P6278Ageing is associated with increased endothelial sodium-glucose cotransporter 1 expression at arterial sites at risk promoting enhanced anthocyanin accumulation and improved vascular oxidative stress

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A B Chaker ◽  
P Algara-Suarez ◽  
L Remila ◽  
C Bruckert ◽  
S H Park ◽  
...  

Abstract Introduction Ageing is characterized by endothelial dysfunction and vascular oxidative stress affecting initially arterial sites at risk. Anthocyanin-rich products are potent stimulators of the endothelial formation of nitric oxide. Sodium-glucose co-transporter 1 (SGLT1) expression has been shown to be increased by oxidative stress and mediate anthocyanin uptake in endothelial cells. Purpose The study determined whether ageing is associated with an upregulation of SGLT1 in arterio-susceptible (aortic arch) and resistant (aorta) sites, and evaluated the vascular SGLT1-mediated anthocyanin uptake. In addition, the impact of a 2-week ingestion of an anthocyanin-rich blackcurrant concentrate (ARBC) by old rats on vascular anthocyanin uptake and oxidative stress, and systolic blood pressure (SBP) was assessed. Methods Male Wistar rats (22-month old) were either untreated or treated with ARBC (60 and 120 mg/kg/day) in the drinking water for 2 weeks. SGLT1 expression was assessed by immunofluorescence, anthocyanin accumulation by Neu A reagent using a purified extract (BCE) prepared from ARBC, oxidative stress by dihydroethidium using confocal microscopy, and SBP by tail-cuff sphingomanometry. Results SGLT1 immunofluorescence was observed predominantly in the endothelium and was higher in the aortic arch than the aorta in old rats whereas only low levels were observed in young rats (12-week old). Exposure of vascular sections to BCE resulted in anthocyanin uptake exclusively in the endothelium, which was higher in the aortic arch than the aorta, and more pronounced in old than young rats. Anthocyanin uptake induced by BCE in the aorta was markedly reduced by LX4211 (a SGLT1/2 inhibitor) both in old and young rats. A high level of oxidative stress was observed throughout the aortic wall of old compared to young rats, which was inhibited by LX4211. Ingestion of ARBC by old rats resulted in a dose-dependent accumulation of anthocyanins throughout the aorta wall and the aortic arch. The tissue accumulation of anthocyanins was associated with a reduced level of oxidative stress. Ageing was associated with increased SBP by about 8 mmHg, which was reduced by ARBC 60 and 120 mg/kg/day treatment by about 5 and 7 mmHg, respectively. Conclusion The present findings indicate that ageing is associated with an upregulation of SGLT1 predominantly in the endothelium and that this effect is more pronounced at the aortic arch than the aorta. The increased endothelial expression level of SGLT1 promoted a greater accumulation of anthocyanins sensitive to LX4211. In addition, a 2-week ingestion of ARBC by old rats resulted in the accumulation of anthocyanins throughout the arterial wall of the aortic arch and aorta, and resulted in a reduced level of oxidative stress and systolic blood pressure. Thus, SGLT1 may be an attractive target to restore vascular protection at arterial sites at risk by promoting endothelial and vascular uptake of anthocyanins.

2009 ◽  
Vol 2 (3) ◽  
pp. 138-145 ◽  
Author(s):  
Pedro Gomes ◽  
Sónia Simão ◽  
Elisabete Silva ◽  
Vanda Pinto ◽  
João S. Amaral ◽  
...  

