Increase In Muscle Blood Flow Research Articles

Hemodynamic changes in the temporalis and masseter muscles during acute stress in healthy humans.

Autonomic control of orofacial areas is an integral part of the stress response, controlling functions such as pupil dilatation, salivation, and skin blood flow. However, the specific control of blood flow in head muscles during stress is unknown. This study aims to investigate the hemodynamic response of temporalis and masseter muscles in response to five different stressors. Sixteen healthy individuals were subjected to a randomized series of stressors, including cold pressor test, mental arithmetic test, apnea, isometric handgrip, and post-handgrip muscle ischemia, while in the sitting posture. Finger-pulse photoplethysmography was used to measure arterial blood pressure, heart rate, and cardiac output. Near-infrared spectroscopy was used to measure changes in tissue oxygenation and hemoglobin indices from the temporalis and masseter muscles. All stressors effectively and significantly increased arterial blood pressure. Tissue oxygenation index significantly increased in both investigated head muscles during mental arithmetic test (temporalis: 4.22 ± 3.52%; masseter: 3.43 ± 3.63%) and isometric handgrip (temporalis: 3.45 ± 3.09%; masseter: 3.26 ± 3.07%), suggesting increased muscle blood flow. Neither the masseter nor the temporalis muscles evidenced a vasoconstrictive response to any of the stressors tested. In the different conditions, temporalis and masseter muscles exhibited similar hemodynamic patterns of response, which do not include the marked vasoconstriction generally observed in limb muscles. The peculiar sympathetic control of head muscles is possibly related to the involvement of these muscles in aggressive/defensive reactions and/or to their unfavorable position with regard to hydrostatic blood levels.

Benefits of sauna on lung capacity, neurocognitive diseases, and heart health

Sauna refers to passive heat therapy that involves exposure of the body to a high-temperature environment for an appropriately short period, contingent on the therapy’s purpose. Ideally, the therapy aims to raise the internal body temperature by a few degrees, and its effect happens in two phases. The first phase occurs during the first ten minutes, encouraging the body to perspire while maintaining a temperature of around 98.6 degrees. The extra heat is dispersed by increased blood circulation, blood pushing on the skin's surface, and sweating. The body enters the second phase after 10-30 minutes in the sauna. During this period, the body cannot disperse the sauna heat, thereby increasing the body temperature. In return, the heart rate and sweating increase. There are four different types of saunas. These include traditional saunas, usually heated with wood-burning stoves, rocks, or an electric coil. Far-infrared saunas are usually heated by metallic or ceramic elements that produce a small spectrum of light, referred to as far-infrared. Infrared lamp saunas are heated using heat lamps that produce radiant heat. The last type is steam saunas, traditionally heated, but water increases the humidity and air temperatures. During sauna therapy, the heart rate of an individual increase from the standard range up to 120 or 150 beats per minute. Unlike physical activity, sauna therapy does not involve any active function of the skeletal muscles. Even though skeletal muscles are inactive during a sauna session, blood volume is partially redirected to the internal organs' exterior body parts due to decreased venous return. Sauna therapy assists in liberating toxins piled in our tissues, facilitating lymph and blood circulation and strengthening one's immune system. Sauna bathing has mainly been used for purposes of relaxation and pleasure. Today, the activity is increasingly becoming popular as a form of treatment therapy. Several pieces of evidence claim that sauna bathing has numerous health benefits, including hemodynamic regulation processes, reduced risk of vascular diseases, cardiovascular disease, neurocognitive diseases, mortality, pulmonary diseases, stabilized arterial blood pressure, and enhancement of conditions such as flu, headache, and arthritis. However, response to stress from heat can increase muscle blood flow. This report will precisely explore the benefits of sauna bathing on lung capacity and heart health for people with cardiovascular, lung-related or respiratory-related, and neurocognitive diseases.

Does sympathetic vasoconstriction contribute to metabolism: Perfusion matching in exercising skeletal muscle?

The process of matching skeletal muscle blood flow to metabolism is complex and multi-factorial. In response to exercise, increases in cardiac output, perfusion pressure and local vasodilation facilitate an intensity-dependent increase in muscle blood flow. Concomitantly, sympathetic nerve activity directed to both exercising and non-active muscles increases as a function of exercise intensity. Several studies have reported the presence of tonic sympathetic vasoconstriction in the vasculature of exercising muscle at the onset of exercise that persists through prolonged exercise bouts, though it is blunted in an exercise-intensity dependent manner (functional sympatholysis). The collective evidence has resulted in the current dogma that vasoactive molecules released from skeletal muscle, the vascular endothelium, and possibly red blood cells produce local vasodilation, while sympathetic vasoconstriction restrains vasodilation to direct blood flow to the most metabolically active muscles/fibers. Vascular smooth muscle is assumed to integrate a host of vasoactive signals resulting in a precise matching of muscle blood flow to metabolism. Unfortunately, a critical review of the available literature reveals that published studies have largely focused on bulk blood flow and existing experimental approaches with limited ability to reveal the matching of perfusion with metabolism, particularly between and within muscles. This paper will review our current understanding of the regulation of sympathetic vasoconstriction in contracting skeletal muscle and highlight areas where further investigation is necessary.

