
Ronald M. Evans ◽  
...  
Keyword(s):  
Vascular Function ◽  
Vascular Dysfunction ◽  
Vascular Endothelial Cell ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Superoxide Anion Production ◽  
No Donor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Specific Deletion

Peroxisome proliferator-activated receptor (PPAR)-δ is a nuclear hormone receptor that is mainly involved in lipid metabolism. Recent studies have suggested that PPAR-δ agonists exert vascular protective effects. The present study was designed to characterize vascular function in mice with genetic inactivation of PPAR-δ in the endothelium. Mice with vascular endothelial cell-specific deletion of the PPAR-δ gene (ePPARδ−/− mice) were generated using loxP/Cre technology. ePPARδ−/− mice were normotensive and did not display any sign of metabolic syndrome. Endothelium-dependent relaxations to ACh and endothelium-independent relaxations to the nitric oxide (NO) donor diethylammonium ( Z)-1-( N, N-diethylamino)diazen-1-ium-1,2-diolate were both significantly impaired in the aorta and carotid arteries of ePPARδ−/− mice ( P < 0.05). In ePPARδ−/− mouse aortas, phosphorylation of endothelial NO synthase at Ser1177 was significantly decreased ( P < 0.05). However, basal levels of cGMP were unexpectedly increased ( P < 0.05). Enzymatic activity of GTP-cyclohydrolase I and tetrahydrobiopterin levels were also enhanced in ePPARδ−/− mice ( P < 0.05). Most notably, endothelium-specific deletion of the PPAR-δ gene significantly decreased protein expressions of catalase and glutathione peroxidase 1 and resulted in increased levels of H2O2 in the aorta ( P < 0.05). In contrast, superoxide anion production was unaltered. Moreover, treatment with catalase prevented the endothelial dysfunction and elevation of cGMP detected in aortas of ePPARδ−/− mice. The findings suggest that increased levels of cGMP caused by H2O2 impair vasodilator reactivity to endogenous and exogenous NO. We speculate that chronic elevation of H2O2 predisposes PPAR-δ-deficient arteries to oxidative stress and vascular dysfunction.

scholarly journals Failure to vasodilate in response to salt loading blunts renal blood flow and causes salt-sensitive hypertension

2020 ◽  
Author(s):  
Jing Wu ◽  
Larry N Agbor ◽  
Shi Fang ◽  
Masashi Mukohda ◽  
Anand R Nair ◽  
...  
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Renal Blood Flow ◽  
Vascular Dysfunction ◽  
Dominant Negative ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Salt Loading ◽  
Dominant Negative Mutation ◽  
Induced Hypertension

Abstract Aims Salt-sensitive (SS) hypertension is accompanied by impaired vasodilation in the systemic and renal circulation. However, the causal relationship between vascular dysfunction and salt-induced hypertension remains controversial. We sought to determine whether primary vascular dysfunction, characterized by a failure to vasodilate during salt loading, plays a causal role in the pathogenesis of SS hypertension. Methods and results Mice selectively expressing a peroxisome proliferator-activated receptor γ dominant-negative mutation in vascular smooth muscle (S-P467L) exhibited progressive SS hypertension during a 4 week high salt diet (HSD). This was associated with severely impaired vasodilation in systemic and renal vessels. Salt-induced impairment of vasodilation occurred as early as 3 days after HSD, which preceded the onset of SS hypertension. Notably, the overt salt-induced hypertension in S-P467L mice was not driven by higher cardiac output, implying elevations in peripheral vascular resistance. In keeping with this, HSD-fed S-P467L mice exhibited decreased smooth muscle responsiveness to nitric oxide (NO) in systemic vessels. HSD-fed S-P467L mice also exhibited elevated albuminuria and a blunted increase in urinary NO metabolites which was associated with blunted renal blood flow and increased sodium retention mediated by a lack of HSD-induced suppression of NKCC2. Blocking NKCC2 function prevented the salt-induced increase in blood pressure in S-P467L mice. Conclusion We conclude that failure to vasodilate in response to salt loading causes SS hypertension by restricting renal perfusion and reducing renal NO through a mechanism involving NKCC2 in a mouse model of vascular peroxisome proliferator-activated receptor γ impairment.