The aim of this study was to investigate whether the effects of aging on oxidative stress markers and expression of major oxidant and antioxidant enzymes associate with impairment of renal function and increases in blood pressure. To explore this, we determined age-associated changes in lipid peroxidation (urinary malondialdehyde), plasma and urinary hydrogen peroxide (H2O2) levels, as well as renal H2O2production, and the expression of oxidant and antioxidant enzymes in young (13 weeks) and old (52 weeks) male Wistar Kyoto (WKY) rats. Urinary lipid peroxidation levels and H2O2production by the renal cortex and medulla of old rats were higher than their young counterparts. This was accompanied by overexpression of NADPH oxidase components Nox4 and p22phoxin the renal cortex of old rats. Similarly, expression of superoxide dismutase (SOD) isoforms 2 and 3 and catalase were increased in the renal cortex from old rats. Renal function parameters (creatinine clearance and fractional excretion of sodium), diastolic blood pressure and heart rate were not affected by aging, although slight increases in systolic blood pressure were observed during this 52-week period. It is concluded that overexpression of renal Nox4 and p22phoxand the increases in renal H2O2levels in aged WKY does not associate with renal functional impairment or marked increases in blood pressure. It is hypothesized that lack of oxidative stress-associated effects in aged WKY rats may result from increases in antioxidant defenses that counteract the damaging effects of H2O2.


2004 ◽  
Vol 82 (3) ◽  
pp. 200-207 ◽  
Author(s):  
R Tatchum-Talom ◽  
D S Martin

Ageing is associated with structural and functional alterations of the vasculature. The nature of age-related vascular disorders is not completely understood. Oxidative stress is hypothesized to play a crucial role in the pathophysiology of vascular complications. We investigated the effects of chronic treatment with the superoxide dismutase mimetic tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl) on vascular function in the mesenteric vasculature of aged rats. Young (3 weeks) and old (40 weeks) Sprague–Dawley rats were treated with tempol (1 mM in drinking water) or vehicle for 3 weeks. Arterial blood pressure was slightly, but significantly, higher in old than in young rats. Tempol had no effect on arterial blood pressure. The vasoconstrictor responses to norepinephrine (NE) and serotonin (5-HT) were exaggerated in the mesenteric vascular bed (MVB) removed from old rats. Vasodilator responses to acetylcholine (ACh), papaverine (PPV), and isoprenaline (ISO) were reduced in the MVB of old rats in comparison with young rats. Chronic treatment of old rats with tempol normalized their responses to NE and 5-HT. The dilator responses to ACh, PPV, and ISO were similar between old rats receiving tempol and young rats. The present findings suggest that oxidative stress contributes to vascular dysfunction in the mesentery of old rats. The vasculoprotective effects of tempol remain to be elucidated.Key words: ageing, oxidative stress, vascular reactivity.


2007 ◽  
Vol 292 (2) ◽  
pp. F861-F867 ◽  
Author(s):  
Melvin R. Hayden ◽  
Nazif A. Chowdhury ◽  
Shawna A. Cooper ◽  
Adam Whaley-Connell ◽  
Javad Habibi ◽  
...  

TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for the reabsorption of 5–8 g of glomerular filtered albumin each day. Excess filtered albumin may contribute to PTC damage and tubulointerstitial disease. This investigation examined the role of ANG II-induced oxidative stress in PTC structural remodeling: whether such changes could be modified with in vivo treatment with ANG type 1 receptor (AT1R) blockade (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6–7 wk old) and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-β-d-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and ×60,000 transmission electron microscopy images were used to assess PTC microvilli structure. There were significant differences in systolic blood pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean diameter of PTC microvilli in the placebo-treated Ren2 rats ( P < 0.05) correlated strongly with albuminuria ( r2 = 0.83) and moderately with MDA ( r2 = 0.49), and there was an increase in the ratio of abnormal forms of microvilli in placebo-treated Ren2 rats compared with Sprague-Dawley control rats ( P < 0.05). AT1R blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-β-d-glucosaminidase; both therapies corrected abnormalities in oxidative stress and PTC microvilli remodeling. These data indicate that PTC structural damage in the Ren2 rat is related to the oxidative stress response to ANG II and/or albuminuria.


2021 ◽  
Author(s):  
Sophie Jacqueline Andree Betka ◽  
David Watson ◽  
Sarah N Garfinkel ◽  
Gaby Pfeifer ◽  
Henrique Sequeira ◽  
...  

