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Douglas R Seals - One of the best experts on this subject based on the ideXlab platform.

  • oral trehalose supplementation improves resistance Artery endothelial function in healthy middle aged and older adults
    Aging (Albany NY), 2016
    Co-Authors: Rachelle E Kaplon, Molly J Nowlan, Sierra D Hill, Nina Z Bispham, Jessica R Santosparker, Laura L Snyder, Michel Chonchol, Thomas J Larocca, Matthew B Mcqueen, Douglas R Seals
    Abstract:

    We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose (n=15) or maltose (n=17, isocaloric control) for 12 weeks (randomized, double-blind). In subjects with Δbody mass less than 2.3kg (5 lb.), resistance Artery endothelial function, assessed by forearm blood flow to brachial Artery infusion of acetylcholine (FBFACh), increased ~30% with trehalose (13.3±1.0 vs. 10.5±1.1 AUC, P=0.02), but not maltose (P=0.40). This improvement in FBFACh was abolished when endothelial nitric oxide (NO) production was inhibited. Endothelium-independent dilation, assessed by FBF to sodium nitroprusside (FBFSNP), also increased ~30% with trehalose (155±13 vs. 116±12 AUC, P=0.03) but not maltose (P=0.92). Changes in FBFACh and FBFSNP with trehalose were not significant when subjects with Δbody mass ≥ 2.3kg were included. Trehalose supplementation had no effect on conduit Artery endothelial function, large Elastic Artery stiffness or circulating markers of oxidative stress or inflammation (all P>0.1) independent of changes in body weight. Our findings demonstrate that oral trehalose improves resistance Artery (microvascular) function, a major risk factor for cardiovascular diseases, in MA/O adults, possibly through increasing NO bioavailability and smooth muscle sensitivity to NO.

  • nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice
    Aging Cell, 2016
    Co-Authors: Natalie De Picciotto, Amy L Sindler, Lindsey B Gano, Lawrence C Johnson, Shinichiro Imai, Christopher R Martens, Kathryn F Mills, Douglas R Seals
    Abstract:

    We tested the hypothesis that supplementation of nicotinamide mononucleotide (NMN), a key NAD + intermediate, increases arterial SIRT1 activity and reverses age‐associated arterial dysfunction and oxidative stress. Old control mice (OC) had impaired carotid Artery endothelium‐dependent dilation (EDD) (60 ± 5% vs. 84 ± 2%), a measure of endothelial function, and nitric oxide (NO)‐mediated EDD (37 ± 4% vs. 66 ± 6%), compared with young mice (YC). This age‐associated impairment in EDD was restored in OC by the superoxide (O2−) scavenger TEMPOL (82 ± 7%). OC also had increased aortic pulse wave velocity (aPWV, 464 ± 31 cm s−1 vs. 337 ± 3 cm s−1) and Elastic modulus (EM, 6407 ± 876 kPa vs. 3119 ± 471 kPa), measures of large Elastic Artery stiffness, compared with YC. OC had greater aortic O2− production (2.0 ± 0.1 vs. 1.0 ± 0.1 AU), nitrotyrosine abundance (a marker of oxidative stress), and collagen‐I, and reduced elastin and vascular SIRT1 activity, measured by the acetylation status of the p65 subunit of NFκB, compared with YC. Supplementation with NMN in old mice restored EDD (86 ± 2%) and NO‐mediated EDD (61 ± 5%), reduced aPWV (359 ± 14 cm s−1) and EM (3694 ± 315 kPa), normalized O2− production (0.9 ± 0.1 AU), decreased nitrotyrosine, reversed collagen‐I, increased elastin, and restored vascular SIRT1 activity. Acute NMN incubation in isolated aortas increased NAD + threefold and manganese superoxide dismutase (MnSOD) by 50%. NMN supplementation may represent a novel therapy to restore SIRT1 activity and reverse age‐related arterial dysfunction by decreasing oxidative stress.

