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Donato A J, Uberoi A, Bailey DM, Wray DW, Richardson RS. Exercise-induced brachial artery vasodilation: effects of antioxidants and exercise training in elderly men. Am J Physiol Heart Circ Physiol 298: H671-H678, 2010. First published December 4, 2009; doi: 10.1152/ajpheart.00761.2009.--Aging, vascular function, and exercise are thought to have a common link in oxidative stress. Of the 28 subjects studied (young, 26 [+ or -] 2 yr; old, 71 [+ or -] 6 yr), 12 took part in a study to validate an antioxidant cocktail (AOC: vitamins C, E, and [alpha]-lipoic acid), while the remaining 8 young and 8 old subjects performed submaximal forearm handgrip exercise with placebo or AOC. Old subjects repeated forearm exercise with placebo or AOC following knee-extensor (KE) exercise training. Brachial arterial diameter and blood velocity (Doppler ultrasound) were measured at rest and during exercise. During handgrip exercise, brachial artery vasodilation in the old subjects was attenuated compared with that in young subjects following placebo (maximum = ~3.0 and ~6.0%, respectively). In contrast to the previously documented attenuation in exercise-induced brachial artery vasodilation in the young group with AOC, in the old subjects the AOC restored vasodilation (maximum = ~7.0%) to match the young. KE training also improved exerciseinduced brachial artery vasodilation. However, in the trained state, AOC administration no longer augmented brachial artery vasodilation in the elderly, but rather attenuated it. These data reveal an age-related pro-/antioxidant imbalance that impacts vascular function and show that exercise training is capable of restoring equilibrium such that vascular function is improved and the AOC-mediated reduction in free radicals now negatively impacts brachial artery vasodilation, as seen in the young. aging; free radicals; oxidative stress; arterial function doi: 10.1152/ajpheart.00761.2009

Flow-mediated dilatation (%FMD), an index of nitric oxide (NO)-mediated vasodilator function, is regarded as a surrogate marker of cardiovascular disease. Aging is associated with endothelial dysfunction, but underlying sex-related differences may exist and the effects of fitness and exercise on endothelial dysfunction in men (M) and women (W) are poorly understood. We compared %FMD of the brachial artery in 18 young [Y, 26 [+ or -] 1 yr; 9 M and 9 W], 12 older fit (OF, 57 [+ or -] 2 yr; 6 M and 6 W), and 16 older sedentary (OS, 59 [+ or -] 2 yr; 8 M and 8 W) subjects. Glyceryl trinitrate (GTN) administration was used to assess endothelium-independent vasodilatation, and the FMD-to-GTN ratio was calculated to characterize NO dilator function in the context of smooth muscle cell sensitivity. Brachial %FMD in Y (7.1 [+ or -] 0.8%) was significantly higher compared with OS (4.8 [+ or -] 0.7%, P < 0.05), but not OF (6.4 [+ or -] 0.7%). Differences between Y and OS subjects were due primarily to lower FMD in the OS women (4.3 [+ or -] 0.6%). OS women exhibited significantly lower FMD-to-GTN ratios compared with Y (P < 0.05) and OF women (P < 0.05), whereas these differences were not apparent in men. Exercise training improved brachial artery NO dilator function (FMD-to-GTN ratio) after 24 wk (P < 0.05) in OS women, but not men. These findings indicate that maintaining a high level of fitness, or undertaking exercise training, prevents the age-related decline in the brachial artery vasodilator function evident in women. In OS men, who had relatively preserved NO dilator function, no training adaptations were observed. This study has potential implications for the prevention of conduit artery endothelial dysfunction in men and women. fitness; exercise training; upper-limb nitric oxide dilator function

We investigated the quantitative contribution of all local conduit arterial, blood, and distal load properties to the pressure transfer function from brachial artery to aorta. The model was based on anatomical data, Young's modulus, wall viscosity, blood viscosity, and blood density. A three-element wind-kessel represented the distal arterial tree. Sensitivity analysis was performed in terms of frequency and magnitude of the peak of the transfer function and in terms of systolic, diastolic, and pulse pressure in the aorta. The root mean square error (RMSE) described the accuracy in wave-shape prediction. The percent change of these variables for a 25% alteration of each of the model parameters was calculated. Vessel length and diameter are found to be the most important parameters determining pressure transfer. Systolic and diastolic pressure changed blood pressure; transfer function; personalization; brachial artery; aorta

The myogenic response, the inherent ability of blood vessels to rapidly respond to changes in transmural pressure, is involved in local blood flow autoregulation. Animal studies suggest that aging impairs the myogenic response. The purpose of this study was to compare the effects of changes in transmural pressure on mean blood velocity (MBV, cm/s) in young and older subjects. Twelve younger men and women (25 [+ or -] 1 yr) were gender and body composition matched to twelve older men and women (65 [+ or -] 1 yr). A specially designed tank raised or lowered forearm pressure by 50 mmHg within 0.2 s. Brachial artery MBV was measured directly above the site of forearm pressure change using Doppler methods. In response to increasing transmural pressure (i.e., release of +50 mmHg), older subjects compared with younger subjects had significantly lower peak MBV ([DELTA] 12.43 [+ or -] 1.16 vs. [DELTA] 17.97 [+ or -] 2.01 cm/s; P < 0.05), reduced rates in the dynamic fall of MBV after peak values were achieved (vasoconstriction) (-1.88 [+ or -] 0.17 vs. -2.90 [+ or -] 0.28 cm x [s.sup.-1] x [s.sup.-1]; P < 0.05), and lower MBV values with sustained suction. In response to decreasing transmural pressure (i.e., change to +50 mmHg), there was a significantly greater increase in MBV (A peak flow from trough 7.71 [+ or -] 1.32 vs. 4.38 [+ or -] 0.71 cm/s; P < 0.05) and a trend toward a greater rate of rise in MBV (vasodilation; 1.61 [+ or -] 0.29 vs. 0.96 [+ or -] 0.21 cm x [s.sup.-1] x [s.sup.-1]; P = 0.08) in the older subjects. Older subjects compared with the younger subjects exhibited decreased dynamic vasoconstriction, enhanced steady-state constriction, as well as evidence for enhanced dynamic vasodilation responses to sustained alterations in forearm transmural pressure. regional blood flow; blood pressure; circulation

Previous studies suggest that the blood pressure response to static contraction is greater than that caused by dynamic exercise. In anesthetized cats, however, pressor responses to electrically induced static and dynamic contraction of the same muscle group are similar during equivalent workloads and peak tension development [i.e., similar tension-time index (TTI)]. To determine if the same relationship exists in humans, where contraction is voluntary and central command is present, dynamic (180 s; 1/s) and static (90 s) contractions at 30% of maximal voluntary contraction (MVC) were performed. Dynamic contraction also was repeated at the same TTI for 90 s at 60% MVC. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), MAP during postexercise arterial occlusion (an index of the metaboreceptor-induced activation of the exercise pressor reflex), and relative perceived exertion (RPE) (an index of central command) were assessed. No differences in these variables were found between static and dynamic contraction at a tension of 30% MVC. During dynamic contraction at 60% MVC, changes in MAP (16 [+ or -] 3 vs. 19 [+ or -] 4 mmHg) and absolute HR (92 [+ or -] 6 vs. 69 [+ or -] 5 beats/min), CO (7.9 [+ or -] 0.4 vs. 6.3 [+ or -] 0.3 l/min), RPE (16 [+ or -] 1 vs. 13 [+ or -] 1), and MAP during postexercise arterial occlusion (115 [+ or -] 3 vs. 100 [+ or -] 4 mmHg) were greater than during static contraction (P < 0.05). Thus increases in MAP and HR, activation of central command, and muscle metabolite-induced stimulation of the exercise pressor reflex during static and dynamic contraction in humans seem to be similar when peak tension and TTI are equal. Augmented responses to dynamic contraction at 60% MVC are likely related to greater activation of these two mechanisms. exercise pressor reflex; central command; brachial artery blood flow; tension-time index

The roles of acetylcholine and nitric oxide (NO) in regulating the time course and magnitude of change in the forearm blood flow (FBF) were determined through experiments in humans during and after voluntary rhythmic exercise. Results have shown that both cholinergic and noncholinergic NO-related mechanisms regulated basal forearm blood circulation. It was indicated that neither acetylcholine nor NO mediated the magnitude or rate of increase in exercise FBF.