Evaluation of Local Skeletal Muscle Blood Flow in Manipulative Therapy by Diffuse Correlation Spectroscopy.

Manipulative therapy (MT) is applied to motor organs through a therapist’s hands. Although MT has been utilized in various medical treatments based on its potential role for increasing the blood flow to the local muscle, a quantitative validation of local muscle blood flow in MT remains challenging due to the lack of appropriate bedside evaluation techniques. Therefore, we investigated changes in the local blood flow to the muscle undergoing MT by employing diffuse correlation spectroscopy, a portable and emerging optical measurement technology that non-invasively measures blood flow in deep tissues. This study investigated the changes in blood flow, heart rate, blood pressure, and autonomic nervous activity in the trapezius muscle through MT application in 30 volunteers without neck and shoulder injury. Five minutes of MT significantly increased the median local blood flow relative to that of the pre-MT period (p < 0.05). The post-MT local blood flow increase was significantly higher in the MT condition than in the control condition, where participants remained still without receiving MT for the same time (p < 0.05). However, MT did not affect the heart rate, blood pressure, or cardiac autonomic nervous activity. The post-MT increase in muscle blood flow was significantly higher in the participants with muscle stiffness in the neck and shoulder regions than in those without (p < 0.05). These results suggest that MT could increase the local blood flow to the target skeletal muscle, with minimal effects on systemic circulatory function.

Effects of the exercise training on skeletal muscle oxygen consumption in heart failure patients with reduced ejection fraction

AimsSkeletal muscle dysfunction is a systemic consequence of heart failure (HF) that correlates with functional capacity. However, the impairment within the skeletal muscle is not well established. We investigated the effect of exercise training on peripheral muscular performance and oxygenation in HF patients. Methods and resultsHF patients with ejection fraction ≤40% were randomized 2:1 to exercise training or control for 12 weeks. Muscle tissue oxygen was measured noninvasively by near-infrared spectroscopy (NIRS) during rest and a symptom-limited cardiopulmonary exercise test (CPET) before and after intervention. Measurements included skeletal muscle oxygenated hemoglobin concentration, deoxygenated hemoglobin concentration, total hemoglobin concentration, VO2 peak, VE/VCO2 slope, and heart rate. Muscle sympathetic nerve activity by microneurography, and muscle blood flow by plethysmography were also assessed at rest pre and post 12 weeks. Twenty-four participants (47.5 ± 7.4 years, 58% men, 75% no ischemic) were allocated to exercise training (ET, n = 16) or control (CG, n = 8). At baseline, no differences between groups were found. Exercise improved VO2 peak, slope VE/VCO2, and heart rate. After the intervention, significant improvements at rest were seen in the ET group in muscle sympathetic nerve activity and muscle blood flow. Concomitantly, a significant decreased in Oxy-Hb (from 29.4 ± 20.4 to 15.7 ± 9.0 μmol, p = 0.01), Deoxi-Hb (from 16.3 ± 8.2 to 12.2 ± 6.0 μmol, p = 0.003) and HbT (from 45.7 ± 27.6 to 27.7 ± 13.4 μmol, p = 0.008) was detected at peak exercise after training. No changes were observed in the control group. ConclusionExercise training improves skeletal muscle function and functional capacity in HF patients with reduced ejection fraction. This improvement was associated with increased oxygenation of the peripheral muscles, increased muscle blood flow, and decreased sympathetic nerve activity.

Givinostat as metabolic enhancer reverting mitochondrial biogenesis deficit in Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is a rare disorder characterized by progressive muscle wasting, weakness, and premature death. Remarkable progress has been made in genetic approaches, restoring dystrophin, or its function. However, the targeting of secondary pathological mechanisms, such as increasing muscle blood flow or stopping fibrosis, remains important to improve the therapeutic benefits, that depend on tackling both the genetic disease and the downstream consequences. Mitochondrial dysfunctions are one of the earliest deficits in DMD, arise from multiple cellular stressors and result in less than 50% of ATP content in dystrophic muscles. Here we establish that there are two temporally distinct phases of mitochondrial damage with depletion of mitochondrial mass at early stages and an accumulation of dysfunctional mitochondria at later stages, leading to a different oxidative fibers pattern, in young and adult mdx mice. We also observe a progressive mitochondrial biogenesis impairment associated with increased deacetylation of peroxisome proliferator-activated receptor-gamma coactivator 1 α (PGC-1α) promoter. Such histone deacetylation is inhibited by givinostat that positively modifies the epigenetic profile of PGC-1α promoter, sustaining mitochondrial biogenesis and oxidative fiber type switch. We, therefore, demonstrate that givinostat exerts relevant effects at mitochondrial level, acting as a metabolic remodeling agent capable of efficiently promoting mitochondrial biogenesis in dystrophic muscle.