  • reduced large Elastic Artery stiffness with regular aerobic exercise in middle aged and older adults potential role of suppressed nuclear factor κ b signalling
    Journal of Hypertension, 2015
    Co-Authors: Kristen L Jablonski, Bradley S Fleenor, Ashley E Walker, Anthony J Donato, Molly J Nowlan, Rachelle E Kaplon, Dov B Ballak, Douglas R Seals
    Abstract:

    OBJECTIVE Aortic pulse-wave velocity (aPWV) increases with age and is a strong independent predictor of incident cardiovascular diseases (CVDs) in healthy middle-aged and older adults. aPWV is lower in middle-aged and older adults who perform regular aerobic exercise than in their sedentary peers. As exercise is associated with reduced systemic inflammation, we hypothesized that suppression of the pro-inflammatory transcription factor nuclear factor κ B (NFκB) may mediate this process. METHODS aPWV was measured in young sedentary [n = 10, blood pressure (BP) 108 ± 3/59 ± 2 mmHg; mean ± SEM], middle-aged and older sedentary (n = 9, 124 ± 7/73 ± 5 mmHg) and middle-aged and older aerobic exercise-trained (n = 12, 110 ± 4/67 ± 2 mmHg) healthy, nonhypertensive men and women. RESULTS Baseline aPWV increased with age [626 ± 14 (young sedentary) vs. 859 ± 49 (middle-aged and older sedentary) cm/s, P < 0.001] but was 20% lower in middle-aged and older trained (686 ± 30 cm/s) than in middle-aged and older sedentary (P < 0.005). Short-term (4 days  x  2500-4500 mg) treatment with the NFκB inhibitor salsalate (randomized, placebo-controlled cross-over design) reduced aPWV (to 783 ± 44 cm/s, P < 0.05) without changing BP (P = 0.40) or heart rate (P = 0.90) in middle-aged and older sedentary, but had no effect in young sedentary (623 ± 19) or middle-aged and older trained (699 ± 30). Following salsalate treatment, aPWV no longer was significantly different in middle-aged and older sedentary vs. middle-aged and older trained (P = 0.29). The reduction in aPWV with salsalate administration was inversely related to baseline (placebo) aPWV (r = -0.60, P < 0.001). CONCLUSION These results support the hypothesis that suppressed NFκB signalling may partially mediate the lower aortic stiffness in middle-aged and older adults who regularly perform aerobic exercise. Because aPWV predicts incident cardiovascular events in this population, this suggests that tonic suppression of NFκB signalling in middle-aged and older exercising adults may potentially lower cardiovascular risk.

  • superoxide signaling in perivascular adipose tissue promotes age related Artery stiffness
    Aging Cell, 2014
    Co-Authors: Amy L Sindler, Bradley S Fleenor, Jason S Eng, Bryant Thanh Pham, Jackson Kloor, Douglas R Seals
    Abstract:

    We tested the hypothesis that superoxide signaling within aortic perivascular adipose tissue (PVAT) contributes to large Elastic Artery stiffening in old mice. Young (4–6 months), old (26–28 months), and old treated with 4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL), a superoxide scavenger (1 mm in drinking water for 3 weeks), male C57BL6/N mice were studied. Compared with young, old had greater large Artery stiffness assessed by aortic pulse wave velocity (aPWV, 436 ± 9 vs. 344 ± 5 cm s-1) and intrinsic mechanical testing (3821 ± 427 vs. 1925 ± 271 kPa) (both P < 0.05). TEMPOL treatment in old reversed both measures of arterial stiffness. Aortic PVAT superoxide production was greater in old (P < 0.05 vs. Y), which was normalized with TEMPOL. Compared with young, old controls had greater pro-inflammatory proteins in PVAT-conditioned media (P < 0.05). Young recipient mice transplanted with PVAT from old compared with young donors for 8 weeks had greater aPWV (409 ± 7 vs. 342 ± 8 cm s-1) and intrinsic mechanical properties (3197 ± 647 vs. 1889 ± 520 kPa) (both P < 0.05), which was abolished with TEMPOL supplementation in old donors. Tissue-cultured aortic segments from old in the presence of PVAT had greater mechanical stiffening compared with old cultured in the absence of PVAT and old with PVAT and TEMPOL (both, P < 0.05). In addition, PVAT-derived superoxide was associated with arterial wall hypertrophy and greater adventitial collagen I expression with aging that was attenuated by TEMPOL. Aging or TEMPOL treatment did not affect blood pressure. Our findings provide evidence for greater age-related superoxide production and pro-inflammatory proteins in PVAT, and directly link superoxide signaling in PVAT to large Elastic Artery stiffness.

  • nicotinamide mononucleotide supplementation reverses vascular endothelial dysfunction and large Elastic Artery stiffness in old mice 698 10
    The FASEB Journal, 2014
    Co-Authors: Natalie De Picciotto, Douglas R Seals, Lindsey B Gano, Lawrence C Johnson, Stewart Weber, Shinichiro Imai, K A Mills, Amy L Sindler
    Abstract:

    Reduced bioavailability of nicotinamide adenine dinucleotide (NAD+), a cofactor for the deacetylase sirtuin1 (SIRT1), may contribute to age-related vascular dysfunction via oxidative stress and red...