Objective: Emotional states are expressed in body and mind through subjective experience of physiological changes. In previous work, subliminal priming of anger prior to lexical decisions increased systolic blood pressure (SBP). This increase predicted the slowing of response times (RT), suggesting that baroreflex-related autonomic changes and their interoceptive (feedback) representations, influence cognition. Alexithymia is a subclinical affective dysfunction characterized by difficulty in identifying emotions. Atypical autonomic and interoceptive profiles are observed in alexithymia. Therefore, we sought to identify mechanisms through which SBP fluctuations during emotional processing might influence decision-making, including whether alexithymia contributes to this relationship. Methods Thirty-two male participants performed an affect priming paradigm and completed the Toronto Alexithymia Scale. Emotional faces were briefly presented (20ms) prior a short-term memory task. RT, accuracy and SBP were recorded on a trial-by-trial basis. Generalized mixed-effects linear models were used to evaluate the impact of emotion, physiological changes, alexithymia score, and their interactions, on performances. Results A main effect of emotion was observed on accuracy. Participants were more accurate on trials with anger primes, compared to neutral priming. Greater accuracy was related to increased SBP. An interaction between SBP and emotion was observed on RT: Increased SBP was associated with RT prolongation in the anger priming condition, yet this relationship was absent under the sadness priming. Alexithymia did not significantly moderate the above relationships. Conclusions Our data suggest that peripheral autonomic responses during affective challenges guide cognitive processes. We discuss our findings in the theoretical framework proposed by Lacey and Lacey (1970).


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Melissa S Burroughs Pena ◽  
Karina Romero ◽  
Antonio Bernabe Ortiz ◽  
Eric J Velazquez ◽  
J. Jaime Miranda ◽  
...  

Background: Household air pollution from biomass fuel use affects 3 billion people worldwide. There are few studies that examine the relationship between biomass fuel use and blood pressure. We sought to determine if daily biomass fuel use was associated with higher blood pressure and increased hypertension in Peru. Methods: We analyzed baseline information from an age- and sex-matched, population-based study in Puno, Peru. Daily biomass fuel use was self-reported. Hypertension was defined as a systolic blood pressure (SBP) ≥140 mmHg; diastolic blood pressure (DBP) ≥90 mmHg; or self-report of diagnosis and anti-hypertensive medications. We used linear and logistic multivariable regressions, adjusting for age, sex, daily cigarette use and body mass index, to examine the relationship between daily biomass fuel use with blood pressure and hypertension, respectively. Results: Data from 1004 individuals (mean age 55.3 years, 51.7% female) were included. There was evidence of an association between daily biomass fuel use and hypertension (adjusted OR = 2.1, 95%CI 1.2 to 3.5). Subjects who reported daily use of biomass fuels had 6.0 mmHg (95% CI 4.1 to 8.0) higher SBP and 4.8 mmHg (95%CI 3.5 to 6.0) higher DBP compared to those who did not use biomass fuels daily. In a secondary analysis, we used rural residence (vs. urban) as a proxy of biomass daily use and the relationship with hypertension and systolic blood pressure was similar: a higher odds of hypertension (adjusted OR = 2.1, 95%CI 1.3 to 3.6), and higher SBP (6.7mmHg, 95% CI 4.8 to 8.6) and DBP (5.5 mmHg, 95% CI 4.3 to 6.8) in rural vs. urban participants. Conclusion: Biomass fuel use is associated with increased odds of hypertension and higher blood pressure in Puno, Peru. Reducing exposure to air pollution from biomass fuel use represents a potential opportunity for cardiovascular prevention in rural communities worldwide. Longitudinal studies to evaluate the impact of reducing household air pollution are needed.


2019 ◽  
Vol 28 (3) ◽  
pp. 145-152
Author(s):  
E. G. Warmerdam ◽  
G. J. Krings ◽  
T. A. Meijs ◽  
A. C. Franken ◽  
B. W. Driesen ◽  
...  