Teaching Cardiovascular Effects of Exercise Using an Integrated Model of the Cardiovascular System

Previously, a teaching model was developed to encompass cardiovascular concepts, including but not limited to venous capacitance, filling pressure (preload), and control of arterial and venous tone (1). The model was designed to articulate integrated cardiovascular responses in multiple physiologic and pathophysiologic conditions. From personal experience, students often assume that since sympathetic stimulation increases during exercise, total peripheral resistance (TPR) must also increase. This reflects a misunderstanding of the magnitude of the role of autoregulatory vasodilation in increasing muscle blood flow during exercise (2). It also reflects a lack of appreciation in the interplay of metabolic demand and the baroreceptor reflex as key factors controlling cardiac output. We use the model to show the following: the initial response to exercise is muscular autoregulatory vasodilation, leading to a decrease in TPR; decreases in TPR may initially decrease mean arterial pressure (MAP) (3); reduction in MAP reduces baroreceptor action potentials, resulting in increased sympathetic activity, including non-muscular vasoconstriction and venoconstriction; venoconstriction mobilizes the blood stored in the venous system (capacitance); blood mobilized by venoconstriction helps to maintain filling pressure (preload) and also satisfies the increased demand for blood by the exercising muscles; increases in sympathetic tone increase the inotropic, chronotropic, and lusitropic states of the heart, and; the consequent increase in cardiac output chiefly results from the interaction of systemic vasodilation in response to metabolic demand and the response of the baroreceptor reflex. This teaching model helps emphasize the importance of autoregulation to meet metabolic needs. It also illustrates the importance of sympathetic venoconstriction in maintaining filling pressure in diverse physiological and pathophysiologic conditions. Finally, it helps students understand that cardiac output is primarily regulated in response to tissue demand, as well as how this may occur. Understanding the normal response to exercise helps the student to recognize abnormal responses in pathophysiologic conditions, such as hypertension (4). References Jawad R., McCabe R. FASEB J 34(Supp1):1 (2020) Laughlin MH. Am J. Physiol 277 (Adv Physiol Educ 22): S244–S259 (1999) Guyton A. Circulation.64 1079-1088 (1981) Kim D., Ha JW. Clin Hypertens 22, 17 (2016)

A comparison of moist heat, dry heat, chemical dry heat and icy hot for deep tissue heating and changes in tissue blood flow.

Background: Intermittent bouts of heavy activity at greater than normal exercise intensity can cause delayed onset muscle soreness (DOMS). Several products are commercially available, all alleging to reduce DOMS. In the present investigation, 40 subjects (average age 27.0+/-4.4 years, average BMI 26.8) were assessed to determine the effect of 4 of these products on skin and muscle temperature and blood flow during 2 hours of application. These included ThermaCare Dry Heat Wraps, ThermaCare Moist Heat Wraps, Icy Hot Patches, and hydrocollator heat packs. Methods; Blood flow was measured (by laser doppler flow meter) over and in the quadriceps muscle and tissue temperature was measured (by thermistors and thermocouples) in these same areas. Results: The results of the study indicated that only ThermaCare Dry and Moist Heat Wraps both heated the muscle and increased muscle blood flow. The menthol and methyl salicylate compounds in Icy Hot cooled muscle. Skin blood flow increased 300% after the moist heat was applied after 45 minutes, low level continuous dry heat almost 256% but it took 105 minutes to reach this flow, hydrocollator heat wraps increased by 201% but only for only first 45 minutes and then back to baseline, a slight reduction in skin blood flow was seen with Icy Hot gel applied to the skin. Moist heat caused muscle temperature to increase by an average of 3.1 Deg C. Dry heat caused muscle temperature to increase by 2.2 Deg C, while hydrocollator packs increased temperature by 0.4 Deg C. Icy hot had no effect on muscle temperature. Conclusion: Continuous low level heat products had better penetration into muscle and increased blood flow the best compared to hydrocollator heat packs and Icy Hot patches.

Artificial Co 2 -water Immersion Facilitates Recovery From Muscle Fatigue Caused By High Intensity Anaerobic Exercise

In response to the CO2-water (CO2≥1000 ppm) immersion, the reduction of sympathetic nerve activity may imply the facilitation of muscle fatigue recovery. PURPOSE: In the present study, we investigated whether the whole body bath with CO2-water influences recovery of the muscle fatigue after high intensity exercise. METHODS: The healthy male college students (n=6, 18-21yrs, 171.3±6.7cm, 73.6±13.0kg) participated in this study. The cycle ergometer work tests lasting 30 seconds were used to estimate anaerobic power with leg pedaling exercises. Exercise loads of the tests were 0.075kp per body weight. Anaerobic power was determined by measuring the highest power output during 30 seconds. Core temperature (CoreT) and ECG were recorded continuously throughout the experiment. The subjects performed 30-s maximal pedaling exercise, and took bath in tap- or CO2-water at 35 °C for 10 minute after exercise. Subjective thermal sensation (TS) in the body bath was also recorded. Vastus lateralis (VL) dominant muscle hardness using the elastography. , muscle pain by visual analog scale (VAS), and blood lactate (BLa) and were evaluated at pre- and immediately after-exercise, and at 10 min after exercise. RESULTS: The strain ratio (SR) between the VL and a reference material was calculated. TS in the CO2-water was significantly higher than in the tap-water (tap-water vs. CO2-water, -0.17±0.76 vs. 1.17±0.41, p<0.01). At 10 min in recovery, in the CO2-water compared with the tap-water, SR significantly decreased quicker (0.49±0.25 vs. 0.91±0.25, p<0.01). However, there was no significant difference in CoreT, BLa and VAS between these two water kinds. CONCLUSIONS: We reported previously that the muscle blood flow in the immersed part was larger in CO2-water than tap-water of a same temperature. In addition to a local effect of CO2, suppression of muscular sympathetic activity may also contribute to the increase in local blood flow. Facilitation of muscle hardness recovery shown in this study might be caused by the increased muscle blood flow. The present results suggested that CO2-water immersion may contribute to rapid recovery from the muscular hardness induced by high intensity exercise.

Impact of Active Recovery and Whole-Body Electromyostimulation on Blood-Flow and Blood Lactate Removal in Healthy People.

This study aimed to determine whether an active recovery with added whole-body electromyostimulation (WB-EMS) can increase blood flow and lead to blood lactate removal after intense exercise. Thirty-five healthy individuals (23.1 ± 4.6 years) were randomly assigned to: (a) an experimental group using active recovery together with the WB-EMS (n = 18) or (b) a control group using the same active recovery protocol with the suit with no-stimulation (CON, n = 17). Participants performed a maximal graded exercise test followed by an active recovery protocol (walking at 40% of their maximum aerobic velocity). During the recovery, participants in WB-EMS and CON received continuous stimulation at 7 Hz or no stimulation, respectively. Heart rate, blood lactate concentrations, pain/discomfort, and hemodynamic measurements were recorded before and after the test, and repeated immediately after and at min 30 and 60. The between-group analysis showed a substantially greater Peak blood velocity (−0.27 [−0.68; 0.14]) in WB-EMS compared to CON. The pain/discomfort levels were also lower in WB-EMS compared with CON (0.66 [−0.12; 1.45]). Non-significant differences in participants’ blood lactate were observed in WB-EMS compared with CON both immediately; at 30and 60 min. Our findings suggest that increased local blood flow induced by WB-EMS may have contributed to greater lactate removal from active muscles and blood lactate clearance. WB-EMS may be an effective means of increasing muscle blood flow after a maximal graded exercise test and could result in improved recovery.

Hyperinsulinemic Microvascular Blood Flow Response in Skeletal Muscle is Oxygen Mediated