Amy L Sindler - One of the best experts on this subject based on the ideXlab platform.

  • nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice
    Aging Cell, 2016
    Co-Authors: Natalie De Picciotto, Amy L Sindler, Lindsey B Gano, Lawrence C Johnson, Shinichiro Imai, Christopher R Martens, Kathryn F Mills, Douglas R Seals
    Abstract:

    We tested the hypothesis that supplementation of nicotinamide mononucleotide (NMN), a key NAD + intermediate, increases arterial SIRT1 activity and reverses age‐associated arterial dysfunction and oxidative stress. Old control mice (OC) had impaired carotid Artery endothelium‐dependent dilation (EDD) (60 ± 5% vs. 84 ± 2%), a measure of endothelial function, and nitric oxide (NO)‐mediated EDD (37 ± 4% vs. 66 ± 6%), compared with young mice (YC). This age‐associated impairment in EDD was restored in OC by the superoxide (O2−) scavenger TEMPOL (82 ± 7%). OC also had increased aortic pulse wave velocity (aPWV, 464 ± 31 cm s−1 vs. 337 ± 3 cm s−1) and Elastic modulus (EM, 6407 ± 876 kPa vs. 3119 ± 471 kPa), measures of large Elastic Artery stiffness, compared with YC. OC had greater aortic O2− production (2.0 ± 0.1 vs. 1.0 ± 0.1 AU), nitrotyrosine abundance (a marker of oxidative stress), and collagen‐I, and reduced elastin and vascular SIRT1 activity, measured by the acetylation status of the p65 subunit of NFκB, compared with YC. Supplementation with NMN in old mice restored EDD (86 ± 2%) and NO‐mediated EDD (61 ± 5%), reduced aPWV (359 ± 14 cm s−1) and EM (3694 ± 315 kPa), normalized O2− production (0.9 ± 0.1 AU), decreased nitrotyrosine, reversed collagen‐I, increased elastin, and restored vascular SIRT1 activity. Acute NMN incubation in isolated aortas increased NAD + threefold and manganese superoxide dismutase (MnSOD) by 50%. NMN supplementation may represent a novel therapy to restore SIRT1 activity and reverse age‐related arterial dysfunction by decreasing oxidative stress.

  • superoxide signaling in perivascular adipose tissue promotes age related Artery stiffness
    Aging Cell, 2014
    Co-Authors: Amy L Sindler, Bradley S Fleenor, Jason S Eng, Bryant Thanh Pham, Jackson Kloor, Douglas R Seals
    Abstract:

    We tested the hypothesis that superoxide signaling within aortic perivascular adipose tissue (PVAT) contributes to large Elastic Artery stiffening in old mice. Young (4–6 months), old (26–28 months), and old treated with 4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL), a superoxide scavenger (1 mm in drinking water for 3 weeks), male C57BL6/N mice were studied. Compared with young, old had greater large Artery stiffness assessed by aortic pulse wave velocity (aPWV, 436 ± 9 vs. 344 ± 5 cm s-1) and intrinsic mechanical testing (3821 ± 427 vs. 1925 ± 271 kPa) (both P < 0.05). TEMPOL treatment in old reversed both measures of arterial stiffness. Aortic PVAT superoxide production was greater in old (P < 0.05 vs. Y), which was normalized with TEMPOL. Compared with young, old controls had greater pro-inflammatory proteins in PVAT-conditioned media (P < 0.05). Young recipient mice transplanted with PVAT from old compared with young donors for 8 weeks had greater aPWV (409 ± 7 vs. 342 ± 8 cm s-1) and intrinsic mechanical properties (3197 ± 647 vs. 1889 ± 520 kPa) (both P < 0.05), which was abolished with TEMPOL supplementation in old donors. Tissue-cultured aortic segments from old in the presence of PVAT had greater mechanical stiffening compared with old cultured in the absence of PVAT and old with PVAT and TEMPOL (both, P < 0.05). In addition, PVAT-derived superoxide was associated with arterial wall hypertrophy and greater adventitial collagen I expression with aging that was attenuated by TEMPOL. Aging or TEMPOL treatment did not affect blood pressure. Our findings provide evidence for greater age-related superoxide production and pro-inflammatory proteins in PVAT, and directly link superoxide signaling in PVAT to large Elastic Artery stiffness.

