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 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.

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.

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 Genetic Variation in Blood Pressure and Lifetime Risk of Peripheral Artery Disease: A Mendelian Randomization Study

2020 ◽  
Author(s):  
Michael G Levin ◽  
Derek Klarin ◽  
Venexia M Walker ◽  
Dipender Gill ◽  
Julie Lynch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Calcium Channel ◽  
Peripheral Artery Disease ◽  
Genetic Correlations ◽  
Channel Blockers ◽  
Peripheral Artery ◽  
Antihypertensive Medications ◽  
Increased Risk ◽  
Genes Encoding ◽  
Artery Disease

Aims: We aimed to estimate the effect of blood pressure and blood pressure lowering medications (via genetic proxies) on peripheral artery disease. Methods and Results: GWAS summary statistics were obtained for BP (International Consortium for Blood Pressure + UK Biobank GWAS; N = up to 757,601 individuals), peripheral artery disease (PAD; VA Million Veteran Program; N = 24,009 cases, 150,983 controls), and coronary artery disease (CAD; CARDIoGRAMplusC4D 1000 Genomes; N = 60,801 cases, 123,504 controls). Genetic correlations between systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and CAD and PAD were estimated using LD score regression. The strongest correlation was between SBP and CAD (rg = 0.36; p = 3.9 x 10-18). Causal effects were estimated by two-sample MR using a range of pleiotropy-robust methods. Increased SBP, DBP, and PP increased risk of both PAD (SBP OR 1.25 [1.19-1.31] per 10mmHg increase, p = 3 x 10-18; DBP OR 1.27 [1.17-1.39], p = 4 x 10-8; PP OR 1.51 [1.38-1.64], p = 1 x 10-20) and CAD (SBP OR 1.37 [1.29-1.45], p = 2 x 10-24; DBP OR 1.6 [1.45-1.76], p = 7 x 10-22; PP OR 1.56 [1.4-1.75], p = 1 x 10-15). The effects of SBP and DBP were greater for CAD than PAD (pdiff = 0.024 for SBP, pdiff = 4.9 x 10-4 for DBP). Increased liability to PAD increased PP (beta = 1.04 [0.62-1.45] mmHg per 1 unit increase in log-odds in liability to PAD, p = 1 x 10-6). MR was also used to estimate the effect of BP lowering through different classes of antihypertensive medications using genetic instruments containing BP-trait associated variants located within genes encoding protein targets of each medication. SBP lowering via calcium channel blocker-associated variants was protective of CAD (OR 0.38 per 10mmHg decrease in SBP; 95% CI 0.19-0.77; p = 0.007). Conclusions: Higher BP is likely to cause both PAD and CAD but may have a larger effect on CAD risk. BP-lowering through calcium-channel blockers (as proxied by genetic variants) decreased risk of CAD.

scholarly journals Eight weeks of nitrate supplementation improves blood flow and reduces the exaggerated pressor response during forearm exercise in peripheral artery disease

2018 ◽  
Vol 315 (1) ◽  
pp. H101-H108 ◽  
Author(s):  
Nicholas T. Kruse ◽  
Kenichi Ueda ◽  
William E. Hughes ◽  
Darren P. Casey
Keyword(s):  
Blood Flow ◽  
Peripheral Artery Disease ◽  
Pressor Response ◽  
Treated Group ◽  
Moderate Intensity ◽  
Peripheral Artery ◽  
Pressor Responses ◽  
Nitrate Supplementation ◽  
Artery Disease ◽  
Forearm Exercise

