Published online before print May 2, 2005, doi: 10.1161/01.HYP.0000165678.63373.8c
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2005;45:1107.)
© 2005 American Heart Association, Inc.
Original Articles |
Ascorbic Acid Selectively Improves Large Elastic Artery Compliance in Postmenopausal Women
From the Department of Integrative Physiology (K.L.M., K.M.G., A.E.P., D.R.S.), University of Colorado at Boulder; and Division of Geriatric Medicine (K.L.M., D.R.S.), Department of Medicine, University of Colorado Health Sciences Center, Denver.
Correspondence to Kerrie L. Moreau, PhD, Department of Integrative Physiology, 354 UCB, University of Colorado at Boulder, Boulder, CO 80309-0354. E-mail moreauk{at}colorado.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
The compliance of large elastic arteries in the cardiothoracic region decreases with advancing age/menopause and plays an important role in the increased prevalence of cardiovascular diseases in postmenopausal women. We determined whether oxidative stress contributes to the reduced large elastic artery compliance of postmenopausal women. Carotid artery compliance was measured during acute intravenous infusions of saline (baseline control) and supraphysiological doses of the potent antioxidant ascorbic acid in premenopausal (n=10; 23±1; mean±SE) and estrogen-deficient postmenopausal (n=21; 55±1 years) healthy sedentary women. Carotid artery compliance was 56% lower in postmenopausal compared with premenopausal women during baseline control (P<0.0001). Ascorbic acid infusion increased carotid artery compliance by 26% in postmenopausal women (1.11±0.07 to 1.38±0.08 mm2/mm Hgx10–1; P<0.001) but had no effect in premenopausal women (2.50±0.25 versus 2.43±0.20 mm2/mm Hgx10–1). Carotid artery diameter, blood pressure, and heart rate were unaffected by ascorbic acid. In the pooled population, the change in arterial compliance with ascorbic acid correlated with baseline waist-to-hip ratio (r=0.56; P=0.001), plasma norepinephrine (r=0.58; P=0.001), and LDL cholesterol (r=0.54; P=0.001). These results suggest that oxidative stress may be an important mechanism contributing to the reduced large elastic artery compliance of sedentary, estrogen-deficient postmenopausal women. Increased abdominal fat storage, sympathetic nervous system activity, and LDL cholesterol may be mechanistically involved in oxidative stress–associated suppression of arterial compliance in postmenopausal women.
Key Words: aging • cholesterol • oxidative stress
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
Cardiovascular disease (CVD) is the leading cause of death in women in the United States.1 "Vascular aging" has been emphasized recently as the major risk factor for development of CVD.2 One clinically important change that occurs with vascular aging is a reduction in the compliance of large elastic arteries within the cardiothoracic region. In turn, this contributes to a number of adverse age-associated changes, including increased aortic impedance, left ventricular hypertrophy, and reduced cardiovagal baroreflex sensitivity.2–4 As such, identifying the mechanisms that contribute to reduced large elastic artery compliance with age is an important goal.2
Cardiovascular aging in women is unique in that it appears to be delayed or occurs at a slower rate than in men during the premenopausal years, thereafter "catching up" with men during the postmenopausal period, particularly in estrogen-deficient women.5–7 The mechanisms underlying the accelerated cardiovascular aging of estrogen-deficient postmenopausal women are unclear but could be related in part to the development of oxidative stress. Markers of oxidative stress are higher and endogenous antioxidant defenses lower in some estrogen-deficient postmenopausal women compared with premenopausal controls.8,9
Because oxidative stress modulates vascular smooth muscle cell (VSMC) tone, a key determinant of large artery compliance,10,11 we hypothesized that oxidative stress may contribute to the reduced large artery compliance of estrogen-deficient postmenopausal women. Moreover, because abdominal adiposity and LDL cholesterol levels are elevated in postmenopausal women12,13 and associated with oxidative stress,14,15 we determined whether these factors were related to oxidative stress–linked suppression of large artery compliance.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
Subjects
Thirty-one healthy women were studied: postmenopausal women (50 to 63 years of age) who were estrogen deficient (n=21) and 10 premenopausal controls (20 to 27 years of age). All subjects were sedentary (no aerobic exercise >2 days per week), normotensive, had a body mass index (BMI) <33 kg/m2, were nonsmokers, nonmedicated, and were free of overt chronic diseases as assessed by medical history, physical examination, standard blood chemistries, and hematologic evaluation. Women >50 years of age were further evaluated by ECG and blood pressure responses during incremental treadmill exercise to exhaustion. All postmenopausal women were
1 year without menses (menopause duration 8±2 years) and had not taken hormone replacement therapy for 6 months. Four postmenopausal women were initially taking either vitamin E or C and stopped 4 weeks before the main experimental protocol (methods on dietary analysis are located in the data supplement). All subjects gave their written informed consent to participate. All procedures were reviewed and approved by the University of Colorado at Boulder human research committee, and all subjects gave informed consent. All procedures were performed in the General Clinical Research Center (GCRC) and in accordance with University institutional guidelines.
