scholarly journals Systemic and regional hemodynamic response to activation of the exercise pressor reflex in patients with peripheral artery disease

2020 ◽  
Vol 318 (4) ◽  
pp. H916-H924 ◽  
Author(s):  
Danielle Jin-Kwang Kim ◽  
Marcos Kuroki ◽  
Jian Cui ◽  
Zhaohui Gao ◽  
J. Carter Luck ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Peripheral Artery Disease ◽  
Plantar Flexion ◽  
Peripheral Artery ◽  
Exercise Pressor Reflex ◽  
Femoral Blood Flow ◽  
Femoral Blood ◽  
Pressor Reflex ◽  
Artery Disease

Patients with peripheral artery disease (PAD) have an accentuated exercise pressor reflex (EPR) during exercise of the affected limb. The underlying hemodynamic changes responsible for this, and its effect on blood flow to the exercising extremity, are unclear. We tested the hypothesis that the exaggerated EPR in PAD is mediated by an increase in total peripheral resistance (TPR), which augments redistribution of blood flow to the exercising limb. Twelve patients with PAD and 12 age- and sex-matched subjects without PAD performed dynamic plantar flexion (PF) using the most symptomatic leg at progressive workloads of 2–12 kg (increased by 1 kg/min until onset of fatigue). We measured heart rate, beat-by-beat blood pressure, femoral blood flow velocity (FBV), and muscle oxygen saturation ([Formula: see text]) continuously during the exercise. Femoral blood flow (FBF) was calculated from FBV and baseline femoral artery diameter. Stroke volume (SV), cardiac output (CO), and TPR were derived from the blood pressure tracings. Mean arterial blood pressure and TPR were significantly augmented in PAD compared with control during PF. FBF increased during exercise to an equal extent in both groups. However, [Formula: see text] of the exercising limb remained significantly lower in PAD compared with control. We conclude that the exaggerated pressor response in PAD is mediated by an abnormal TPR response, which augments redistribution of blood flow to the exercising extremity, leading to an equal rise in FBF compared with controls. However, this increase in FBF is not sufficient to normalize the SmO2 response during exercise in patients with PAD. NEW & NOTEWORTHY In this study, peripheral artery disease (PAD) patients and healthy control subjects performed graded, dynamic plantar flexion exercise. Data from this study suggest that previously reported exaggerated exercise pressor reflex in patients with PAD is driven by greater vasoconstriction in nonexercising vascular territories which also results in a redistribution of blood flow to the exercising extremity. However, this rise in femoral blood flow does not fully correct the oxygen deficit due to changes in other mechanisms that require further investigation.

Abstract 15456: Enhanced Vasoconstrictor Sensitivity to Exercise Pressor Reflex Engagement in Peripheral Artery Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Zhaohui Gao ◽  
Matthew D Muller ◽  
Cheryl Blaha ◽  
Aimee Cauffman ◽  
Kristen Brandt ◽  
...  
Keyword(s):  
Blood Flow ◽  
Peripheral Artery Disease ◽  
Plantar Flexion ◽  
Maximum Voluntary Contraction ◽  
Ankle Brachial Index ◽  
Peak Exercise ◽  
Peripheral Artery ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Artery Disease