  • nicotinamide mononucleotide supplementation reverses vascular endothelial dysfunction and large Elastic Artery stiffness in old mice 698 10
    The FASEB Journal, 2014
    Co-Authors: Natalie De Picciotto, Douglas R Seals, Lindsey B Gano, Lawrence C Johnson, Stewart Weber, Shinichiro Imai, K A Mills, Amy L Sindler
    Abstract:

    Reduced bioavailability of nicotinamide adenine dinucleotide (NAD+), a cofactor for the deacetylase sirtuin1 (SIRT1), may contribute to age-related vascular dysfunction via oxidative stress and red...

  • sodium nitrite de stiffening of large Elastic arteries with aging role of normalization of advanced glycation end products
    Experimental Gerontology, 2012
    Co-Authors: Bradley S Fleenor, Amy L Sindler, Devatha P Nair, Blair R Dodson, Douglas R Seals
    Abstract:

    Abstract We tested the hypothesis that sodium nitrite treatment reverses large Elastic Artery stiffening in old mice via reductions in collagen I, increases in elastin and/or decreases in advanced glycation end products (AGEs) mediated by reduced oxidative stress. Aortic pulse wave velocity (aPWV), a measure of large Elastic Artery stiffness, was greater in old (26–28 months) compared with young (4–6 months) control animals (520 ± 9 vs. 405 ± 6 cm/s, p

  • superoxide lowering therapy with tempol reverses arterial dysfunction with aging in mice
    Aging Cell, 2012
    Co-Authors: Bradley S Fleenor, Melanie L Zigler, Douglas R Seals, Amy L Sindler
    Abstract:

    To test the hypothesis that the antioxidant enzyme superoxide dismutase (SOD) mimetic TEMPOL improves arterial aging, young (Y, 4–6 mo) and old (O, 26–28 mo) male C57BL6 mice received regular or TEMPOL-supplemented (1mM) drinking water for 3 weeks (n=8/group). Aortic superoxide was 65% greater in O (p<0.05 vs. Y), which was normalized by TEMPOL. O had large Elastic Artery stiffening, as indicated by greater aortic pulse wave velocity (aPWV, 508 ± 22 vs. 418 ± 22 AU), which was associated with increased adventitial collagen I expression (p<0.05 vs. Y). TEMPOL reversed the age-associated increases in aPWV (434 ± 21 AU) and collagen in vivo, and SOD reversed increases in collagen I in adventitial fibroblasts from older rats in vitro. Isolated carotid arteries of O had impaired endothelial function as indicated by reduced acetylcholine-stimulated endothelium-dependent dilation (EDD) (75.6 ± 3.2 vs. 94.5 ± 2.0%) mediated by reduced nitric oxide (NO) bioavailability (L-NAME) associated with decreased endothelial NO synthase (eNOS) expression (p<0.05 vs. Y). TEMPOL restored EDD (94.5 ± 1.4%), NO bioavailability and eNOS in O. Nitrotyrosine and expression of NADPH oxidase were ~100–200% greater, and MnSOD was ~75% lower in O (p<0.05 vs. Y). TEMPOL normalized nitrotyrosine and NADPH oxidase in O, without affecting MnSOD. Aortic pro-inflammatory cytokines were greater in O (p<0.05 vs. Y) and normalized by TEMPOL. Short-term treatment of excessive superoxide with TEMPOL ameliorates large Elastic Artery stiffening and endothelial dysfunction with aging, and this is associated with normalization of arterial collagen I, eNOS, oxidative stress and inflammation.

Bradley S Fleenor - One of the best experts on this subject based on the ideXlab platform.

  • reduced large Elastic Artery stiffness with regular aerobic exercise in middle aged and older adults potential role of suppressed nuclear factor κ b signalling
    Journal of Hypertension, 2015
    Co-Authors: Kristen L Jablonski, Bradley S Fleenor, Ashley E Walker, Anthony J Donato, Molly J Nowlan, Rachelle E Kaplon, Dov B Ballak, Douglas R Seals
    Abstract:

