Endothelin-1-mediated vasoconstriction at rest and during dynamic exercise in healthy humans

2007 ◽  
Vol 293 (4) ◽  
pp. H2550-H2556 ◽  
Author(s):  
D. Walter Wray ◽  
Steven K. Nishiyama ◽  
Anthony J. Donato ◽  
Mikael Sander ◽  
Peter D. Wagner ◽  
...  
Keyword(s):  
Blood Flow ◽  
Exercise Intensity ◽  
Muscle Blood Flow ◽  
Knee Extensor ◽  
Dynamic Exercise ◽  
Dependent Manner ◽  
Drug Infusion ◽  
Leg Blood Flow ◽  
Healthy Humans ◽  
Arterial Blood

It is now generally accepted that α-adrenoreceptor-mediated vasoconstriction is attenuated during exercise, but the efficacy of nonadrenergic vasoconstrictor pathways during exercise remains unclear. Thus, in eight young (23 ± 1 yr), healthy volunteers, we contrasted changes in leg blood flow (ultrasound Doppler) before and during intra-arterial infusion of the α1-adrenoreceptor agonist phenylephrine (PE) with that of the nonadrenergic endothelin A (ETA)/ETB receptor agonist ET-1. Heart rate, arterial blood pressure, common femoral artery diameter, and mean blood velocity were measured at rest and during knee-extensor exercise at 20%, 40%, and 60% of maximal work rate (WRmax). Drug infusion rates were adjusted for blood flow to maintain comparable doses across all subjects and conditions. At rest, PE infusion (8 ng·ml−1·min−1) provoked a rapid and significant decrease in leg blood flow (−51 ± 3%) within 2.5 min. Resting ET-1 infusion (40 pg·ml−1·min−1) significantly decreased leg blood flow within 5 min, reaching a maximal vasoconstriction (−34 ± 3%) after 25–30 min of continuous infusion. Compared with rest, an exercise intensity-dependent attenuation to PE-mediated vasoconstriction was observed (−18 ± 5%, −7 ± 2%, and −1 ± 3% change in leg blood flow at 20%, 40%, and 60% of WRmax, respectively). Vasoconstriction in response to ET-1 was also blunted in an exercise intensity-dependent manner (−13 ± 3%, −7 ± 4%, and 2 ± 3% change in leg blood flow at 20%, 40%, and 60% of WRmax, respectively). These findings support a significant contribution of ET-1 and α-adrenergic receptors in the regulation of skeletal muscle blood flow in the human leg at rest and suggest a similar, intensity-dependent “lysis” of peripheral ET and α-adrenergic vasoconstriction during dynamic exercise.

scholarly journals Taming the “sleeping giant”: the role of endothelin-1 in the regulation of skeletal muscle blood flow and arterial blood pressure during exercise

2013 ◽  
Vol 304 (1) ◽  
pp. H162-H169 ◽  
Author(s):  
Zachary Barrett-O'Keefe ◽  
Stephen J. Ives ◽  
Joel D. Trinity ◽  
Garrett Morgan ◽  
Matthew J. Rossman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiovascular Response ◽  
Muscle Blood Flow ◽  
Knee Extensor ◽  
Leg Blood Flow ◽  
Arterial Blood ◽  
Before And After ◽  
Exercise Induced ◽  
Response To Exercise

The cardiovascular response to exercise is governed by a combination of vasodilating and vasoconstricting influences that optimize exercising muscle perfusion while protecting mean arterial pressure (MAP). The degree to which endogenous endothelin (ET)-1, the body's most potent vasoconstrictor, participates in this response is unknown. Thus, in eight young (24 ± 2 yr), healthy volunteers, we examined leg blood flow, MAP, tissue oxygenation, heart rate, leg arterial-venous O2 difference, leg O2 consumption, pH, and net ET-1 and lactate release at rest and during knee extensor exercise (0, 5, 10, 15, 20, and 30 W) before and after an intra-arterial infusion of BQ-123 [ET subtype A (ETA) receptor antagonist]. At rest, BQ-123 did not evoke a change in leg blood flow or MAP. During exercise, net ET-1 release across the exercising leg increased approximately threefold. BQ-123 increased leg blood flow by ∼20% across all work rates (changes of 113 ± 76, 176 ± 83, 304 ± 108, 364 ± 130, 502 ± 117, and 570 ± 178 ml/min at 0, 5, 10, 15, 20, and 30 W, respectively) and attenuated the exercise-induced increase in MAP by ∼6%. The increase in leg blood flow was accompanied by a ∼9% increase in leg O2 consumption with an unchanged arterial-venous O2 difference and deoxyhemoglobin, suggesting a decline in intramuscular efficiency after ETA receptor blockade. Together, these findings identify a significant role of the ET-1 pathway in the cardiovascular response to exercise, implicating vasoconstriction via the ETA receptor as an important mechanism for both the restraint of blood flow in the exercising limb and maintenance of MAP in healthy, young adults.

scholarly journals Exercise-induced hyperemia is associated with knee extensor fatigability in adults with type 2 diabetes

2019 ◽  
Vol 126 (3) ◽  
pp. 658-667 ◽  
Author(s):  
Jonathon W. Senefeld ◽  
Jacqueline K. Limberg ◽  
Kathleen M. Lukaszewicz ