A differing role of oxidative stress in the regulation of central and peripheral hemodynamics during exercise in heart failure

This study sought to characterize the role of free radicals in regulating central and peripheral hemodynamics at rest and during exercise in patients with heart failure (HF). We examined cardiovascular responses to dynamic handgrip exercise (4, 8, and 12 kg at 1 Hz) following consumption of either a placebo or acute oral antioxidant cocktail (AOC) consisting of vitamin C, E, and α-lipoic acid in a balanced, crossover design. Central and peripheral hemodynamics, mean arterial pressure, cardiac index, systemic vascular resistance (SVR), brachial artery blood flow, and peripheral (arm) vascular resistance (PVR) were determined in 10 HF patients and 10 age-matched controls. Blood assays evaluated markers of oxidative stress and efficacy of the AOC. When compared with controls, patients with HF exhibited greater oxidative stress, measured by malondialdehyde (+36%), and evidence of endogenous antioxidant compensation, measured by greater superoxide dismutase activity (+83%). The AOC increased plasma ascorbate (+50%) in both the HF patients and controls, but significant systemic hemodynamic effects were only evident in the patients with HF, both at rest and throughout exercise. Specifically, the AOC reduced mean arterial pressure (−5%) and SVR (−12%) and increased cardiac index (+7%) at each workload. In contrast, peripherally, brachial artery blood flow and PVR (arm) were unchanged by the AOC. In conclusion, these data imply that SVR in patients with HF is, at least in part, mediated by oxidative stress. However, this finding does not appear to be the direct result of muscle-specific changes in PVR.

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Oxidative stress contributes to chronic leg vasoconstriction in estrogen-deficient postmenopausal women

Journal of Applied Physiology ◽

10.1152/japplphysiol.00877.2006 ◽

2007 ◽

Vol 102 (3) ◽

pp. 890-895 ◽

Cited By ~ 18

Author(s):

Kerrie L. Moreau ◽

Ashley R. DePaulis ◽

Kathleen M. Gavin ◽

Douglas R. Seals

Keyword(s):

Oxidative Stress ◽

Blood Flow ◽

Ascorbic Acid ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Postmenopausal Women ◽

Oxidized Ldl ◽

Duplex Ultrasound ◽

Vascular Conductance ◽

Leg Blood Flow

Basal whole leg blood flow and vascular conductance are reduced in estrogen-deficient postmenopausal compared with premenopausal women. The underlying mechanisms are unknown, but oxidative stress could be involved. We studied 9 premenopausal [23 ± 1 yr (mean ± SE)] and 20 estrogen-deficient postmenopausal (55 ± 1 yr) healthy women. During baseline control, oxidized low-density lipoprotein (LDL), a marker of oxidative stress, was 50% greater in the postmenopausal women ( P < 0.001). Basal whole leg blood flow (duplex ultrasound of femoral artery) was 34% lower in the postmenopausal women because of a 38% lower leg vascular conductance ( P < 0.0001); mean arterial pressure was not different. Intravenous administration of a supraphysiological dose of the antioxidant ascorbic acid increased leg blood flow by 15% in the postmenopausal women as a result of an increase in leg vascular conductance (both P < 0.001), but it did not affect leg blood flow in premenopausal controls or mean arterial pressure in either group. In the pooled subjects, the changes in leg blood flow and leg vascular conductance with ascorbic acid were related to baseline plasma oxidized LDL ( r = 0.46 and 0.53, P < 0.01) and waist-to-hip ratio and total body fat ( r = 0.41–0.44, all P < 0.05). Our results are consistent with the hypothesis that oxidative stress contributes to chronic leg vasoconstriction and reduced basal whole leg blood flow in estrogen-deficient postmenopausal women. This oxidative stress-related suppression of leg vascular conductance and blood flow may be linked in part to increased total and abdominal adiposity.

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NOS inhibition blunts and delays the compensatory dilation in hypoperfused contracting human muscles

Journal of Applied Physiology ◽

10.1152/japplphysiol.00680.2009 ◽

2009 ◽

Vol 107 (6) ◽

pp. 1685-1692 ◽

Cited By ~ 26

Author(s):

Darren P. Casey ◽

Michael J. Joyner

Keyword(s):