Measurements
All measurements were performed after a 4-hour fast (12 hours for determination of metabolic parameters) and abstinence from caffeine. Premenopausal women were tested 1 to 6 days after onset of menstruation (ie, early follicular phase). During the main experimental sessions, the women were instrumented with an intravenous catheter in the arm for infusion of saline and ascorbic acid and acquisition of blood.
Large Elastic Artery Compliance
Carotid artery compliance and beta stiffness index, a less blood pressure–dependent expression of arterial compliance, were determined using high-resolution ultrasound imaging (Toshiba Power Vision 6000) along with applanation tonometric-obtained arterial pressure waveforms (SPT-301; Millar Instruments) from the contralateral artery as described previously.16,17 All images were coded by number and were blinded to group assignment.
Brachial Artery Blood Pressure
Peripheral arterial blood pressure was measured with a semiautomated device (Dinamap; Johnson & Johnson) over the brachial artery as described previously.16
Metabolic Risk Factors and Oxidative Stress Markers
Fasting plasma concentrations of cholesterol, glucose, and insulin, and endothelin-1 (competitive radioimmunoassay),18 and catecholamines19 were measured by the Core Laboratory of the University of Colorado GCRC as described previously.20 Total antioxidant status (TAS), a measure of the overall antioxidant defense system, was determined on serum samples as described by Miller et al21 (methods are detailed in the online data supplement, available at http://www.hypertensionaha.org). Oxidized LDL, an indirect measure of oxidative stress, was measured with an ELISA plate assay (Alpco Diagnostics).22
Body Composition
Total fat mass and fat-free mass and abdominal-to-thigh fat distribution were determined using dual-energy x-ray absorptiometry (DXA; DPX-IQ; Lunar Corp) as described in detail previously.23 Minimal waist and hip circumferences were measured according to previously published guidelines, and waist-to-hip ratio (WHR) was calculated.24
Protocol
To examine the contribution of oxidative stress to group differences in large elastic artery compliance, measurements were obtained during intravenous infusions of saline (baseline control) and a pharmacological dose of ascorbic acid (vitamin C) (American Regent Laboratories Inc) as described recently by our laboratory,25,26 and in detail in the online data supplement.
Statistical Analysis
Unpaired t tests were used to assess group differences in subject characteristics and oxidative stress markers. To determine the effect of acute ascorbic acid infusion on large elastic artery compliance, repeated-measures ANOVA was used. In case of a significant F value, a post hoc test with the Newman–Keuls method was used to identify significant differences among the mean values. Univariate and partial correlation analyses were used to determine the relationships between variables of interest.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
Subject Characteristics
The characteristics of the subject groups are presented in Table 1. There were no significant group differences in body mass, BMI, arterial blood pressure, endothelin-1, HDL cholesterol, plasma epinephrine, or fasting insulin concentrations. Body fat, waist circumference, WHR, abdominal-to-peripheral body fat distribution, total and LDL cholesterol, fasting glucose, plasma norepinephrine, and oxidized LDL were higher and TAS was lower in the postmenopausal compared with the premenopausal women (all P<0.05). There was a trend for total caloric (1787±100 versus 2158±163 kcal per day) and carbohydrate (51±2% versus 58±3%) intake to be lower in the postmenopausal women (both P=0.06). There were no differences between the premenopausal and postmenopausal women in any other macronutrients, vitamins, or alcohol intake (data not shown).
|
Large Elastic Artery Compliance
Baseline carotid artery compliance was 56% lower (P<0.001) in the postmenopausal versus premenopausal women (Figure 1). Similar results were obtained when the data were expressed as beta stiffness index (Figure 1).
|
P<0.001 vs saline of the same group.
Ascorbic acid infusion increased large elastic artery compliance by 26±4% in the postmenopausal women (1.11±0.07 to 1.38±0.08 mm2/mm Hgx10–1; P<0.001) but had no effect in premenopausal (2.50±0.25 versus 2.43±0.25 mm2/mm Hgx10–1; 
–5±6%; Figures 1 and 2
). Similar results were observed when the data were expressed as beta stiffness index. Arterial blood pressure (brachial and carotid), heart rate, and carotid artery diameter remained unchanged with ascorbic acid infusion (all P>0.50; Table 2).
|
|
Correlates of Large Elastic Artery Compliance at Baseline and With Ascorbic Acid
In the pooled subjects, baseline carotid artery compliance was inversely related to oxidized LDL (r=–0.46), fasting glucose (r=–0.43), WHR (r=–0.63), abdominal-to-thigh body fat distribution (r=–0.41), plasma norepinephrine (r=–0.50), LDL cholesterol (r=–0.51) and total cholesterol (r=–0.52; all P<0.02) and positively related to TAS (r=0.45; P=0.02).
In the pooled subjects, the changes in carotid artery compliance from baseline in response to ascorbic acid administration were most strongly related to plasma norepinephrine (r=0.58; P=0.001; Figure 3), WHR (r=0.56; P=0.001; Figure 3), and LDL cholesterol (r=0.54; P=0.001; Figure 3), total cholesterol (r=0.45; P=0.007), fasting glucose (r=0.48; P=0.005), and abdominal-to-thigh body fat distribution (r=0.32; P=0.05). When the effects of age were partialed out, only LDL cholesterol correlated with the change in arterial compliance in response to ascorbic acid. Within the postmenopausal women, LDL cholesterol (r=0.40; P<0.05), were related to the change in arterial compliance with ascorbic acid [plasma norepinephrine (r=0.40), and WHR (r=0.34; both P=0.06)]. There were no significant correlations within the premenopausal women. Use of beta stiffness index instead of arterial compliance resulted in the same general relations.
|
) and postmenopausal (•) women. |
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
The novel finding of the present study is that oxidative stress appears to contribute mechanistically to the reduced large elastic artery compliance of estrogen-deficient postmenopausal women. Moreover, our results suggest that the modulatory influence of oxidative stress on large artery compliance is most closely related to baseline abdominal fat storage, sympathetic nervous system activity (plasma norepinephrine concentrations), and circulating LDL cholesterol.
Oxidative Stress and Carotid Artery Compliance in Premenopausal and Postmenopausal Women
Estrogen-deficient postmenopausal women appear to develop oxidative stress as a result of increased production of reactive oxygen species or reduced endogenous antioxidants.8,9 The higher oxidized LDL and lower TAS plasma concentrations in the postmenopausal compared with the premenopausal women in the present study are consistent with this idea.
The new key finding of the present study is that acute administration of the potent antioxidant ascorbic acid (vitamin C) increased carotid artery compliance in estrogen-deficient postmenopausal women but not in premenopausal controls. These results suggest that oxidative stress tonically suppresses large elastic artery compliance in healthy estrogen-deficient postmenopausal women. Administration of antioxidants, including vitamins C and E, have been reported previously to modulate systemic arterial compliance, large artery stiffness, or pulse wave augmentation in adult humans, including patients with type 2 diabetes and CVD.27–30 The present findings extend these observations by demonstrating a tonic inhibitory effect of oxidative stress on carotid artery compliance in healthy estrogen-deficient postmenopausal women that is not observed in premenopausal females.
Consistent with the present results in premenopausal females, our laboratory demonstrated recently that acute and chronic ascorbic acid administration have no effect on carotid artery compliance in healthy young males.25 However, in apparent contrast to the present findings, no improvement in carotid artery compliance was observed in older men in response to ascorbic acid.25 It is unclear why arterial compliance increased with the ascorbic acid infusion in our postmenopausal women but not in the older men studied previously by our laboratory. Intrinsic differences may exist between women and men with aging that differentially affect arterial sensitivity to antioxidants. For example, estrogen or its metabolites have physiologically significant antioxidant properties that increase NO bioavailability and, thus, relax VSMCs.31–33 This, in turn, presumably would act to increase arterial compliance. Perhaps the loss of circulating estrogen with menopause results in an antioxidant deficit, leading to an increase in VSMC responsiveness to ascorbic acid administration.
Mechanisms of Oxidative Stress–Associated Modulation of Carotid Artery Compliance
We can only speculate on the mechanisms by which oxidative stress may contribute to impaired large artery compliance in postmenopausal estrogen-deficient women. Menopause is associated with metabolic changes, including increased visceral adiposity and plasma cholesterol,12,13 and obesity and dyslipidemia are associated with oxidative stress, independent of age and menopause.14,15 In addition, abdominal obesity is associated with elevated sympathetic nervous system activity and norepinephrine release,34 which, in itself, can contribute to in vivo oxidative stress.35 In the present study, whole-body and abdominal fat (estimated using waist circumference, WHR, and abdominal-to-peripheral body fat distribution), plasma norepinephrine, and LDL cholesterol were higher in the postmenopausal compared with the premenopausal women. Moreover, measures of abdominal adiposity (r=0.46 to 50; P<0.005), norepinephrine (r=0.35; P<0.05), and LDL cholesterol (r=0.35; P<0.05) correlated with oxidized LDL and were the strongest correlates of the change in arterial compliance from baseline in response to ascorbic acid infusion. Thus, increased abdominal adiposity, sympathetic nervous system activity/norepinephrine release, and circulating cholesterol may contribute to the development of oxidative stress and its inhibition of large elastic artery compliance in postmenopausal females.
The exact mechanism by which ascorbic acid selectively improved large artery compliance in our postmenopausal women is unclear. Ascorbic acid is a potent water-soluble antioxidant that destroys reactive oxygen species. Structural changes within the elastin–collagen composition of the arterial wall are thought to occur over a period of years, making it unlikely that an acute intravenous infusion of ascorbic acid could improve large elastic artery compliance via such mechanisms.36,37 Rather, the ability of short-term administration of ascorbic acid to augment arterial compliance is more likely mediated by suppressing the effects of oxidative stress on vascular smooth muscle tone, perhaps in part through actions on the vascular endothelium.26,38 Specifically, ascorbic acid may increase NO bioavailability by protecting NO from inactivation by reactive oxygen species, which would increase the tonic state of VSMC relaxation.39 Increased NO bioavailability in the setting of reduced oxidative stress also may decrease tonic 
-adrenergic receptor–mediated contraction of VSMCs by suppressing norepinephrine release from sympathetic nerve endings or by uncoupling norepinephrine and -adrenergic signal transduction.40,41
Considerations and Experimental Limitations
The fact that carotid artery compliance was not restored to premenopausal levels with ascorbic acid infusion in either group of postmenopausal women indicates that other mechanisms besides oxidative stress are contributing to the reduced large elastic artery compliance in the postmenopausal state. These other mechanisms may include extracellular matrix–linked structural alterations within the arterial wall, including the formation of advanced glycation end-products.42 Additionally, it is possible that there was residual oxidative stress that was not influenced by ascorbic acid, and thus, other antioxidants (eg, vitamin E and glutathione) may have produced further improvements in or restored arterial compliance. Clearly, the most effective approach to acutely reducing oxidative stress would be to inhibit all sources of production of reactive oxygen species; however, this is not possible at the present time.