A study was conducted on the effects of vitamin C and cigarette smoking on endothelium-dependent vasodilation. Measurements were made of lumen diameter and flow velocity of the brachial arteries at rest, during reactive hyperemia and after sublingual nitroglycerin. The results indicate that endothelium-dependent vasodilation in the brachial arteries is impaired in smokers, which can be improved by vitamin C administration.

A mathematical model of the arm tissue mechanical behavior under the effect of external pressure loads is presented. The model has been used to study stress and strain distribution across the tissue, and pressure transmission to the brachial artery, when the arm is compressed by two adjacent cuffs independently inflated. Using this configuration, the tissue elastic parameters (Young modulus and Poisson ratio) can be individually identified using a simple and noninvasive experimental procedure. Model validation has been achieved by comparing its results with data obtained experimentally on 10 subjects. These comparisons demonstrate that the proposed model may constitute a simple but valid new tool able to describe tissue behavior, subjected to external pressures, with sufficient accuracy. Joined with a model of brachial hemodynamics, it might contribute to improve our understanding of noninvasive blood pressure estimation techniques.

The main biomechanical factors which may affect the accuracy of the oscillometric method for indirect blood pressure measurement are analyzed using a new model of brachial hemodynamics. In a first stage of this work, the model has been used to reproduce some well-known responses of collapsing arteries, such as the sharp increase in compliance, and the nonlinear pressure-flow characteristic with negative dynamic resistance. In a second stage the model has been linked to the arm tissue mechanics description presented in a previous work. The final model so obtained has then been employed to analyze the pattern of the main hemodynamic quantities (pressure pulsations in the cuffs, blood volume changes, blood flow upstream and downstream of the cuffs) during deflation manoeuvres. The simulation results agree with those found in the recent literature quite well. Results indicate that the cuff pressure value for maximum pulsations exhibits a large plateau, located approximately around the mean arterial pressure. However, stiffness of wall artery, or stretching of the cuff internal surface, may significantly alter the obtained results causing a phenomena of 'pseudo-hypertension.'

Ringqvist, Asa, Kenneth Caidahl, Ann-Sofi Petersson, and Ake Wennmalm. Diurnal variation of flow-mediated vasodilation in healthy premenopausal women. Am J Physiol Heart Circ Physiol 279: H2720-H2725, 2000.--The present study was designed to test the hypothesis of a diurnal variation of endothelial function. Sixteen healthy, nonsmoking women were studied, each on four occasions during one 24-h period (2:00 PM, 8:00 PM, 2:00 AM, and 8:00 AM). Endothelial function was assessed by ultrasound determinations of flow-mediated vasodilation (FMD%) in the brachial artery. FMD% was contrasted with endothelium-independent vasodilation, i.e., nitroglycerine-induced vasodilation (NTG%). Additionally, plasma concentrations and urinary excretion of nitrate and cGMP were analyzed. FMD% and NTG% displayed diurnal, albeit not parallel, patterns of variation. Whereas FMD% gradually increased from 2:00 PM and peaked at 2:00 AM (means [+ or -] SE: 3.1 [+ or -] 0.4, 4.4 [+ or -] 0.4, 5.1 [+ or -] 0.9, and 3.9 [+ or -] 0.8%), the NTG% demonstrated a nadir at 2:00 AM. Plasma levels and urinary excretion of nitrate and cGMP did not display diurnal variation and no clear association with the variations seen in FMD% and NTG%. This study demonstrates a diurnal variation in both endothelium-dependent and -independent vasodilation in the brachial artery of healthy women. The background and possible implication of such a variation require further studies. nitric oxide; nitrate; guanosine 3',5'-cyclic monophosphate; endothelium; catecholamines