Ascorbic Acid Selectively Improves Large Elastic Artery Compliance in Postmenopausal Women

Abstract

Abstract-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 (nϭ10; 23Ϯ1; meanϮSE) and estrogen-deficient postmenopausal (nϭ21; 55Ϯ1 years) healthy sedentary women. Carotid artery compliance was 56% lower in postmenopausal compared with premenopausal women during baseline control (PϽ0.0001 ). 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 (rϭ0.56; Pϭ0.001), plasma norepinephrine (rϭ0.58; Pϭ0.001), and LDL cholesterol (rϭ0.54; Pϭ0.001). 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 Ⅲ cholesterol Ⅲ oxidative stress C ardiovascular 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][3][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 estrogendeficient women. [5][6][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-defic...

Direct Evidence of Endothelial Oxidative Stress With Aging in Humans

“…[5][6][7]13,25 Our finding that plasma oxidized LDL concentrations, a systemic marker of oxidative stress, 26 were greater in older men is in agreement with previous observations from our laboratory in similarly healthy, well-screened men and postmenopausal women. 5,20 The present results extend these findings by providing direct evidence of oxidative stress in ECs from older adults. Specifically, we found that nitrotyrosine, which reflects nitration of tyrosine residues on proteins 27 and, thus, serves as an indicator of oxidative stress, 28 is elevated in ECs collected from the brachial artery and peripheral veins of older compared with young healthy men.…”

“…Plasma samples were analyzed for oxidized low-density lipoprotein, a marker of systemic oxidative stress, and serum samples were analyzed for total antioxidant status, a measure of systemic antioxidant defenses, as previously described. 20 Serum concentrations of C-reactive protein were measured using a high-sensitivity ELISA (Olympus AU400e Chemistry Analyzer and reagents). Dietary intake of macro-and micronutrients was estimated from 4-day diet records as described previously.…”

Increased proinflammatory and oxidant gene expression in circulating mononuclear cells in older adults: amelioration by habitual exercise

“…Several conventional and nonconventional risk factors for CVD change with age, even in healthy adults (9,10,14,23), as was the case in the present study (Table 1). However, these factors were not significant predictors of the age-associated MCP-1, B), and interleukin-6 (IL-6, C) in peripheral blood mononuclear cells from sedentary (Sed) young and older adults (n ϭ 8 -14/group).…”

“…Fasting circulating metabolic factors were determined by standard assays at the CTRC core laboratory. Plasma samples were analyzed for oxidized low-density lipoprotein (LDL), a marker of systemic oxidative stress, and serum samples were analyzed for total antioxidant status, as previously described (23). Serum concentrations of the inflammatory markers C-reactive protein (CRP), TNF-␣, and IL-6 were measured as previously described (9).…”

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

“…Nrf-2, the master transcription factor that regulates antioxidant genes, is protective in maternal diabetes-induced perinatal hypertension (30,221). Antioxidant vitamins reduced blood pressure and arterial stiffness in patients with diabetes (240), but had no effect in postmenopausal women or in healthy subjects (140). Population studies have demonstrated an inverse association between plasma vitamin C levels and vitamin C consumption with blood pressure (28,139), and a recent meta-analysis reported that vitamin C supplementation reduced systolic and diastolic blood pressure (147).…”