There are several limitations associated with the present study. First, we used indirect systemic plasma biomarkers of oxidative stress and antioxidant capacity, which lack sensitivity and may not accurately reflect the amount of oxidative stress in the vasculature. However, despite this, we were able to show the expected group differences in oxidized LDL and TAS, as well as significant relationships between these markers and baseline measures of large artery compliance. Second, we did not measure ascorbic acid concentrations or oxidative stress markers during the infusions. However, we have shown previously that the same infusion dose of ascorbic acid increases plasma ascorbic acid to supraphysiological levels (
15-fold higher than baseline levels)25,26,43–45 and decreases plasma oxidized LDL and isoprostane concentrations.43,44 Moreover, in the present study, we were able to demonstrate a significant increase in large elastic artery compliance with ascorbic acid in the postmenopausal women, the group postulated to have baseline oxidative stress.
It is important to emphasize that the aim of the present study was to test the hypothesis that oxidative stress contributes mechanistically to reduced large elastic artery compliance in postmenopausal women, not to determine the efficacy of oral vitamin C supplementation as a potential intervention. Recent clinical trial data demonstrate no effect of vitamin C or E on CVD outcomes.46,47 This lack of effect is likely explained in part by the fact that oral vitamin C supplementation cannot maintain plasma ascorbic acid concentrations at levels required to scavenge reactive oxygen species.26,48 Indeed, improvements in intermediary cardiovascular risk factors in response to acute administration of supraphysiological levels of ascorbic acid are not necessarily observed with longer-term oral supplementation.26
Perspectives
Our findings may have important clinical implications. CVD is now acknowledged to be a major public health concern for women.49 In this regard, vascular aging featuring, in part, a decrease in large elastic artery compliance has been emphasized recently as the major risk factor involved in the etiology of CVD.2 As such, a better understanding of the mechanisms mediating reductions in large elastic artery compliance with aging in women is needed. The results of the present study provide new insight into the potential pathophysiological role of oxidative stress in the reduced large elastic artery compliance observed in postmenopausal women, a group at increased risk of CVD.
|
Conclusions |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
In conclusion, the results of the present study support the idea that oxidative stress plays an important mechanistic role in the reduction in large elastic artery compliance in estrogen-deficient postmenopausal sedentary women. Increased abdominal fat storage, sympathetic nervous system activity, and circulating cholesterol may be factors involved in the oxidative stress–associated reduction in large elastic artery compliance in this group.
|
Acknowledgments |
|---|
This study was supported by National Institutes of Health awards AG06537, AG20683, AG22241, and AG13038, and by the General Clinical Research Center (RR-00051).
Received January 20, 2005; first decision February 3, 2005; accepted March 30, 2005.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionConclusionsReferences |
|---|
- American Heart Association. Heart Disease and Stroke Statistics—2005 Update. Dallas, Tex: American Heart Association; 2004.
- Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a "set up" for vascular disease. Circulation. 2003; 107: 139–146.
[Free Full Text] - Bonhay I, Jokkel G, Kollai M. Relation between baroreflex sensitivity and carotid artery elasticity in healthy humans. Am J Physiol. 1996; 271: H1139–H1144.[Medline] [Order article via Infotrieve]
- Bouthier JD, De Luca N, Safar ME, Simon AC. Cardiac hypertrophy and arterial distensibility in essential hypertension. Am Heart J. 1985; 109: 1345–1352.[CrossRef][Medline] [Order article via Infotrieve]
- McGrath BP, Liang YL, Teede H, Shiel LM, Cameron JD, Dart A. Age-related deterioration in arterial structure and function in postmenopausal women: impact of hormone replacement therapy. Arterioscler Thromb Vasc Biol. 1998; 18: 1149–1156.
