Ascorbic acid increases cardiovagal baroreflex sensitivity in healthy older men

2004 ◽  
Vol 286 (6) ◽  
pp. H2113-H2117 ◽  
Author(s):  
Kevin D. Monahan ◽  
Iratxe Eskurza ◽  
Douglas R. Seals

Cardiovagal baroreflex sensitivity (BRS) declines with advancing age in healthy men. We tested the hypothesis that oxidative stress contributes mechanistically to this age-associated reduction. Eight young (23 ± 1 yrs, means ± SE) and seven older (63 ± 3) healthy men were studied. Cardiovagal BRS was assessed using the modified Oxford technique (bolus infusion of 50–100 μg sodium nitroprusside, followed 60 s later by a 100- to 150-μg bolus of phenylephrine hydrochloride) in triplicate at baseline and during acute intravenous ascorbic acid infusion. At baseline, cardiovagal BRS (slope of the linear portion of the R-R interval-systolic blood pressure relation during pharmacological changes in arterial blood pressure) was 56% lower ( P < 0.01) in older (8.3 ± 1.6 ms/mmHg) compared with young (19.0 ± 3.1 ms/mmHg) men. Ascorbic acid infusion increased plasma concentrations similarly in young (62 ± 9 vs. 1,249 ± 72 μmol/l for baseline and during ascorbic acid; P < 0.05) and older men (62 ± 4 vs. 1,022 ± 55 μmol/l; P < 0.05) without affecting baseline blood pressure, heart rate, carotid artery compliance, or the magnitude of change in systolic blood pressure in response to bolus sodium nitroprusside and phenylephrine hydrochloride infusion. Ascorbic acid (vitamin C) infusion increased cardiovagal BRS in older (Δ58 ± 16%; P < 0.01), but not younger (Δ − 4 ± 4%) men. These data provide experimental support for the concept that oxidative stress contributes mechanistically to age-associated reductions in cardiovagal BRS in healthy men.

2004 ◽  
Vol 286 (4) ◽  
pp. H1528-H1534 ◽  
Author(s):  
Iratxe Eskurza ◽  
Kevin D. Monahan ◽  
Jed A. Robinson ◽  
Douglas R. Seals

Large elastic artery compliance is reduced and arterial blood pressure (BP) is increased in the central (cardiothoracic) circulation with aging. Reactive oxygen species may tonically modulate central arterial compliance and BP in humans, and oxidative stress may contribute to adverse changes with aging. If so, antioxidant administration may have beneficial effects. Young (Y; 26 ± 1 yr, mean ± SE) and older (O; 63 ± 2 yr, mean ± SE) healthy men were studied at baseline and during acute (intravenous infusion; Y: n = 13, O: n = 12) and chronic (500 mg/day for 30 days; Y: n = 10, O: n = 10) administration of ascorbic acid (vitamin C). At baseline, peripheral (brachial artery) BP did not differ in the two groups, but carotid artery compliance was 43% lower (1.2 ± 0.1 vs. 2.1 ± 0.1 mm2/mmHg × 10–1, P < 0.01) and central (carotid) BP (systolic: 116 ± 5 vs. 101 ± 3 mmHg, P < 0.05, and pulse pressure: 43 ± 4 vs. 36 ± 3 mmHg, P = 0.16), carotid augmentation index (AIx; 27.8 ± 7.8 vs. –20.0 ± 6.6%, P < 0.001), and aortic pulse wave velocity (PWV; 950 ± 88 vs. 640 ± 38 cm/s, P < 0.01) were higher in the older men. Plasma ascorbic acid concentrations did not differ at baseline (Y: 71 ± 5 vs. O: 61 ± 7 μmol/l, P = 0.23), increased ( P < 0.001) to supraphysiological levels during infusion (Y: 1,240 ± 57 and O: 1,056 ± 83 μmol/l), and were slightly elevated ( P < 0.001 vs. baseline) with supplementation (Y: 96 ± 5 μmol/l vs. O: 85 ± 6). Neither ascorbic acid infusion nor supplementation affected peripheral BP, heart rate, carotid artery compliance, central BP, carotid AIx, or aortic PWV (all P > 0.26). These results indicate that the adverse changes in large elastic artery compliance and central BP with aging in healthy men are not 1) mediated by ascorbic acid-sensitive oxidative stress (infusion experiments) and 2) affected by short-term, moderate daily ascorbic acid (vitamin C) supplementation.


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.


1999 ◽  
Vol 47 (12) ◽  
pp. 1415-1421 ◽  
Author(s):  
Kiyohito Okumiya ◽  
Kozo Matsubayashi ◽  
Tomoko Wada ◽  
Michiko Fujisawa ◽  
Yasushi Osaki ◽  
...  