    OBJECTIVE Aortic pulse-wave velocity (aPWV) increases with age and is a strong independent predictor of incident cardiovascular diseases (CVDs) in healthy middle-aged and older adults. aPWV is lower in middle-aged and older adults who perform regular aerobic exercise than in their sedentary peers. As exercise is associated with reduced systemic inflammation, we hypothesized that suppression of the pro-inflammatory transcription factor nuclear factor κ B (NFκB) may mediate this process. METHODS aPWV was measured in young sedentary [n = 10, blood pressure (BP) 108 ± 3/59 ± 2 mmHg; mean ± SEM], middle-aged and older sedentary (n = 9, 124 ± 7/73 ± 5 mmHg) and middle-aged and older aerobic exercise-trained (n = 12, 110 ± 4/67 ± 2 mmHg) healthy, nonhypertensive men and women. RESULTS Baseline aPWV increased with age [626 ± 14 (young sedentary) vs. 859 ± 49 (middle-aged and older sedentary) cm/s, P < 0.001] but was 20% lower in middle-aged and older trained (686 ± 30 cm/s) than in middle-aged and older sedentary (P < 0.005). Short-term (4 days  x  2500-4500 mg) treatment with the NFκB inhibitor salsalate (randomized, placebo-controlled cross-over design) reduced aPWV (to 783 ± 44 cm/s, P < 0.05) without changing BP (P = 0.40) or heart rate (P = 0.90) in middle-aged and older sedentary, but had no effect in young sedentary (623 ± 19) or middle-aged and older trained (699 ± 30). Following salsalate treatment, aPWV no longer was significantly different in middle-aged and older sedentary vs. middle-aged and older trained (P = 0.29). The reduction in aPWV with salsalate administration was inversely related to baseline (placebo) aPWV (r = -0.60, P < 0.001). CONCLUSION These results support the hypothesis that suppressed NFκB signalling may partially mediate the lower aortic stiffness in middle-aged and older adults who regularly perform aerobic exercise. Because aPWV predicts incident cardiovascular events in this population, this suggests that tonic suppression of NFκB signalling in middle-aged and older exercising adults may potentially lower cardiovascular risk.

  • superoxide signaling in perivascular adipose tissue promotes age related Artery stiffness
    Aging Cell, 2014
    Co-Authors: Amy L Sindler, Bradley S Fleenor, Jason S Eng, Bryant Thanh Pham, Jackson Kloor, Douglas R Seals
    Abstract:

    We tested the hypothesis that superoxide signaling within aortic perivascular adipose tissue (PVAT) contributes to large Elastic Artery stiffening in old mice. Young (4–6 months), old (26–28 months), and old treated with 4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL), a superoxide scavenger (1 mm in drinking water for 3 weeks), male C57BL6/N mice were studied. Compared with young, old had greater large Artery stiffness assessed by aortic pulse wave velocity (aPWV, 436 ± 9 vs. 344 ± 5 cm s-1) and intrinsic mechanical testing (3821 ± 427 vs. 1925 ± 271 kPa) (both P < 0.05). TEMPOL treatment in old reversed both measures of arterial stiffness. Aortic PVAT superoxide production was greater in old (P < 0.05 vs. Y), which was normalized with TEMPOL. Compared with young, old controls had greater pro-inflammatory proteins in PVAT-conditioned media (P < 0.05). Young recipient mice transplanted with PVAT from old compared with young donors for 8 weeks had greater aPWV (409 ± 7 vs. 342 ± 8 cm s-1) and intrinsic mechanical properties (3197 ± 647 vs. 1889 ± 520 kPa) (both P < 0.05), which was abolished with TEMPOL supplementation in old donors. Tissue-cultured aortic segments from old in the presence of PVAT had greater mechanical stiffening compared with old cultured in the absence of PVAT and old with PVAT and TEMPOL (both, P < 0.05). In addition, PVAT-derived superoxide was associated with arterial wall hypertrophy and greater adventitial collagen I expression with aging that was attenuated by TEMPOL. Aging or TEMPOL treatment did not affect blood pressure. Our findings provide evidence for greater age-related superoxide production and pro-inflammatory proteins in PVAT, and directly link superoxide signaling in PVAT to large Elastic Artery stiffness.

  • large Elastic Artery stiffness with aging novel translational mechanisms and interventions
    Aging and Disease, 2013
    Co-Authors: Bradley S Fleenor
    Abstract:

    Large Elastic Artery stiffness is an independent predictor of age-related cardiovascular events that is attributable to structural remodeling throughout the Artery. The intima, media and adventitial layers of the Artery uniquely remodel with advancing age and all contribute to arterial stiffening. The specific expression of the extracellular matrix proteins collagen and elastin, and post-translational modifications of these proteins by advanced glycation end-products are key mechanisms in arterial stiffening with age and will be reviewed in the context of region-specific expression. In addition, interventions for attenuating age-related arterial stiffness and novel imaging advances for translating basic findings to older clinical populations will be discussed.