Peripheral artery disease (PAD) is characterized by a reduced blood flow (BF) and an elevated blood pressure (pressor) response during lower extremity exercise. Although PAD is evident in the upper extremities, no studies have determined BF and pressor responses during upper extremity exercise in PAD. Emerging evidence suggests that inorganic nitrate supplementation may serve as an alternative dietary strategy to boost nitric oxide bioavailability, improving exercising BF and pressor responses during exercise. The present study investigated 1) BF and pressor responses to forearm exercise in patients with PAD ( n = 21) relative to healthy age-matched control subjects ( n = 16) and 2) whether 8 wk of NaNO3 supplementation influenced BF and pressor responses to forearm exercise in patients with PAD. Patients with moderate to severe PAD were randomly assigned to a NaNO3 (1 g/day, n = 13)-treated group or a placebo (microcrystalline cellulose, n = 8)-treated group. Brachial artery forearm BF (FBF; via Doppler) and blood pressure (via finger plethysmography) were measured during mild-intensity (~3.5-kg) and moderate-intensity (~7-kg) handgrip exercise. The absolute change (from baseline) in FBF was reduced (except in the 3.5-kg condition) and BP responses were increased in patients with PAD compared with healthy control subjects in 3.5- and 7-kg conditions (all P < 0.05). Plasma nitrate and nitrite were elevated, exercising (7-kg) ΔFBF was improved (from 141 ± 17 to 172 ± 20 ml/min), and mean arterial pressure response was reduced (from 13 ± 1 to 9 ± 1 mmHg, P < 0.05) in patients with PAD that received NaNO3 supplementation for 8 wk relative to those that received placebo. These results suggest that the BF limitation and exaggerated pressor response to moderate-intensity forearm exercise in patients with PAD are improved with 8 wk of NaNO3 supplementation. NEW & NOTEWORTHY Peripheral artery disease (PAD) results in an exaggerated pressor response and reduced blood flow during lower limb exercise; however, the effect of PAD in the upper limbs has remained unknown. These results suggest that 8 wk of inorganic nitrate supplementation improves the blood flow limitation and exaggerated pressor response to moderate-intensity forearm exercise in PAD.

Vascular Inflammation, Calf Muscle Oxygen Saturation, and Blood Glucose are Associated With Exercise Pressor Response in Symptomatic Peripheral Artery Disease

Angiology ◽  
2019 ◽  
Vol 70 (8) ◽  
pp. 747-755 ◽  
Author(s):  
Andrew W. Gardner ◽  
Polly S. Montgomery ◽  
Ming Wang ◽  
Chixiang Chen ◽  
Marcos Kuroki ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Glucose ◽  
Oxygen Saturation ◽  
Peripheral Artery Disease ◽  
Pressor Response ◽  
Calf Muscle ◽  
Peripheral Artery ◽  
Muscle Oxygen ◽  
Artery Disease ◽  
Vascular Biomarkers

We determined whether calf muscle oxygen saturation (StO2) and vascular biomarkers of inflammation and oxidative stress were associated with an exercise pressor response during treadmill walking in 179 patients with symptomatic peripheral artery disease (PAD). The exercise pressor response was measured as the change in blood pressure from rest to the end of the first 2-minute treadmill stage (2 mph, 0% grade). There was a wide range in the change in systolic blood pressure (−46 to 50 mm Hg) and in diastolic blood pressure (−23 to 38 mm Hg), with mean increases of 4.3 and 1.4 mm Hg, respectively. In multiple regression analyses, significant predictors of systolic pressure included glucose ( P < .001) and insulin ( P = .039). Significant predictors of diastolic pressure included cultured endothelial cell apoptosis ( P = .019), the percentage drop in exercise calf muscle (StO2; P = .023), high-sensitivity C-reactive protein ( P = .032), and glucose ( P = .033). Higher levels in pro-inflammatory vascular biomarkers, impaired calf muscle StO2 during exercise, and elevated blood glucose were independently associated with greater exercise pressor response in patients with symptomatic PAD. The clinical implication is that exercise and nutritional interventions designed to improve inflammation, microcirculation, and glucose metabolism may also lower blood pressure during exercise in patients with symptomatic PAD.

Assessment of Coronary Artery Disease in Hemodialysis Patients with Delayed Systolic Blood Pressure Response after Exercise Testing

2005 ◽  
Vol 23 (6) ◽  
pp. 466-472 ◽  
Author(s):  
Masayoshi Fukui ◽  
Yasukiyo Mori ◽  
Kazuya Takehana ◽  
Hiroya Masaki ◽  
Masayuki Motohiro ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Systolic Blood Pressure ◽  
Exercise Testing ◽  
Blood Pressure Response ◽  
Hemodialysis Patients ◽  
Pressure Response ◽  
Artery Disease
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