ObjectiveTo determine if the blood flow response to insulin is partially mediated by local metabolic demand reflecting increased oxygen consumption required to fix glucose.MethodsTwo separate protocols were used to address the objective. 8 Sprague‐Dawley (171–204g) rats, 4 per protocol, were anesthetized with sodium pentobarbital via intraperitoneal injection, and mechanically ventilated. Arterial and venous catheters were introduced to maintain and monitor the animals’ cardiovascular state. The extensor digitorum longus (EDL) muscle was isolated and reflected onto the stage of an Olympus IX73 inverted microscope. Intravital video microscopy sequences were recorded during baseline and at hyperinsulinemic euglycemia in both protocols. Euglycemia was achieved through intravenous infusion of 2U insulin/kg/hr and variable rates of 50% D‐glucose were titrated against repeated blood glucose samples until stable normoglycemic levels were reached. In protocol 1, the EDL was reflected over a glass stage insert and isolated from room air with polyvinylidene film and a glass coverslip. In protocol 2, the muscle was instead reflected over a 100μm thick semi‐permeable membrane interfacing the EDL with a gas exchange chamber and similarly isolated from room air. An oxygen (O2) challenge was imposed in protocol 2 where O2 levels were oscillated at one minute intervals from 7%‐12%‐2%‐7%, with a stable 5% carbon dioxide concentration and the balance of gas composed of nitrogen. For both protocols, offline analysis of microvascular flow was conducted using custom MATLAB software yielding frame‐by‐frame measurements of capillary red blood cell (RBC) velocity, hematocrit, RBC supply rate (SR), and oxygen saturation (SO2). Animal protocols were approved by Memorial University’s Institutional Animal Care Committee.ResultsNo significant changes were found between glucose infusion rates (GIR) at euglycemia between both protocols, as well as blood glucose levels at both baseline and euglycemic conditions between experiments. In protocol 1, SR increased to 11.2 cells/s following euglycemic clamp, compared to 8.0 cells/s at baseline (p = 0.0255) consistent with flow increases reported in the literature. As expected, the imposed O2 challenges in protocol 2 caused significant changes in SO2 at 12% and 2% concentrations, which were found to be the same under both baseline and euglycemic conditions. In protocol 2, SR decreased at 12% O2 and increased at 2% O2 during the oscillation, compared to 7% O2, under both baseline and euglycemic conditions. SR was the same under euglycemia compared to baseline in the last 15 seconds of each step of the O2 oscillation from 7%‐12%‐2%‐7%, with p values &gt;0.9999, &gt;0.9999, 0.9984, and 0.9963 respectively.ConclusionsGas exchange chamber was effective at manipulating tissue oxygen levels, observed through profound SO2 changes during chamber oscillations at both baseline and euglycemic conditions. Our results suggest that the increase in muscle blood flow observed in response to insulin, as seen in experiment 1, is eliminated if the tissue oxygen environment is fixed at a given oxygen concentration as demonstrated in experiment 2.Support or Funding InformationProject funded through a CIHR project grant awarded to GM Fraser (PJT‐162119)Time series showing the change in capillary red blood cell oxygen saturation over the imposed oxygen oscillations under baseline and hyperinsulinemic euglycemic conditions (N=4 animals, 52 capillaries).Figure 1Time series of capillary red blood cell supply rate response to imposed oxygen oscillations under baseline and hyperinsulinemic euglycemic conditions (N=4 animals, 135 capillaries).Figure 2

Contribution of KIR Channels and the Na+/K+‐ATPase to Local Vasodilation During Mild and Heavy Intensity Exercise in Humans

Potassium released from repolarizing skeletal muscle elicits vasodilation by stimulating inwardly‐rectifying K+ (KIR) channels and the Na+/K+‐ATPase on the vasculature, which can serve as a feedforward mechanism to increase muscle blood flow in proportion to the degree of muscle fiber recruitment during exercise. We tested the hypothesis that KIR channels and the Na+/K+‐ATPase play a greater role in the vasodilatory response to exercise at higher contraction intensities which require greater muscle fiber recruitment. Healthy volunteers performed mild and heavy intensity rhythmic handgrip exercise using a dynamic pulley system to lift a load equivalent to 10% or 25% of maximal voluntary contraction (MVC) at a rate of 20 contractions per minute. We measured muscle activation (electromyography; EMG), forearm blood flow (FBF; Doppler ultrasound) and mean arterial pressure (MAP; brachial artery catheter) to calculate vascular conductance (FVC; FBF/MAP*100) during 5 min of forearm exercise at each intensity. Responses were assessed during 1) control conditions, 2) local inhibition of either KIR channels alone (Protocol 1; intra‐arterial BaCl2) or the Na+/K+‐ATPase alone (Protocol 2; intra‐arterial ouabain; OUA), and 3) combined inhibition of KIR channels and the Na+/K+‐ATPase (Protocols 1 &amp; 2; BaCl2 + OUA). As expected, muscle activation was greater during heavy compared to mild exercise (Control EMG, 65 ± 6 vs. 32 ± 3% of MVC; P &lt; 0.05). In Protocol 1 (4 women, 5 men; 26 ± 1 yrs), BaCl2 reduced steady‐state FVC by −62 ± 21 ml/min/100 mmHg during mild exercise (Control: 170 ± 27 vs. BaCl2: 107 ± 10 ml/min/100 mmHg; P &lt; 0.05), and combined inhibition with BaCl2 + OUA had no further effect (Δ FVC from Control, −67 ± 20; FVC, 103 ± 11 ml/min/100 mmHg; P = NS vs. BaCl2 alone). During heavy intensity exercise, BaCl2 reduced FVC by −59 ± 13 ml/min/100 mmHg (Control: 333 ± 24 vs. BaCl2: 274 ± 29 ml/min/100 mmHg; P &lt; 0.05), which was similar to the effect of BaCl2 during mild exercise (Δ FVC P = NS vs. mild exercise). However, in contrast to mild exercise, combined inhibition with BaCl2 + OUA further attenuated FVC during heavy intensity exercise (Δ FVC from Control, □108 ± 24; FVC, 225 ± 15 ml/min/100 mmHg; P &lt; 0.05 vs. BaCl2). In Protocol 2 (2 women, 3 men; 26 ± 2 yrs), OUA alone had no effect on FVC during mild exercise (Δ FVC from Control, −2 ± 6; FVC, Control: 141 ± 31 vs. OUA: 139 ± 36; P = NS) or heavy exercise (Δ FVC from Control, −11 ± 11; FVC, Control: 325 ± 70 vs. OUA: 313 ± 71; P = NS), whereas combined inhibition with BaCl2 + OUA reduced FVC to a similar extent as in Protocol 1 (mild exercise, Δ FVC from Control: −43 ± 4; FVC: 98 ± 30; heavy exercise, Δ FVC from Control: −109 ± 16; FVC: 216 ± 66 ml/min/100 mmHg, both P &lt; 0.05 vs. Control and OUA alone). We conclude that KIR channel activation contributes similarly to skeletal muscle vascular tone at mild and heavy exercise intensities. Furthermore, an obligatory role for Na+/K+‐ATPase in vascular control is not revealed until KIR channels are inhibited during heavy intensity exercise.Support or Funding InformationNIH R01‐HL119337