Abstract Background Despite a successful repair procedure for coarctation of the aorta (CoA), up to two-thirds of patients remain hypertensive. CoA is often seen in combination with abnormal aortic arch anatomy and morphology. This might be a substrate for persistent hypertension. Therefore, we performed endovascular aortic arch stent placement in patients with CoA and concomitant aortic arch hypoplasia or gothic arch morphology. The goal of this retrospective analysis was to investigate the safety and efficacy of aortic arch stenting. Methods A retrospective analysis was performed in patients who underwent stenting of the aortic arch at the University Medical Center Utrecht. Measurements collected included office blood pressure, use of antihypertensive medication, invasive peak-to-peak systolic pressure over the arch, and aortic diameters on three-dimensional angiography. Data on follow-up were obtained at the date of most recent outpatient visit. Results Twelve patients underwent stenting of the aortic arch. Mean follow-up duration was 14 ± 11 months. Mean peak-to-peak gradient across the arch decreased from 39 ± 13 mm Hg to 7 ± 8 mm Hg directly after stenting (p < 0.001). There were no major procedural complications. Mean systolic blood pressure decreased from 145 ± 16 mm Hg at baseline to 128 ± 9 mm Hg at latest follow-up (p = 0.014). Conclusion This retrospective study shows that stenting of the aortic arch is successful when carried out in a state-of-the-art manner. A direct optimal angiographic and haemodynamic result was shown. No major complications occurred during or after the procedure. At short- to medium-term follow-up a decrease in mean systolic blood pressure was observed.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Aleksandr D. Vakhrushev ◽  
Heber Ivan Condori Leandro ◽  
Natalia S. Goncharova ◽  
Lev E. Korobchenko ◽  
Lubov B. Mitrofanova ◽  
...  

Objectives. We sought to assess acute changes in systemic and pulmonary hemodynamics and microscopic artery lesions following extended renal artery denervation (RDN). Background. RDN has been proposed to reduce sympathetic nervous system hyperactivation. Although the effects of RDN on systemic circulation and overall sympathetic activity have been studied, data on the impact of RDN on pulmonary hemodynamics is lacking. Methods. The study comprised 13 normotensive Landrace pigs. After randomization, 7 animals were allocated to the group of bilateral RDN and 6 animals to the group of a sham procedure (SHAM). Hemodynamic measures, cannulation, and balloon-based occlusion of the renal arteries were performed in both groups. In the RDN group, radiofrequency ablation was performed in all available arteries and their segments. An autopsy study of the renal arteries was carried out in both groups. Results. The analysis was performed on 12 pigs (6 in either group) since pulmonary thromboembolism occurred in one case. A statistically significant drop in the mean diastolic pulmonary artery pressure (PAP) was detected in the RDN group when compared with the SHAM group (change by 13.0 ± 4.4 and 10.0 ± 3.0   mmHg , correspondingly; P = 0.04 ). In 5 out of 6 pigs in the RDN group, a significant decrease in systemic systolic blood pressure was found, when compared with baseline ( 98.8 ± 17.8 vs. 90.2 ± 12.6   mmHg , P = 0.04 ), and a lower mean pulmonary vascular resistance (PVR) ( 291.0 ± 77.4 vs. 228.5 ± 63.8   dyn ∗ sec ∗ c m − 5 , P = 0.03 ) after ablation was found. Artery dissections were found in both groups, with prevalence in animals after RDN. Conclusions. Extensive RDN leads to a rapid and significant decrease in PAP. In the majority of cases, RDN is associated with an acute lowering of systolic blood pressure and PVR. Extended RDN is associated with artery wall lesions and thrombus formation underdiagnosed by angiography.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Huang ◽  
K Trieu ◽  
S Yoshimura ◽  
M Woodward ◽  
N Campbell ◽  
...  