[Abstract/Free Full Text] - Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H. Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women. Cardiovasc Res. 2003; 57: 861–868.
[Abstract/Free Full Text] - Nagai Y, Earley CJ, Kemper MK, Bacal CS, Metter EJ. Influence of age and postmenopausal estrogen replacement therapy on carotid arterial stiffness in women. Cardiovasc Res. 1999; 41: 307–311.
[Abstract/Free Full Text] - Ozden S, Dildar K, Kadir YH, Gulizar K. The effects of hormone replacement therapy on lipid peroxidation and antioxidant status. Maturitas. 2001; 38: 165–170.[CrossRef][Medline] [Order article via Infotrieve]
- Leal M, Diaz J, Serrano E, Abellan J, Carbonell LF. Hormone replacement therapy for oxidative stress in postmenopausal women with hot flushes. Obstet Gynecol. 2000; 95: 804–809.
[Abstract/Free Full Text] - Wilkinson IB, Franklin SS, Cockcroft JR. Nitric oxide and the regulation of large artery stiffness: from physiology to pharmacology. Hypertension. 2004; 44: 112–116.
[Free Full Text] - Wilkinson IB, Qasem A, McEniery CM, Webb DJ, Avolio AP, Cockcroft JR. Nitric oxide regulates local arterial distensibility in vivo. Circulation. 2002; 105: 213–217.
[Abstract/Free Full Text] - Toth MJ, Tchernof A, Sites CK, Poehlman ET. Menopause-related changes in body fat distribution. Ann N Y Acad Sci. 2000; 904: 502–506.
[Abstract/Free Full Text] - Gower BA, Nagy TR, Goran MI, Toth MJ, Poehlman ET. Fat distribution and plasma lipid-lipoprotein concentrations in pre- and postmenopausal women. Int J Obes Relat Metab Disord. 1998; 22: 605–611.[CrossRef][Medline] [Order article via Infotrieve]
- Vassalle C, Petrozzi L, Botto N, Andreassi MG, Zucchelli GC. Oxidative stress and its association with coronary artery disease and different atherogenic risk factors. J Intern Med. 2004; 256: 308–315.[CrossRef][Medline] [Order article via Infotrieve]
- Keaney JF Jr, Larson MG, Vasan RS, Wilson PW, Lipinska I, Corey D, Massaro JM, Sutherland P, Vita JA, Benjamin EJ. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol. 2003; 23: 434–439.
[Abstract/Free Full Text] - Tanaka H, Dinenno FA, Monahan KD, Clevenger CM, DeSouza CA, Seals DR. Aging, habitual exercise, and dynamic arterial compliance. Circulation. 2000; 102: 1270–1275.
[Abstract/Free Full Text] - Armentano R, Megnien JL, Simon A, Bellenfant F, Barra J, Levenson J. Effects of hypertension on viscoelasticity of carotid and femoral arteries in humans. Hypertension. 1995; 26: 48–54.
[Abstract/Free Full Text] - Lerman A, Edwards BS, Hallett JW, Heublein DM, Sandberg SM, Burnett JC Jr. Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. N Engl J Med. 1991; 325: 997–1001.[Abstract]
- Peuler JD, Johnson GA. Simultaneous single isotope radioenzyme assay of plasma norepinephrine, epinephrine, and dopamine. Life Sci. 1977; 21: 625–636.[CrossRef][Medline] [Order article via Infotrieve]
- Stevenson ET, Davy KP, Seals DR. Hemostatic, metabolic, and androgenic risk factors for coronary heart disease in physically active and less active postmenopausal women. Arterioscler Thromb Vasc Biol. 1995; 15: 669–677.
[Abstract/Free Full Text] - Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V, Milner A. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci (Lond). 1993; 84: 407–412.[Medline] [Order article via Infotrieve]
- Holvoet P, Vanhaecke J, Janssens S, Van de Werf F, Collen D. Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease. Circulation. 1998; 98: 1487–1494.