  • sodium nitrite de stiffening of large Elastic arteries with aging role of normalization of advanced glycation end products
    Experimental Gerontology, 2012
    Co-Authors: Bradley S Fleenor, Amy L Sindler, Devatha P Nair, Blair R Dodson, Douglas R Seals
    Abstract:

    Abstract We tested the hypothesis that sodium nitrite treatment reverses large Elastic Artery stiffening in old mice via reductions in collagen I, increases in elastin and/or decreases in advanced glycation end products (AGEs) mediated by reduced oxidative stress. Aortic pulse wave velocity (aPWV), a measure of large Elastic Artery stiffness, was greater in old (26–28 months) compared with young (4–6 months) control animals (520 ± 9 vs. 405 ± 6 cm/s, p

  • superoxide lowering therapy with tempol reverses arterial dysfunction with aging in mice
    Aging Cell, 2012
    Co-Authors: Bradley S Fleenor, Melanie L Zigler, Douglas R Seals, Amy L Sindler
    Abstract:

    To test the hypothesis that the antioxidant enzyme superoxide dismutase (SOD) mimetic TEMPOL improves arterial aging, young (Y, 4–6 mo) and old (O, 26–28 mo) male C57BL6 mice received regular or TEMPOL-supplemented (1mM) drinking water for 3 weeks (n=8/group). Aortic superoxide was 65% greater in O (p<0.05 vs. Y), which was normalized by TEMPOL. O had large Elastic Artery stiffening, as indicated by greater aortic pulse wave velocity (aPWV, 508 ± 22 vs. 418 ± 22 AU), which was associated with increased adventitial collagen I expression (p<0.05 vs. Y). TEMPOL reversed the age-associated increases in aPWV (434 ± 21 AU) and collagen in vivo, and SOD reversed increases in collagen I in adventitial fibroblasts from older rats in vitro. Isolated carotid arteries of O had impaired endothelial function as indicated by reduced acetylcholine-stimulated endothelium-dependent dilation (EDD) (75.6 ± 3.2 vs. 94.5 ± 2.0%) mediated by reduced nitric oxide (NO) bioavailability (L-NAME) associated with decreased endothelial NO synthase (eNOS) expression (p<0.05 vs. Y). TEMPOL restored EDD (94.5 ± 1.4%), NO bioavailability and eNOS in O. Nitrotyrosine and expression of NADPH oxidase were ~100–200% greater, and MnSOD was ~75% lower in O (p<0.05 vs. Y). TEMPOL normalized nitrotyrosine and NADPH oxidase in O, without affecting MnSOD. Aortic pro-inflammatory cytokines were greater in O (p<0.05 vs. Y) and normalized by TEMPOL. Short-term treatment of excessive superoxide with TEMPOL ameliorates large Elastic Artery stiffening and endothelial dysfunction with aging, and this is associated with normalization of arterial collagen I, eNOS, oxidative stress and inflammation.

Hirofumi Tanaka - One of the best experts on this subject based on the ideXlab platform.

  • association between central Elastic Artery stiffness and cerebral perfusion in deep subcortical gray and white matter
    American Journal of Hypertension, 2011
    Co-Authors: Takashi Tarumi, Hirofumi Tanaka, Furqan Shah, Andreana P Haley
    Abstract:

    BACKGROUND Central Elastic Artery stiffness can increase vascular resistance and induce hypertrophic remodeling of cerebral arterioles and, in turn, may increase the risk of cerebral hypoperfusion. In this study, we examined whether central Artery stiffness was directly associated with cerebral perfusion. METHODS Thirty-five adults (15 men and 20 women; 49 ± 7 years) were studied. Central Artery stiffness was determined by carotid-femoral pulse wave velocity (cfPWV). Regional cerebral perfusion in deep subcortical white and gray matter was measured using arterial spin labeling (ASL). RESULTS Participants were divided into two groups created by a median split of pooled subjects (median cfPWV = 1,090 cm/s). The group with high cfPWV showed significantly lower cerebral perfusion in frontal (29.9 ± 3.6 vs. 50.7 ± 3.7 ml/100 g/min, P = 0.001) and parietal (33.4 ± 6.0 vs. 57.5 ± 5.7 ml/100 g/min, P < 0.01) white matter and hippocampus (44.4 ± 4.4 vs. 60.1 ± 6.1 ml/100 g/min, P = 0.04) than the low cfPWV group. Simple correlation analysis revealed that cfPWV is significantly associated with cerebral perfusion in frontal (r = -0.64, P < 0.001) and parietal (r = -0.36, P = 0.03) white matter. Multiple linear regression analysis further indicated that 11% of the variability in frontal white matter perfusion (ΔR(2) = 0.11, P = 0.03) is explained by cfPWV (β = -0.54, P = 0.03), independent of age, sex, race, heart rate, blood pressure, and cardiovascular medication. CONCLUSIONS Central Elastic Artery stiffness is inversely and significantly associated with cerebral perfusion in deep subcortical frontal white matter, independent of potential confounding factors.