Flow-mediated vasodilation is impaired in adult rat offspring exposed to prenatal hypoxia

2011 ◽  
Vol 110 (4) ◽  
pp. 1073-1082 ◽  
Author(s):  
J. S. Morton ◽  
C. F. Rueda-Clausen ◽  
S. T. Davidge
Keyword(s):  
Cardiovascular Diseases ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Female Offspring ◽  
Mesenteric Arteries ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Adult Rat ◽  
Increased Risk ◽  
The Impact

There is now a demonstrated association between low birth weight and increased mortality later in life. Changes in fetal development may program the cardiovascular system and lead to an increased risk of cardiovascular diseases later in life. In addition, aging is a risk factor for vascular endothelial-dependent dysfunction. However, the impact of being born intrauterine growth restricted (IUGR) on the normal aging mechanisms of vascular dysfunction is not clear. We hypothesized that IUGR would cause changes in vascular function that would affect the mechanisms of flow-induced vasodilation later in life in an age- or sex-dependent manner. To create an IUGR model, pregnant Sprague-Dawley rats were placed in a hypoxic (11.5% O2) or control (room air, 21% O2) environment from days 15 to 21 of pregnancy. Both male and female offspring were investigated at 4 or 12 mo of age. Vascular function was assessed in small mesenteric arteries using flow-induced vasodilation, a physiological stimuli of vasodilation, in a pressure myograph. Flow-induced vasodilation was unaffected at a young age, but was significantly reduced in aging IUGR compared with aging controls ( P < 0.05). Underlying vasodilator mechanisms were altered such that nitric oxide-mediated vasodilation was abolished in both young adult and aging IUGR males and females and in aging control females ( P > 0.05). Endothelium-derived hyperpolarizing factor-mediated vasodilation was maintained in all groups ( P < 0.01). A change in the mechanisms of vasodilation occurring at an earlier age in IUGR offspring may predispose them to develop cardiovascular diseases as an aging adult.

scholarly journals The impact of milk proteins and peptides on blood pressure and vascular function: a review of evidence from human intervention studies

2013 ◽  
Vol 26 (2) ◽  
pp. 177-190 ◽  
Author(s):  
Ágnes A. Fekete ◽  
D. Ian Givens ◽  
Julie A. Lovegrove
Keyword(s):  
Blood Pressure ◽  
Risk Factor ◽  
Whey Protein ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Milk Proteins ◽  
Vascular Health ◽  
Human Trials ◽  
The Impact ◽  
Proteins And Peptides

CVD are the leading cause of death worldwide. Hypertension, a major controllable risk factor of CVD, is intimately associated with vascular dysfunction, a defect which is also now recognised to be a major, modifiable risk factor for the development of CVD. The purpose of the present review was to critically evaluate the evidence for the effects of milk proteins and their associated peptides on blood pressure (BP) and vascular dysfunction. After a detailed literature search, the number of human trials evaluating the antihypertensive effects of casein-derived peptides (excluding isoleucine-proline-proline and valine-proline-proline) was found to be limited; the studies were preliminary with substantial methodological limitations. Likewise, the data from human trials that examined the effects of whey protein and peptides were also scarce and inconsistent. To date, only one study has conducted a comparative investigation on the relative effects of the two main intact milk proteins on BP and vascular function. While both milk proteins were shown to reduce BP, only whey protein improved measures of arterial stiffness. In contrast, a growing number of human trials have produced evidence to support beneficial effects of both milk proteins and peptides on vascular health. However, comparison of the relative outcomes from these trials is difficult owing to variation in the forms of assessment and measures of vascular function. In conclusion, there is an accumulating body of evidence to support positive effects of milk proteins in improving and/or maintaining cardiovascular health. However, the variable quality of the studies that produced this evidence, and the lack of robust, randomised controlled intervention trials, undermines the formulation of firm conclusions on the potential benefits of milk proteins and peptides on vascular health.

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