Nitrate uptake and metabolism in human skeletal muscle cell cultures

Several studies show that dietary nitrate enhances exercise performance, presumably by increasing muscle blood flow and improving oxygen utilization. These effects are likely mediated by nitrate metabolites, including nitrite and nitric oxide (NO). However, the mechanisms of nitrate production, storage, and metabolism to nitrite and NO in skeletal muscle cells are still unclear. We hypothesized that exogenous nitrate can be taken up and metabolized to nitrite/NO inside the skeletal muscle. We found rapid uptake of exogeneous nitrate in both myoblasts and myotubes, increasing nitrite levels in myotubes, but not myoblasts. During differentiation we found increased expression of molybdenum containing proteins, such as xanthine oxidoreductase (XOR) and the mitochondrial amidoxime-reducing component (MARC); nitrate and nitrite reductases. Sialin, a known nitrate transporter, was detected in myoblasts; nitrate uptake decreased after sialin knockdown. Inhibition of chloride channel 1 (CLC1) also led to significantly decreased uptake of nitrate. Addition of exogenous nitrite, which resulted in higher intracellular nitrite levels, increased intracellular cGMP levels in myotubes. In summary, our results demonstrate for the first time the presence of the nitrate/nitrite/NO pathway in skeletal muscle cells, namely the existence of strong uptake of exogenous nitrate into cells and conversion of intracellular nitrate to nitrite and NO. Our results further support our previously formulated hypothesis about the importance of the nitrate to nitrite to NO intrinsic reduction pathways in skeletal muscles, which likely contributes to improved exercise tolerance after nitrate ingestion.

Somatosensory regulation of resting muscle blood flow and physical therapy.

Somatosensory stimulation can affect skeletal muscle blood flow (MBF) at rest in anesthetized animals via pressor reflex response or antidromic and local vasodilation. Increase in MBF due to reflex pressor response occurs generally in the skeletal muscles of the entire body, while antidromic and local vasodilation are limited to the peripheral stimulation site. Since increased MBF improves several disorders (muscle stiffness, pain, etc.), it is reasonable to further explore the effective use of somatic stimulation in physical therapies, such as massage, acupuncture, anma, and shiatsu or acupressure, in treating skeletal muscle disorders.

Exercise Training Increases Metaboreflex Control in Patients with Obstructive Sleep Apnea.

We demonstrated that patients with obstructive sleep apnea (OSA) have reduced muscle metaboreflex control of muscle sympathetic nerve activity (MSNA). In addition, exercise training increased muscle metaboreflex control in heart failure patients. We tested the hypothesis that exercise training would increase muscle metaboreflex control of MSNA in patients with OSA. Forty-one patients with OSA were randomized into the following two groups: 1) nontrained (OSANT, n = 21) and 2) trained (OSAT, n = 20). Muscle sympathetic nerve activity was assessed by microneurography technique, muscle blood flow (FBF) by venous occlusion plethysmography, heart rate by electrocardiography, and blood pressure with an automated oscillometric device. All physiological variables were simultaneously assessed at rest, during isometric handgrip exercise at 30% of the maximal voluntary contraction, and during posthandgrip muscle ischemia (PHMI). Muscle metaboreflex sensitivity was calculated as the difference in MSNA between PHMI and the rest period. Patients in the OSAT group underwent 72 sessions of moderate exercise training, whereas patients in the OSANT group were clinical follow-up for 6 months. The OSANT and OSAT groups were similar in anthropometric, neurovascular, hemodynamic and sleep parameters. Exercise training reduced the baseline MSNA (34 ± 2 bursts per minute vs 25 ± 2 bursts per minute; P < 0.05) and increased the baseline FBF (2.1 ± 0.2 mL·min per 100 g vs 2.4 ± 0.2 mL·min per 100 g; P < 0.05). Exercise training significantly reduced MSNA levels and increased FBF responses during isometric exercise. Exercise training significantly increased MSNA responses during PHMI (Δ6.5 ± 1 vs -1.7 ± 1 bursts per minute, P < 0.01). No significant changes in FBF or hemodynamic parameters in OSANT patients were found. Exercise training increases muscle metaboreflex sensitivity in patients with OSA. This autonomic change associated with increased muscle blood flow may contribute to the increase in exercise performance in this set of patients.