Blood Flow ◽

Steady State ◽

Arterial Pressure ◽

Brachial Artery ◽

Muscle Blood Flow ◽

Systemic Arterial Pressure ◽

Balloon Inflation ◽

Forearm Vascular Conductance ◽

Forearm Exercise

We previously demonstrated that skeletal muscle blood flow is restored in the exercising forearm during experimental hypoperfusion via local dilator and/or myogenic mechanisms. This study examined the role of nitric oxide (NO) in the restoration of blood flow to the active muscles during hypoperfusion. Eleven healthy subjects (10 men/1 woman; 25 ± 1 yr of age) performed rhythmic forearm exercise (10% and 20% of maximum) while hypoperfusion was evoked by balloon inflation in the brachial artery above the elbow. Each trial included baseline, exercise, exercise with inflation, and exercise after deflation (3 min each). Forearm blood flow (FBF; ultrasound) and local (brachial artery catheter pressure, BAP) and systemic arterial pressure [mean arterial pressure (MAP); Finometer] were measured. The exercise bouts were repeated during NG-monomethyl-l-arginine (l-NMMA) infusion (NO synthase inhibition). Forearm vascular conductance (FVC; ml·min−1·100 mmHg−1) was calculated from BF (ml/min) and BAP (mmHg). FBF and FVC fell acutely with balloon inflation during all trials ( P < 0.01). Recovery of FBF and FVC [(inflation − nadir)/(steady-state exercise − nadir)] with l-NMMA administration was reduced during 20% exercise (FBF = 77 ± 7% vs. 88 ± 8%; FVC = 71 ± 8% vs. 90 ± 9%; P < 0.01) but not 10% exercise (FBF = 83 ± 4% vs. 81 ± 5%, P = 0.37; FVC = 75 ± 10% vs. 76 ± 7%; P = 0.44) compared with the respective control trial. The time to steady-state vasodilator response was substantially longer during the l-NMMA trials (10% = 74 ± 4 s vs. 61 ± 6 s; 20% = 53 ± 4 s vs. 41 ± 4 s; P < 0.05). Thus the magnitude and timing of the NO contribution to compensatory dilation during forearm exercise with hypoperfusion was dependent on exercise intensity. These observations suggest that NO is released by contracting muscles or that a portion of the dilation caused by ischemic metabolites is NO dependent.

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Exercise-induced brachial artery blood flow and vascular function is impaired in systemic sclerosis

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00547.2016 ◽

2016 ◽

Vol 311 (6) ◽

pp. H1375-H1381 ◽

Cited By ~ 1

Author(s):

Daniel R. Machin ◽

Heather L. Clifton ◽

Ryan S. Garten ◽

Jayson R. Gifford ◽

Russell S. Richardson ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Flow ◽

Systemic Sclerosis ◽

Brachial Artery ◽

Vascular Function ◽

Vascular Dysfunction ◽

Artery Blood Flow ◽

Handgrip Exercise ◽

Brachial Artery Diameter ◽

Exercise Induced

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by debilitating fibrosis and vascular dysfunction; however, little is known about the circulatory response to exercise in this population. Therefore, we examined the peripheral hemodynamic and vasodilatory responses to handgrip exercise in 10 patients with SSc (61 ± 4 yr) and 15 age-matched healthy controls (56 ± 5 yr). Brachial artery diameter, blood flow, and mean arterial pressure (MAP) were determined at rest and during progressive static-intermittent handgrip exercise. Patients with SSc and controls were similar in body stature, handgrip strength, and MAP; however, brachial artery blood flow at rest was nearly twofold lower in patients with SSc compared with controls (22 ± 4 vs. 42 ± 5 ml/min, respectively; P < 0.05). Additionally, SSc patients had an ∼18% smaller brachial artery lumen diameter with an ∼28% thicker arterial wall at rest ( P < 0.05). Although, during handgrip exercise, there were no differences in MAP between the groups, exercise-induced hyperemia and therefore vascular conductance were ∼35% lower at all exercise workloads in patients with SSc ( P < 0.05). Brachial artery vasodilation, as assessed by the relationship between Δbrachial artery diameter and Δshear rate, was significantly attenuated in the patients with SSc ( P < 0.05). Finally, vascular dysfunction in the patients with SSc was accompanied by elevated blood markers of oxidative stress and attenuated endogenous antioxidant activity ( P < 0.05). Together, these findings reveal attenuated exercise-induced brachial artery blood flow and conduit arterial vasodilatory dysfunction during handgrip exercise in SSc and suggest that elevated oxidative stress may play a role.

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Heart failure patients demonstrate impaired changes in brachial artery blood flow and shear rate pattern during moderate-intensity cycle exercise

Experimental Physiology ◽

10.1113/ep085040 ◽

2015 ◽

Vol 100 (4) ◽

pp. 463-474 ◽

Cited By ~ 6

Author(s):

Nathalie M. M. Benda ◽

Joost P. H. Seeger ◽

Dirk P. T. van Lier ◽

Louise Bellersen ◽

Arie P. J. van Dijk ◽

...

Keyword(s):

Heart Failure ◽

Blood Flow ◽

Shear Rate ◽

Brachial Artery ◽

Moderate Intensity ◽

Artery Blood Flow ◽

Cycle Exercise ◽

Heart Failure Patients

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Central and peripheral contributors to skeletal muscle hyperemia: response to passive limb movement

Journal of Applied Physiology ◽

10.1152/japplphysiol.00895.2009 ◽

2010 ◽

Vol 108 (1) ◽

pp. 76-84 ◽

Cited By ~ 33

Author(s):

John McDaniel ◽

Anette S. Fjeldstad ◽

Steve Ives ◽

Melissa Hayman ◽

Phil Kithas ◽

...