Abstract Background Authoritative medical and public health agencies in most countries advise to reduce population dietary salt intake to under 5–6 g/day as a strategy for preventing high blood pressure and cardiovascular disease. However, there is still dispute about whether salt reduction should be adopted by all populations. In addition, the effect of duration of dietary salt reduction has not been sufficiently investigated. Purpose To understand the effect of dietary salt reduction on blood pressure and the impact of intervention duration. Methods A systematic review and meta-analysis was conducted. Randomized controlled trials that allocated participants to low and high salt intake, without confounding from unequal concomitant interventions, were included. We excluded studies done in individuals younger than 18 years, pregnant women, individuals with renal disease or heart failure, and studies with sodium excretion estimated from spot urine. Random effect meta-analysis was used to generate pooled estimates of the effect on 24-hour urinary sodium excretion, systolic and diastolic blood pressure. Multivariate meta-regression was used to quantify the dose response effect of dietary salt on blood pressure change and to understand the impact of the intervention duration. Results 125 studies were included with 162 data points extracted. Ninety-nine data points (61%) had interventions under 4 weeks. Overall, 24-hour urinary sodium excretion changed by −141 mmol (95% CI: −156; −126), systolic blood pressure changed by −4.4 mm Hg (95% CI: −5.2; −3.7) and diastolic blood pressure changed by −2.4 mm Hg (95% CI: −2.9; −1.9). Sodium reduction resulted in a significant decrease of systolic blood pressure in all subgroups except in participants with low baseline sodium intake (<109 mmol) (Figure 1). Each 100 mmol reduction of sodium was associated with 2.7 mm Hg (95% CI: 1.0; 4.4; p=0.002) reduction of systolic blood pressure and 1.2 mm Hg (95% CI: 0.0; 2.4; p=0.046) reduction of diastolic blood pressure after adjusting for intervention duration, age, sex, race, baseline blood pressure, baseline sodium intake and interaction between age and baseline blood pressure. For the same amount of salt reduction, a 10 mm Hg higher baseline systolic blood pressure would result in 2.5 mm Hg greater reduction of systolic blood pressure. There is not enough evidence to show the impact of intervention duration. Figure 1 Conclusions Our meta-analysis showed that sodium reduction could reduce blood pressure in all adult populations regardless of age, sex and race. The effect of salt reduction on systolic blood pressure increases with higher baseline blood pressure. Further studies, designed to investigate the impact of intervention duration, are needed to understand the significance of the duration. Acknowledgement/Funding None


2008 ◽  
Vol 295 (2) ◽  
pp. R543-R549 ◽  
Author(s):  
Analía Lorena Tomat ◽  
Felipe Inserra ◽  
Luciana Veiras ◽  
María Constanza Vallone ◽  
Ana María Balaszczuk ◽  
...  

Intrauterine and postnatal zinc restriction may result in an adverse environment for the development of cardiovascular and renal systems. This study evaluated the effects of moderate zinc deficiency during fetal life, lactation, and/or postweaning growth on systolic blood pressure, renal function, and morphology in adult life. Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy up to weaning. After weaning, male offspring of each group of mothers were fed low or control zinc diet. Systolic blood pressure, creatinine clearance, proteinuria, renal morphology, renal apoptosis. and renal oxidative stress state were evaluated after 60 days. Zinc deficiency during pre- and postweaning growth induced an increase in systolic blood pressure and a decrease in the glomerular filtration rate associated with a reduction in the number and size of nephrons. Activation of renal apoptosis, reduction in catalase activity, glutathione peroxidase activity, and glutathione levels and increase in lipid peroxidation end products could explain these morphometric changes. Zinc deficiency through pre- and postweaning growth induced more pronounced renal alteration than postweaning zinc deficiency. These animals showed signs of renal fibrosis, proteinuria, increased renal apoptosis, and higher lipid peroxidation end products. A control diet during postweaning growth did not totally overcome renal oxidative stress damage, apoptosis, and fibrosis induced by zinc deficiency before weaning. In conclusion, zinc deficiency during a critical period of renal development and maturation could induce functional and morphological alterations that result in elevated blood pressure and renal dysfunction in adult life.


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