[Abstract/Free Full Text] - Christou DD, Jones PP, Pimentel AE, Seals DR. Increased abdominal-to-peripheral fat distribution contributes to altered autonomic-circulatory control with human aging. Am J Physiol Heart Circ Physiol. 2004; 287: H1530–H1537.
[Abstract/Free Full Text] - Lohman TG, Roche AF, Martorell R. Anthropometric Standardization Reference Manual. Champaign, Ill: Human Kinetics; 1988.
- Eskurza I, Monahan KD, Robinson JA, Seals DR. Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men. Am J Physiol Heart Circ Physiol. 2004; 286: H1528–H1534.
[Abstract/Free Full Text] - Eskurza I, Monahan KD, Robinson JA, Seals DR. Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol. 2004; 556: 315–324.
[Abstract/Free Full Text] - Mottram P, Shige H, Nestel P. Vitamin E improves arterial compliance in middle-aged men and women. Atherosclerosis. 1999; 145: 399–404.[CrossRef][Medline] [Order article via Infotrieve]
- Mullan BA, Ennis CN, Fee HJ, Young IS, McCance DR. Protective effects of ascorbic acid on arterial hemodynamics during acute hyperglycemia. Am J Physiol Heart Circ Physiol. 2004; 287: H1262–H1268.
[Abstract/Free Full Text] - Mullan BA, Young IS, Fee H, McCance DR. Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes. Hypertension. 2002; 40: 804–809.
[Abstract/Free Full Text] - Wilkinson IB, Megson IL, MacCallum H, Sogo N, Cockcroft JR, Webb DJ. Oral vitamin C reduces arterial stiffness and platelet aggregation in humans. J Cardiovasc Pharmacol. 1999; 34: 690–693.[CrossRef][Medline] [Order article via Infotrieve]
- Hernandez I, Delgado JL, Diaz J, Quesada T, Teruel MJ, Llanos MC, Carbonell LF. 17beta-estradiol prevents oxidative stress and decreases blood pressure in ovariectomized rats. Am J Physiol Regul Integr Comp Physiol. 2000; 279: R1599–R1605.
[Abstract/Free Full Text] - Keaney JF Jr, Shwaery GT, Xu A, Nicolosi RJ, Loscalzo J, Foxall TL, Vita JA. 17 beta-estradiol preserves endothelial vasodilator function and limits low-density lipoprotein oxidation in hypercholesterolemic swine. Circulation. 1994; 89: 2251–2259.
[Abstract/Free Full Text] - Virdis A, Ghiadoni L, Pinto S, Lombardo M, Petraglia F, Gennazzani A, Buralli S, Taddei S, Salvetti A. Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women. Circulation. 2000; 101: 2258–2263.
[Abstract/Free Full Text] - Jones PP, Davy KP, Alexander S, Seals DR. Age-related increase in muscle sympathetic nerve activity is associated with abdominal adiposity. Am J Physiol. 1997; 272: E976–E980.[Medline] [Order article via Infotrieve]
- Aizawa T, Ishizaka N, Usui S-I, Ohashi N, Ohno M, Nagai R. Angiotensin II and catecholamines increase plasma levels of 8-epi-prostaglandin F2{alpha} with different pressor dependencies in rats. Hypertension. 2002; 39: 149–154.
[Abstract/Free Full Text] - O’Rourke M. Arterial stiffness, systolic blood pressure, and logical treatment of arterial hypertension. Hypertension. 1990; 15: 339–347.
[Abstract/Free Full Text] - O’Rourke MF, Avolio AP, Lauren PD, Young J. Age-related changes of elastic lamellae in the human thoracic aorta. J Am Coll Cardiol. 1987; 9: 53A.
- Taddei S, Virdis A, Ghiadoni L, Salvetti G, Bernini G, Magagna A, Salvetti A. Age-related reduction of NO availability and oxidative stress in humans. Hypertension. 2001; 38: 274–279.
[Abstract/Free Full Text] - May JM. How does ascorbic acid prevent endothelial dysfunction? Free Radic Biol Med. 2000; 28: 1421–1429.[CrossRef][Medline] [Order article via Infotrieve]
- Zanzinger J. Role of nitric oxide in the neural control of cardiovascular function. Cardiovasc Res. 1999; 43: 639–649.