  • association between central Elastic Artery stiffness and cerebral perfusion in deep subcortical gray and white matter
    American Journal of Hypertension, 2011
    Co-Authors: Takashi Tarumi, Hirofumi Tanaka, Furqan Shah, Andreana P Haley
    Abstract:

    BackgR ound central Elastic Artery stiffness can increase vascular resistance and induce hypertrophic remodeling of cerebral arterioles and, in turn, may increase the risk of cerebral hypoperfusion. In this study, we examined whether central Artery stiffness was directly associated with cerebral perfusion. methodS thirty-five adults (15 men and 20 women; 49 ± 7 years) were studied. central Artery stiffness was determined by carotid-femoral pulse wave velocity (cfPWV). regional cerebral perfusion in deep subcortical white and gray matter was measured using arterial spin labeling (ASL). ReSult S Participants were divided into two groups created by a median split of pooled subjects (median cfPWV = 1,090 cm/s). the group with high cfPWV showed significantly lower cerebral perfusion in frontal (29.9 ± 3.6 vs. 50.7 ± 3.7 ml/100 g/min, P = 0.001) and parietal (33.4 ± 6.0 vs. 57.5 ± 5.7 ml/100 g/min, P < 0.01) white matter and hippocampus (44.4 ± 4.4 vs. 60.1 ± 6.1 ml/100 g/min, P = 0.04) than the low cfPWV group. Simple correlation analysis revealed that cfPWV is significantly associated with cerebral perfusion in frontal (r = −0.64, P < 0.001) and parietal (r = −0.36, P = 0.03) white matter. Multiple linear regression analysis further indicated that 11% of the variability in frontal white matter perfusion (∆R 2 = 0.11, P = 0.03) is explained by cfPWV (β = −0.54, P = 0.03), independent of age, sex, race, heart rate, blood pressure, and cardiovascular medication.

  • dietary sodium restriction rapidly improves large Elastic Artery compliance in older adults with systolic hypertension
    Hypertension, 2004
    Co-Authors: Phillip E Gates, Douglas R Seals, Hirofumi Tanaka, William R Hiatt
    Abstract:

    We determined the temporal effects of dietary sodium restriction on large Elastic Artery compliance and systolic blood pressure (SBP) in 12 untreated, older (64+/-2 years) men and women (6 each) with stage 1 systolic hypertension. After baseline measurements subjects were assigned to 4 weeks of low or normal sodium intake (randomized, crossover design). Urinary sodium excretion was reduced by 60% by the end of week 1 of sodium restriction (54+/-11 mmol/d, P 5 mm Hg by week 1 of sodium restriction, attaining peak reductions by week 2 (-12 mm Hg, P<0.01 versus baseline). The 24-hour ambulatory SBP was approximately 3 mm Hg lower at week 1 of sodium restriction and approximately 6 mm Hg lower by week 2 (P<0.01 versus baseline). The reductions in resting SBP from baseline to week 2 of sodium restriction were strongly related to the corresponding increases in carotid compliance (r=0.80, P<0.01). Urinary sodium excretion, carotid Artery compliance, and SBP were not different during normal sodium intake versus baseline. Other subject characteristics were not different across conditions. Sodium restriction rapidly improves large Elastic Artery compliance in older adults with stage 1 systolic hypertension. These improvements in central arterial compliance appear to be a key mechanism in the rapid normalization of SBP by sodium restriction in these patients.

  • dietary sodium restriction rapidly improves large Elastic Artery compliance in older adults with systolic hypertension
    Hypertension, 2004
    Co-Authors: Phillip E Gates, Douglas R Seals, Hirofumi Tanaka, William R Hiatt
    Abstract:

    We determined the temporal effects of dietary sodium restriction on large Elastic Artery compliance and systolic blood pressure (SBP) in 12 untreated, older (64±2 years) men and women (6 each) with stage 1 systolic hypertension. After baseline measurements subjects were assigned to 4 weeks of low or normal sodium intake (randomized, crossover design). Urinary sodium excretion was reduced by 60% by the end of week 1 of sodium restriction (54±11 mmol/d, P P P 5 mm Hg by week 1 of sodium restriction, attaining peak reductions by week 2 (−12 mm Hg, P P r =0.80, P

Phillip E Gates - One of the best experts on this subject based on the ideXlab platform.