2008 ◽  
Vol 295 (3) ◽  
pp. H1150-H1155 ◽  
Author(s):  
François Cottin ◽  
Claire Médigue ◽  
Yves Papelier

The aim of the study was to assess the instantaneous spectral components of heart rate variability (HRV) and systolic blood pressure variability (SBPV) and determine the low-frequency (LF) and high-frequency baroreflex sensitivity (HF-BRS) during a graded maximal exercise test. The first hypothesis was that the hyperpnea elicited by heavy exercise could entail a significant increase in HF-SBPV by mechanical effect once the first and second ventilatory thresholds (VTs) were exceeded. It was secondly hypothesized that vagal tone progressively withdrawing with increasing load, HF-BRS could decrease during the exercise test. Fifteen well-trained subjects participated in this study. Electrocardiogram (ECG), blood pressure, and gas exchanges were recorded during a cycloergometer test. Ventilatory equivalents were computed from gas exchange parameters to assess VTs. Spectral analysis was applied on cardiovascular series to compute RR and systolic blood pressure power spectral densities, cross-spectral coherence, gain, and α index of BRS. Three exercise intensity stages were compared: below (A1), between (A2), and above (A3) VTs. From A1 to A3, both HF-SBPV (A1: 45 ± 6, A2: 65 ± 10, and A3: 120 ± 23 mm2Hg, P < 0.001) and HF-HRV increased (A1: 20 ± 5, A2: 23 ± 8, and A3:40 ± 11 ms2, P < 0.02), maintaining HF-BRS (gain, A1: 0.68 ± 0.12, A2: 0.63 ± 0.08, and A3: 0.57 ± 0.09; α index, A1: 0.58 ± 0.08, A2: 0.48 ± 0.06, and A3: 0.50 ± 0.09 ms/mmHg, not significant). However, LF-BRS decreased (gain, A1: 0.39 ± 0.06, A2: 0.17 ± 0.02, and A3: 0.11 ± 0.01, P < 0.001; α index, A1: 0.46 ± 0.07, A2: 0.20 ± 0.02, and A3: 0.14 ± 0.01 ms/mmHg, P < 0.001). As expected, once VTs were exceeded, hyperpnea induced a marked increase in both HF-HRV and HF-SBPV. However, this concomitant increase allowed the maintenance of HF-BRS, presumably by a mechanoelectric feedback mechanism.


Hypertension ◽  
2020 ◽  
Vol 75 (1) ◽  
pp. 44-50 ◽  
Author(s):  
Julian E. Mariampillai ◽  
Knut Liestøl ◽  
Sverre E. Kjeldsen ◽  
Erik E. Prestgaard ◽  
Kristian Engeseth ◽  
...  

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.


2001 ◽  
Vol 21 (1) ◽  
pp. 82-87 ◽  
Author(s):  
Hirofumi Tanaka ◽  
Frank A. Dinenno ◽  
Kevin D. Monahan ◽  
Christopher A. DeSouza ◽  
Douglas R. Seals

1982 ◽  
Vol 63 (s8) ◽  
pp. 411s-414s ◽  
Author(s):  
Jun Ogawa ◽  
Shigeo Takata ◽  
Gakuji Nomura ◽  
Shiro Arai ◽  
Takayuki Ikeda ◽  
...  

1. We studied the effects of aging on the variability of blood pressure in mild to moderate essential hypertensive subjects. 2. Cardiac index was greater and total peripheral resistance index was less in patients under 40 years (by an average of 1.06 litres min−1 m−2 and 9.23 mmHg 1−1 min−1 m−2) than in those over 40 respectively (P < 0.001 for each). 3. Pulse pressure/stroke volume was less by an average of 0.345 mmHg/ml in patients under 40 years than that in those over 40 (P < 0.001). Pulse pressure/stroke volume was correlated with age (r = 0.621), average systolic blood pressure (r = 0.623) and inversely with baroreflex sensitivity (r = −0.494). 4. Baroreflex sensitivity was less by an average of 3.1 ms/mmHg in patients over 30 years than in those under 30 (P < 0.025). Baroreflex sensitivity was inversely correlated with age (r = −0.617) and average systolic blood pressure (r = −0.589). 5. Beat by beat variability of systolic blood pressure was correlated with age (r = 0.460), particularly when the data of those in their twenties were excluded (r = 0.618), and significantly with pulse pressure/stroke volume (r = 0.650), average systolic blood pressure (r = 0.618) and inversely with baroreflex sensitivity (r = −0.477). These relationships were not observed for diastolic blood pressure. 6. Maximum difference in systolic blood pressure in a day was correlated with pulse pressure/stroke volume (r = 0.482) and average systolic blood pressure (r = 0.648) but not with baroreflex sensitivity. These relationships were not observed for diastolic blood pressure. 7. Variability of systolic blood pressure in patients over 30 years gradually increased with age. In contrast, those of systolic and diastolic blood pressures in subjects in their twenties were relatively large. This might be related to factors other than aging, presumably those which underlie the hyperdynamic circulatory state.


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.


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