Phenylephrine increases near-infrared spectroscopy determined muscle oxygenation during head-up tilt in men

Phenylephrine is an α-adrenergic agent and yet seems to increase near-infrared spectroscopy determined muscle oxygenation (SmO2) that reflects the ratio between oxygenated (O2Hb) and deoxygenated (Hb) haemoglobin/myoglobin. We examined whether the increase in SmO2 by phenylephrine reflects veno-constriction and to secure filling of the veins, subjects were exposed to head-up tilt (HUT). Phenylephrine (0.2 mg) was administered to 10 healthy males (24 years (22–27; median with interquartile range)) during 40° HUT with SmO2, O2Hb and Hb determined for the biceps brachii and vastus lateralis muscles. Changes in red cell volume within the thorax and thigh were evaluated by electrical admittance and brachial vein diameter determined by ultrasound. HUT accumulated blood in arms and legs as indicated by reduced thoracic and conversely enhanced thigh electrical admittance. Both over the arm and leg, HUT reduced SmO2 as a consequence of reduced O2Hb and increased Hb (p < .05). After 5 min HUT, phenylephrine increased MAP and total peripheral resistance, and both arm and thigh SmO2 increased due to a decrease in Hb and an increase in O2Hb. The results confirm that SmO2 decreases during HUT and demonstrate venous filling in the limbs. Furthermore, vasoconstriction during HUT is indicated by a decrease in O2Hb. Conversely, phenylephrine increased SmO2 likely illustrating increased muscle blood flow and venoconstriction as O2Hb increased while Hb was reduced.

Effect of leg immersion in mild warm carbonated water on skin and muscle blood flow.

Leg immersion in carbonated water improves endothelial‐mediated vasodilator function and decreases arterial stiffness but the mechanism underlying this effect remains poorly defined. We hypothesized that carbonated water immersion increases muscle blood flow. To test this hypothesis, 10 men (age 21 ± 0 years; mean ± SD) underwent lower leg immersion in tap or carbonated water at 38°C. We evaluated gastrocnemius muscle oxyhemoglobin concentration and tissue oxygenation index using near‐infrared spectroscopy, skin blood flow by laser Doppler flowmetry, and popliteal artery (PA) blood flow by duplex ultrasound. Immersion in carbonated, but not tap water elevated PA (from 38 ± 14 to 83 ± 31 mL/min; P < 0.001) and skin blood flow (by 779 ± 312%, P < 0.001). In contrast, lower leg immersion elevated oxyhemoglobin concentration and tissue oxygenation index with no effect of carbonation (P = 0.529 and P = 0.495). In addition, the change in PA blood flow in response to immersion in carbonated water correlated with those of skin blood flow (P = 0.005) but not oxyhemoglobin concentration (P = 0.765) and tissue oxygenation index (P = 0.136) while no relations was found for tap water immersion. These findings indicate that water carbonation has minimal effect on muscle blood flow. Furthermore, PA blood flow increases in response to lower leg immersion in carbonated water likely due to a large increase in skin blood flow.

NaV1.9 channels in muscle afferent neurons and axons.

The exercise pressor reflex (EPR) is activated by muscle contractions to increase heart rate and blood pressure during exercise. While this reflex is beneficial in healthy individuals, the reflex activity is exaggerated in patients with cardiovascular disease, which is associated with increased mortality. Group III and IV afferents mediate the EPR and have been shown to express both tetrodotoxin-sensitive (TTX-S, NaV1.6, and NaV1.7) and -resistant (TTX-R, NaV1.8, and NaV1.9) voltage-gated sodium (NaV) channels, but NaV1.9 current has not yet been demonstrated. Using a F--containing internal solution, we found a NaV current in muscle afferent neurons that activates at around -70 mV with slow activation and inactivation kinetics, as expected from NaV1.9 current. However, this current ran down with time, which resulted, at least in part, from increased steady-state inactivation since it was slowed by both holding potential hyperpolarization and a depolarized shift of the gating properties. We further show that, following NaV1.9 current rundown (internal F-), application of the NaV1.8 channel blocker A803467 inhibited significantly more TTX-R current than we had previously observed (internal Cl-), which suggests that NaV1.9 current did not rundown with that internal solution. Using immunohistochemistry, we found that the majority of group IV somata and axons were NaV1.9 positive. The majority of small diameter myelinated afferent somata (putative group III) were also NaV1.9 positive, but myelinated muscle afferent axons were rarely labeled. The presence of NaV1.9 channels in muscle afferents supports a role for these channels in activation and maintenance of the EPR. NEW & NOTEWORTHY Small diameter muscle afferents signal pain and muscle activity levels. The muscle activity signals drive the cardiovascular system to increase muscle blood flow, but these signals can become exaggerated in cardiovascular disease to exacerbate cardiac damage. The voltage-dependent sodium channel NaV1.9 plays a unique role in controlling afferent excitability. We show that NaV1.9 channels are expressed in muscle afferents, which supports these channels as a target for drug development to control hyperactivity of these neurons.