  • decline in large Elastic Artery compliance with age a therapeutic target for habitual exercise
    British Journal of Sports Medicine, 2006
    Co-Authors: Phillip E Gates, Douglas R Seals
    Abstract:

    Aerobic exercise can favourably modify arterial compliance in middle-aged and older adults Cardiovascular diseases are prevalent in industrialised societies, and age is the dominant risk factor for morbidity and mortality.1 Consequently, a primary public health concern is to understand the mechanisms by which ageing is associated with cardiovascular diseases and to establish appropriate prevention and intervention strategies. One putative mechanism that has emerged as an important risk factor for cardiovascular disease is the age-associated decline in large Artery compliance.2,3 This single degenerative alteration to the vasculature has profound effects on cardiovascular health, contributing to increased systolic blood pressure and pulse pressure, isolated systolic hypertension, reduced cardiovagal baroreflex sensitivity, increased aortic input impedance, left ventricular hypertrophy and diastolic dysfunction, atherosclerosis, and congestive heart failure.1–4 As such, the age-associated decline in arterial compliance is an important therapeutic target for habitual physical activity in the prevention of cardiovascular diseases. The purpose of this article is to highlight recent studies from our laboratory and other peer-reviewed literature that provide compelling experimental evidence that aerobic exercise can favourably modify arterial compliance in middle-aged and older adults.5–8 We will also present evidence suggesting that resistance training is potentially detrimental to arterial compliance unless combined with aerobic exercise. Arterial compliance (and its inverse, arterial stiffness) describes the ability of an Artery to distend in response to a change in intravascular (transmural) pressure. By distending and recoiling, the large “Elastic” arteries in the cardiothoracic region—for example, aorta and carotid arteries—function to buffer the oscillation in blood pressure caused by ventricular pumping, and help to convert intermittent blood flow from the ventricle into continuous blood flow in the vasculature.9 This compliant property of the Artery is typically determined by simultaneous measurements of changes in arterial blood pressure and volume during the …

  • dietary sodium restriction rapidly improves large Elastic Artery compliance in older adults with systolic hypertension
    Hypertension, 2004
    Co-Authors: Phillip E Gates, Douglas R Seals, Hirofumi Tanaka, William R Hiatt
    Abstract:

    We determined the temporal effects of dietary sodium restriction on large Elastic Artery compliance and systolic blood pressure (SBP) in 12 untreated, older (64+/-2 years) men and women (6 each) with stage 1 systolic hypertension. After baseline measurements subjects were assigned to 4 weeks of low or normal sodium intake (randomized, crossover design). Urinary sodium excretion was reduced by 60% by the end of week 1 of sodium restriction (54+/-11 mmol/d, P 5 mm Hg by week 1 of sodium restriction, attaining peak reductions by week 2 (-12 mm Hg, P<0.01 versus baseline). The 24-hour ambulatory SBP was approximately 3 mm Hg lower at week 1 of sodium restriction and approximately 6 mm Hg lower by week 2 (P<0.01 versus baseline). The reductions in resting SBP from baseline to week 2 of sodium restriction were strongly related to the corresponding increases in carotid compliance (r=0.80, P<0.01). Urinary sodium excretion, carotid Artery compliance, and SBP were not different during normal sodium intake versus baseline. Other subject characteristics were not different across conditions. Sodium restriction rapidly improves large Elastic Artery compliance in older adults with stage 1 systolic hypertension. These improvements in central arterial compliance appear to be a key mechanism in the rapid normalization of SBP by sodium restriction in these patients.

  • dietary sodium restriction rapidly improves large Elastic Artery compliance in older adults with systolic hypertension
    Hypertension, 2004
    Co-Authors: Phillip E Gates, Douglas R Seals, Hirofumi Tanaka, William R Hiatt
    Abstract:

    We determined the temporal effects of dietary sodium restriction on large Elastic Artery compliance and systolic blood pressure (SBP) in 12 untreated, older (64±2 years) men and women (6 each) with stage 1 systolic hypertension. After baseline measurements subjects were assigned to 4 weeks of low or normal sodium intake (randomized, crossover design). Urinary sodium excretion was reduced by 60% by the end of week 1 of sodium restriction (54±11 mmol/d, P P P 5 mm Hg by week 1 of sodium restriction, attaining peak reductions by week 2 (−12 mm Hg, P P r =0.80, P