Exercise is associated with a rise in heart rate, blood pressure (BP) and blood flow to active skeletal muscle that is mediated by the exercise pressor reflex and modified by regional release of vasodilator factors. In peripheral artery disease (PAD) the exercise pressor reflex is enhanced and the ability to raise blood flow to the affected limb is impaired. To assess the functional impact of the enhanced exercise pressor reflex on regional blood flow in limbs affected by PAD, we determined beat-by-beat BP and mean blood velocity (MBV, Doppler) in the popliteal artery, and calculated vascular conductance index (VC, MBV/mean BP) in the exercising (ipsilateral) or contralateral resting leg during graded rhythmic plantar flexion exercise in 7 patients with symptomatic PAD (age 67±2 yrs, body-mass-index 27.9±1.1) and in 5 healthy age-matched controls (2 exercise trials with each leg). At peak exercise (2.0 kg, 1 contraction/sec), the pressor effect was greatest in PAD when exercise was performed with the “ischemic” leg (ankle-brachial index 0.58±0.05; mean ΔBP +9.1±2.0 mmHg), lower with the less affected leg (ankle brachial index 0.76±0.07; mean ΔBP +6.9±1.6 mmHg) and lowest in the controls (ankle brachial index 1.11±0.04; mean ΔBP +3.9±1.8 mmHg). In controls, VC increased in the exercising leg ( P <0.05) but did not change in the inactive contralateral leg ( P =NS). Similarly, in PAD, VC increased in the exercising “ischemic” leg ( P <0.05) but did not change in the inactive contralateral leg ( P =NS). In sharp contrast, while VC increased in the less affected exercising leg ( P <0.05), in the contralateral resting “ischemic” leg VC decreased by 24±10% ( P <0.05). Similarly, when static handgrip at 30% maximum voluntary contraction to fatigue served as the exercise stimulus, vasoconstriction was noted in the “ischemic” leg (n=5; P <0.05). Thus, unlike in the exercising leg, in the resting “ischemic” leg activation of the exercise pressor reflex resulted in substantial vasoconstriction. This suggests that despite activation of peripheral vasodilator mechanisms downstream to the arterial obstruction, the vasculature of the “ischemic” leg is exquisitely sensitive to reflex vasoconstriction.

scholarly journals Chronic femoral artery ligation exaggerates the pressor and sympathetic nerve responses during dynamic skeletal muscle stretch in decerebrate rats

2018 ◽  
Vol 314 (2) ◽  
pp. H246-H254 ◽  
Author(s):  
Evan A. Kempf ◽  
Korynne S. Rollins ◽  
Tyler D. Hopkins ◽  
Alec L. Butenas ◽  
Joseph M. Santin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Peripheral Artery Disease ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Peripheral Artery ◽  
Nerve Activity ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Artery Disease ◽  
Dynamic Stretch

Mechanical and metabolic signals arising during skeletal muscle contraction reflexly increase sympathetic nerve activity and blood pressure (i.e., the exercise pressor reflex). In a rat model of simulated peripheral artery disease in which a femoral artery is chronically (~72 h) ligated, the mechanically sensitive component of the exercise pressor reflex during 1-Hz dynamic contraction is exaggerated compared with that found in normal rats. Whether this is due to an enhanced acute sensitization of mechanoreceptors by metabolites produced during contraction or involves a chronic sensitization of mechanoreceptors is unknown. To investigate this issue, in decerebrate, unanesthetized rats, we tested the hypothesis that the increases in mean arterial blood pressure and renal sympathetic nerve activity during 1-Hz dynamic stretch are larger when evoked from a previously “ligated” hindlimb compared with those evoked from the contralateral “freely perfused” hindlimb. Dynamic stretch provided a mechanical stimulus in the absence of contraction-induced metabolite production that closely replicated the pattern of the mechanical stimulus present during dynamic contraction. We found that the increases in mean arterial blood pressure (freely perfused: 14 ± 1 and ligated: 23 ± 3 mmHg, P = 0.02) and renal sympathetic nerve activity were significantly greater during dynamic stretch of the ligated hindlimb compared with the increases during dynamic stretch of the freely perfused hindlimb. These findings suggest that the exaggerated mechanically sensitive component of the exercise pressor reflex found during dynamic muscle contraction in this rat model of simulated peripheral artery disease involves a chronic sensitizing effect of ligation on muscle mechanoreceptors and cannot be attributed solely to acute contraction-induced metabolite sensitization. NEW & NOTEWORTHY We found that the pressor and sympathetic nerve responses during dynamic stretch were exaggerated in rats with a ligated femoral artery (a model of peripheral artery disease). Our findings provide mechanistic insights into the exaggerated exercise pressor reflex in this model and may have important implications for peripheral artery disease patients.

scholarly journals Endoperoxide 4 receptors play a role in evoking the exercise pressor reflex in rats with simulated peripheral artery disease

2013 ◽  
Vol 591 (11) ◽  
pp. 2949-2962 ◽  
Author(s):  
Katsuya Yamauchi ◽  
Joyce S. Kim ◽  
Audrey J. Stone ◽  
Victor Ruiz-Velasco ◽  
Marc P. Kaufman
Keyword(s):  
Peripheral Artery Disease ◽  
Peripheral Artery ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Artery Disease