Artificial CO2-water Leg-bath Facilitates Recovery From Muscle Hardness Caused By Resistance Exercise

Facilitation of the blood stream and oxygen consumption of the muscle by a local immersion of the extremities into high concentration carbon dioxide water (CO2-water, CO2≥1000ppm), suggests an improvement of muscle performance and joints flexibility. PURPOSE: In the present study, we investigated whether the immersion of extremities including agonist muscles into artificially made CO2-water influenced recovery of the increased muscle hardness induced by a resistance exercise. METHODS: The healthy male college students (n=11, age; 18-19 yrs, height; 168.6±4.5 cm, weight; 66.2±9.3 kg) participated in this study. The subjects performed 100 times calf raise resistance exercise and immersed lower legs into tap-water or artificial CO2-water at 35 °C for 10 minutes immediately after the exercise. Blood flow in the immersed skin (BFskin) and electrocardiogram (ECG) were recorded continuously throughout the experiment. Hardness of the gastrocnemius medialis (MG) was evaluated using ultrasound real-time tissue elastography. Visual analog scale test on muscle pain (VAS) and muscle hardness measurements were performed at 3 time points (prior to exercise, immediately after exercise, at 10 min after exercise). The strain ratio (SR) between the MG and a reference material was calculated. RESULTS: BFskin in the CO2-water leg-bath was significantly higher than that in the tap-water leg-bath (CO2 -water vs. tap-water, 5.5±1.8 vs. 2.1±1.2 ml·min-1·100g-1, p<0.05). At 10 min after exercise, CO2 -water treatment compared with the tap-water treatment, SR decreased significantly quicker (1.37±0.28 vs. 0.67±0.08, p<0.05). In addition, VAS at recovery 10 min became smaller in the CO2-water than the tap-water (18.1±10.2 vs. 33.9±16.2 mm, p<0.05). CONCLUSIONS: We reported previously that the muscle blood flow in the immersed part was larger in CO2-water than tap-water of a same temperature. In addition to a local effect of CO2, suppression of muscular sympathetic activity may also contribute to the increase in local blood flow. Facilitation of muscle hardness recovery shown in this study might be caused by the increased muscle blood flow. The present study suggested that high concentration artificial CO2-water immersion may contribute to rapid recovery from the high intensity exercise-induced muscle fatigue.

Daily muscle stretching enhances blood flow, endothelial function, capillarity, vascular volume and connectivity in aged skeletal muscle.

In aged rats, daily muscle stretching increases blood flow to skeletal muscle during exercise. Daily muscle stretching enhanced endothelium-dependent vasodilatation of skeletal muscle resistance arterioles of aged rats. Angiogenic markers and capillarity increased in response to daily stretching in muscles of aged rats. Muscle stretching performed with a splint could provide a feasible means of improving muscle blood flow and function in elderly patients who cannot perform regular aerobic exercise. Mechanical stretch stimuli alter the morphology and function of cultured endothelial cells; however, little is known about the effects of daily muscle stretching on adaptations of endothelial function and muscle blood flow. The present study aimed to determine the effects of daily muscle stretching on endothelium-dependent vasodilatation and muscle blood flow in aged rats. The lower hindlimb muscles of aged Fischer rats were passively stretched by placing an ankle dorsiflexion splint for 30minday-1 , 5daysweek-1 , for 4weeks. Blood flow to the stretched limb and the non-stretched contralateral limb was determined at rest and during treadmill exercise. Endothelium-dependent/independent vasodilatation was evaluated in soleus muscle arterioles. Levels of hypoxia-induced factor-1α, vascular endothelial growth factor A and neuronal nitric oxide synthase were determined in soleus muscle fibres. Levels of endothelial nitric oxide synthase and superoxide dismutase were determined in soleus muscle arterioles, and microvascular volume and capillarity were evaluated by microcomputed tomography and lectin staining, respectively. During exercise, blood flow to plantar flexor muscles was significantly higher in the stretched limb. Endothelium-dependent vasodilatation was enhanced in arterioles from the soleus muscle from the stretched limb. Microvascular volume, number of capillaries per muscle fibre, and levels of hypoxia-induced factor-1α, vascular endothelial growth factor and endothelial nitric oxide synthase were significantly higher in the stretched limb. These results indicate that daily passive stretching of muscle enhances endothelium-dependent vasodilatation and induces angiogenesis. These microvascular adaptations may contribute to increased muscle blood flow during exercise in muscles that have undergone daily passive stretch.