Keyword(s):

Heart Rate ◽

Blood Flow ◽

Cardiac Output ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Stroke Volume ◽

Limb Movement ◽

Leg Blood Flow ◽

Passive Exercise

The central and peripheral contributions to exercise-induced hyperemia are not well understood. Thus, utilizing a reductionist approach, we determined the sequential peripheral and central responses to passive exercise in nine healthy men (33 ± 9 yr). Cardiac output, heart rate, stroke volume, mean arterial pressure, and femoral blood flow of the passively moved leg and stationary (control) leg were evaluated second by second during 3 min of passive knee extension with and without a thigh cuff that occluded leg blood flow. Without the thigh cuff, significant transient increases in cardiac output (1.0 ± 0.6 l/min, Δ15%), heart rate (7 ± 4 beats/min, Δ12%), stroke volume (7 ± 5 ml, Δ7%), passive leg blood flow (411 ± 146 ml/min, Δ151%), and control leg blood flow (125 ± 68 ml/min, Δ43%) and a transient decrease in mean arterial pressure (3 ± 3 mmHg, 4%) occurred shortly after the onset of limb movement. Although the rise and fall rates of these variables differed, they all returned to baseline values within 45 s; therefore, continued limb movement beyond 45 s does not maintain an increase in cardiac output or net blood flow. Similar changes in the central variables occurred when blood flow to the passively moving leg was occluded. These data confirm the role of peripheral factors and reveal an essential supportive role of cardiac output in the hyperemia at the onset of passive limb movement. This cardiac output response provides an important potential link between the physiology of active and passive exercise.

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The Effect of Maternal Hypoxemia on the Umbilical and Femoral Artery Blood Flow Velocity Waveforms and the Relationship with Mean Arterial Pressure in Fetal Sheep

Gynecologic and Obstetric Investigation ◽

10.1159/000292653 ◽

1993 ◽

Vol 35 (1) ◽

pp. 1-6

Author(s):

Guido J.J.M. Muijsers ◽

Hans van Huisseling ◽

Tom H.M. Hasaart

Keyword(s):

Blood Flow ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Flow Velocity ◽

Femoral Artery ◽

Blood Flow Velocity ◽

Artery Blood Flow ◽

Fetal Sheep ◽

Femoral Artery Blood Flow ◽

The Relationship

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Altered muscle metaboreflex control of coronary blood flow and ventricular function in heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00985.2004 ◽

2005 ◽

Vol 288 (3) ◽

pp. H1381-H1388 ◽

Cited By ~ 29

Author(s):

Eric J. Ansorge ◽

Robert A. Augustyniak ◽

Mariana L. Perinot ◽

Robert L. Hammond ◽

Jong-Kyung Kim ◽

...

Keyword(s):

Heart Failure ◽

Heart Rate ◽

Blood Flow ◽

Cardiac Output ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Coronary Blood Flow ◽

Moderate Exercise ◽

Muscle Metaboreflex ◽

Significant Change

We investigated the effect of muscle metaboreflex activation on left circumflex coronary blood flow (CBF), coronary vascular conductance (CVC), and regional left ventricular performance in conscious, chronically instrumented dogs during treadmill exercise before and after the induction of heart failure (HF). In control experiments, muscle metaboreflex activation during mild exercise elicited significant reflex increases in mean arterial pressure, heart rate, and cardiac output. CBF increased significantly, whereas no significant change in CVC occurred. There was no significant change in the minimal rate of myocardial shortening (−d l/d tmin) with muscle metaboreflex activation during mild exercise (15.5 ± 1.3 to 16.8 ± 2.4 mm/s, P > 0.05); however, the maximal rate of myocardial relaxation (+d l/d tmax) increased (from 26.3 ± 4.0 to 33.7 ± 5.7 mm/s, P < 0.05). Similar hemodynamic responses were observed with metaboreflex activation during moderate exercise, except there were significant changes in both −d l/d tmin and d l/d tmax. In contrast, during mild exercise with metaboreflex activation during HF, no significant increase in cardiac output occurred, despite a significant increase in heart rate, inasmuch as a significant decrease in stroke volume occurred as well. The increases in mean arterial pressure and CBF were attenuated, and a significant reduction in CVC was observed (0.74 ± 0.14 vs. 0.62 ± 0.12 ml·min−1·mmHg−1; P < 0.05). Similar results were observed during moderate exercise in HF. Muscle metaboreflex activation did not elicit significant changes in either −d l/d tmin or +d l/d tmax during mild exercise in HF. We conclude that during HF the elevated muscle metaboreflex-induced increases in sympathetic tone to the heart functionally vasoconstrict the coronary vasculature, which may limit increases in myocardial performance.

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