Sensory neuron inositol-1,4,5-trisphosphate (IP3) receptors contribute to chronic mechanoreflex sensitization in rats with simulated peripheral artery disease

2021 ◽  
Author(s):  
Korynne S. Rollins ◽  
Alec L E Butenas ◽  
Auni C Williams ◽  
Steven W. Copp
Keyword(s):  
Skeletal Muscle ◽  
Receptor Antagonist ◽  
Sensory Neuron ◽  
Peripheral Artery Disease ◽  
Femoral Artery ◽  
Pressor Response ◽  
Peripheral Artery ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Artery Disease

The mechanoreflex is exaggerated in patients with peripheral artery disease (PAD) and in a rat model of simulated PAD in which a femoral artery is chronically (~72hrs) ligated. We found recently that, in rats with a ligated femoral artery, blockade of thromboxane A2 (TxA2) receptors on the sensory endings of thin fiber muscle afferents reduced the pressor response to 1 Hz repetitive/dynamic hindlimb skeletal muscle stretch (a model of mechanoreflex activation isolated from contraction-induced metabolite production). Conversely, we found no effect of TxA2 receptor blockade in rats with freely perfused femoral arteries. Here we extended the isolated mechanoreflex findings in "ligated" rats to experiments evoking dynamic hindlimb skeletal muscle contractions. We also investigated the role played by inositol 1-4-5-trisphosphate (IP3) receptors, receptors associated with intracellular signaling linked to TxA2 receptors, in the exaggerated response to dynamic mechanoreflex and exercise pressor reflex activation in ligated rats. Injection of the TxA2 receptor antagonist daltroban into the arterial supply of the hindlimb reduced the pressor response to 1 Hz dynamic contraction in ligated but not "freely perfused" rats. Moreover, injection of the IP3 receptor antagonist xestospongin C into the arterial supply of the hindlimb reduced the pressor response to 1 Hz dynamic stretch and contraction in ligated but not freely perfused rats. These findings demonstrate that, in rats with a ligated femoral artery, sensory neuron TxA2 receptor and IP3 receptor mediated signaling contributes to a chronic sensitization of the mechanically activated channels associated with the mechanoreflex and the exercise pressor reflex.

scholarly journals The role played by oxidative stress in evoking the exercise pressor reflex in health and simulated peripheral artery disease

2017 ◽  
Vol 595 (13) ◽  
pp. 4365-4378 ◽  
Author(s):  
Jonathan E. Harms ◽  
J. Matthew Kuczmarski ◽  
Joyce S. Kim ◽  
Gail D. Thomas ◽  
Marc P. Kaufman
Keyword(s):  
Oxidative Stress ◽  
Peripheral Artery Disease ◽  
Peripheral Artery ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Artery Disease

scholarly journals Blockade of the TP receptor attenuates the exercise pressor reflex in decerebrated rats with chronic femoral artery occlusion

2011 ◽  
Vol 301 (5) ◽  
pp. H2140-H2146 ◽  
Author(s):  
Anna K. Leal ◽  
Jennifer L. McCord ◽  
Hirotsugu Tsuchimochi ◽  
Marc P. Kaufman
Keyword(s):  
Peripheral Artery Disease ◽  
Pressor Response ◽  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Peripheral Artery ◽  
Exercise Pressor Reflex ◽  
Tp Receptor ◽  
Static Contraction ◽  
Pressor Reflex ◽  
Artery Disease