[Abstract/Free Full Text] - Zanzinger J, Czachurski J, Seller H. Inhibition of sympathetic vasoconstriction is a major principle of vasodilation by nitric oxide in vivo. Circ Res. 1994; 75: 1073–1077.
[Abstract/Free Full Text] - Kass DA, Shapiro EP, Kawaguchi M, Capriotti AR, Scuteri A, deGroof RC, Lakatta EG. Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation. 2001; 104: 1464–1470.
[Abstract/Free Full Text] - Bell C, Carson JM, Motte NW, Seals DR. Ascorbic acid does not affect the age-associated reduction in maximal cardiac output and oxygen consumption in healthy adults. J Appl Physiol. 2005; 98: 845–849.
[Abstract/Free Full Text] - Bell C, Jones PP, Seals DR. Oxidative stress does not modulate metabolic rate or skeletal muscle sympathetic activity with primary aging in adult humans. J Clin Endocrinol Metab. 2003; 88: 4950–4954.
[Abstract/Free Full Text] - Monahan KD, Eskurza I, Seals DR. Ascorbic acid increases cardiovagal baroreflex sensitivity in healthy older men. Am J Physiol Heart Circ Physiol. 2004; 286: H2113–H2117.
[Abstract/Free Full Text] - Hodis HN, Mack WJ, LaBree L, Mahrer PR, Sevanian A, Liu CR, Liu CH, Hwang J, Selzer RH, Azen SP. Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the Vitamin E Atherosclerosis Prevention Study (VEAPS). Circulation. 2002; 106: 1453–1459.
[Abstract/Free Full Text] - Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, Ouyang P, Thompson P, Tardif JC, Higginson L, Bittner V, Steffes M, Gordon DJ, Proschan M, Younes N, Verter JI. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. J Am Med Assoc. 2002; 288: 2432–2440.
[Abstract/Free Full Text] - Jackson TS, Xu A, Vita JA, Keaney JF Jr. Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations. Circ Res. 1998; 83: 916–922.
[Abstract/Free Full Text] - Mosca L, Appel LJ, Benjamin EJ, Berra K, Chandra-Strobos N, Fabunmi RP, Grady D, Haan CK, Hayes SN, Judelson DR, Keenan NL, McBride P, Oparil S, Ouyang P, Oz MC, Mendelsohn ME, Pasternak RC, Pinn VW, Robertson RM, Schenck-Gustafsson K, Sila CA, Smith SC Jr, Sopko G, Taylor AL, Walsh BW, Wenger NK, Williams CL. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation. 2004; 109: 672–693.
[Free Full Text]
This article has been cited by other articles:
 |
|
 |
|
  K. L. Jablonski, D. R. Seals, I. Eskurza, K. D. Monahan, and A. J. Donato High-dose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men J Appl Physiol, November 1, 2007; 103(5): 1715 - 1721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Donato, I. Eskurza, A. E. Silver, A. S. Levy, G. L. Pierce, P. E. Gates, and D. R. Seals Direct Evidence of Endothelial Oxidative Stress With Aging in Humans: Relation to Impaired Endothelium-Dependent Dilation and Upregulation of Nuclear Factor-{kappa}B Circ. Res., June 8, 2007; 100(11): 1659 - 1666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Moreau, A. R. DePaulis, K. M. Gavin, and D. R. Seals Oxidative stress contributes to chronic leg vasoconstriction in estrogen-deficient postmenopausal women J Appl Physiol, March 1, 2007; 102(3): 890 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Kregel and H. J. Zhang An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R18 - R36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. O. Palmieri, I. Grattagliano, P. Portincasa, and G. Palasciano Systemic Oxidative Alterations Are Associated with Visceral Adiposity and Liver Steatosis in Patients with Metabolic Syndrome J. Nutr., December 1, 2006; 136(12): 3022 - 3026. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||