Cyclooxygenase metabolites stimulate or sensitize group III and IV muscle afferents, which comprise the sensory arm of the exercise pressor reflex. The thromboxane (TP) receptor binds several of these metabolites, whose concentrations in the muscle interstitium are increased by exercise under freely perfused conditions and even more so under ischemic conditions, which occur in peripheral artery disease. We showed that the exercise pressor reflex is greater in rats with simulated peripheral artery disease than in rats with freely perfused limbs. These findings prompted us to test the hypothesis that the TP receptor contributes to the exaggerated exercise pressor reflex occurring in a rat model of peripheral artery disease. We compared the cardiovascular responses to static contraction and stretch before and after femoral arterial injections of daltroban (80 μg), a TP receptor antagonist. We performed these experiments in decerebrate rats whose femoral arteries were ligated 72 h before the experiment (a model of simulated peripheral artery disease) and in control rats whose hindlimbs were freely perfused. Daltroban reduced the pressor response to static contraction in both freely perfused ( n = 6; before: Δ12 ± 2 mmHg, after: Δ6 ± 2 mmHg, P = 0.024) and 72-h-ligated rats ( n = 10; before: Δ25 ± 3 mmHg, after: Δ7 ± 4 mmHg, P = 0.001). Likewise, daltroban reduced the pressor response to stretch in the freely perfused group ( n = 9; before: Δ30 ± 3 mmHg, after: Δ17 ± 3 mmHg, P < 0.0001) and in the ligated group ( n = 11; before: Δ37 ± 5 mmHg, after: Δ23 ± 3 mmHg, P = 0.016). Intravenous injections of daltroban had no effect on the pressor response to contraction. We conclude that the TP receptor contributes to the pressor responses evoked by contraction and stretch in both freely perfused rats and rats with simulated peripheral artery disease.

scholarly journals Peripheral µ-opioid receptors attenuate the responses of group III and IV afferents to contraction in rats with simulated peripheral artery disease

2018 ◽  
Vol 119 (6) ◽  
pp. 2052-2058 ◽  
Author(s):  
Jonathan Harms ◽  
Audrey J. Stone ◽  
Marc P. Kaufman
Keyword(s):  
Peripheral Artery Disease ◽  
Group Iv ◽  
Peripheral Artery ◽  
Opioid Agonist ◽  
Group Iii ◽  
Femoral Arteries ◽  
Exercise Pressor Reflex ◽  
Static Contraction ◽  
Pressor Reflex ◽  
Artery Disease

Patients with peripheral artery disease show an exaggerated pressor response to mild exercise, an effect attributable to the exercise pressor reflex, whose afferent arm comprises the thinly myelinated group III and unmyelinated group IV afferents. Previously, we found that DAMGO, a µ-opioid agonist injected into the femoral artery, attenuated the exaggerated exercise pressor reflex in rats with ligated femoral arteries, a preparation that simulates the blood flow patterns to muscle that is seen in patients with peripheral artery disease. Continuing this line of investigation, we recorded the responses of group III and IV afferents to static contraction before and after injecting DAMGO (1 µg) into the superficial epigastric artery in rats with patent femoral arteries and in rats with ligated femoral arteries. In rats with patent arteries, DAMGO did not change the responses to contraction of either group III ( n = 9; P = 0.83) or group IV ( n = 8; P = 0.34) afferents. In contrast, in rats with ligated femoral arteries, DAMGO injection (1 µg) significantly decreased the responses to contraction of both group III afferents ( n = 9, P < 0.01) and group IV afferents ( n = 9; P < 0.01). DAMGO did not significantly attenuate the responses of either group III or IV afferents to capsaicin in rats with either patent or ligated femoral arteries. These findings are in agreement with our previous studies that showed that peripheral DAMGO injection attenuated the exercise pressor reflex in rats with ligated femoral arteries but had only a modest effect on the exercise pressor reflex in rats with patent femoral arteries. NEW & NOTEWORTHY In an animal model of peripheral artery disease, we show that the µ-opioid agonist, DAMGO reduces the afferent response rate resulting from stimulated static contraction. These results suggest that peripherally active opioid agonists that do not cross the blood-brain barrier may be therapeutic for treatment of peripheral artery disease without the negative and addictive side effects associated with opioids in the central nervous system.

Abstract 11611: Muscle Superoxide Dismutase and Augmented Autonomic Responsiveness in Rats With Peripheral Artery Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jihong Xing ◽  
Jian Lu ◽  
Jiahao Liu ◽  
Jianhua Li
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Muscle Contraction ◽  
Peripheral Artery Disease ◽  
Optical Density ◽  
Blood Pressure Response ◽  
Pressure Response ◽  
Static Exercise ◽  
Peripheral Artery ◽  
Artery Disease

Background: During exercise, responses of sympathetic nerve and blood pressure are amplified in patients with peripheral artery disease (PAD). This worsens the restricted blood flow directed to the limbs in this disease. The purpose of this study was to determine the role played by muscle oxidative stress in regulating the augmented autonomic responses to static exercise in PAD. Superoxide dismutases (SOD) is a class of enzymes to catalyze the dismutation of superoxide into oxygen and hydrogen peroxide, and considered as an important antioxidant. Thus, our specific hypothesis was that limb ischemia impairs muscle SOD and thereby leads to abnormal autonomic responsiveness observed in PAD. Methods and Results: We used a rat model of femoral artery ligation to study PAD. Note that all data are presented as mean ± SE. First, western blot analysis shows that 72 hours of femoral occlusion significantly decreased the protein levels of SOD in the oxidative muscle (optical density: 1.02±0.03 in control vs. 0.21±0.02 after ligation, P< 0.05; n = 6 in each group) and glycolytic muscle (optical density: 1.03±0.03 in control vs. 0.65±0.04 after ligation, P< 0.05; n = 6 in each group). Additional immunofluorescence study demonstrates down-regulation of SOD in the ischemic hindlimb muscles. Second, the reflex blood pressure response to static muscle contraction was examined in control rats (n=5) and rats with 72 hours of femoral occlusion (n=6). The data show that the augmented reflex pressor response to muscle contraction was significantly attenuated after compensating SOD in ischemic muscles by chronic administration of tempol (a mimetic of SOD, 30 mg over a period of 72 hours) into the hindlimb. In the ligated rats, mean arterial pressure response was 26±3 mmHg with no tempol (n=6) and 12±2 mmHg with tempol application ( P< 0.05 vs. group with no tempol; n =5). Conclusions: Muscle SOD is blunted in the ischemic limbs and supplement of SOD mimetic for anti-oxidation improves the augmented blood pressure response during static exercise, which is beneficial to the restricted blood flow to the limbs in PAD patients.

scholarly journals Thermotherapy reduces blood pressure and circulating endothelin-1 concentration and enhances leg blood flow in patients with symptomatic peripheral artery disease

2016 ◽  
Vol 311 (2) ◽  
pp. R392-R400 ◽  
Author(s):  
Dustin Neff ◽  
Alisha M. Kuhlenhoelter ◽  
Chen Lin ◽  
Brett J. Wong ◽  
Raghu L. Motaganahalli ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Peripheral Artery Disease ◽  
Popliteal Artery ◽  
Peripheral Artery ◽  
Leg Blood Flow ◽  
Endothelin 1 ◽  
Control Intervention ◽  
Artery Disease ◽  
The Impact

Leg thermotherapy (TT) application reduces blood pressure (BP) and increases both limb blood flow and circulating levels of anti-inflammatory mediators in healthy, young humans and animals. The purpose of the present study was to determine the impact of TT application using a water-circulating garment on leg and systemic hemodynamics and on the concentrations of circulating cytokines and vasoactive mediators in patients with symptomatic peripheral artery disease (PAD). Sixteen patients with PAD and intermittent claudication (age: 63 ± 9 yr) completed three experimental sessions in a randomized order: TT, control intervention, and one exercise testing session. The garment was perfused with 48°C water for 90 min in the TT session and with 33°C water in the control intervention. A subset of 10 patients also underwent a protocol for the measurement of blood flow in the popliteal artery during 90 min of TT using phase-contrast MRI. Compared with the control intervention, TT promoted a significant reduction in systolic (∼11 mmHg) and diastolic (∼6 mmHg) BP ( P < 0.05) that persisted for nearly 2 h after the end of the treatment. The serum concentration of endothelin-1 (ET-1) was significantly lower 30 min after exposure to TT (Control: 2.3 ± 0.1 vs. TT: 1.9 ± 0.09 pg/ml, P = 0.026). In addition, TT induced a marked increase in peak blood flow velocity (∼68%), average velocity (∼76%), and average blood flow (∼102%) in the popliteal artery ( P < 0.01). These findings indicate that TT is a practical and effective strategy to reduce BP and circulating ET-1 concentration and enhance leg blood flow in patients with PAD.

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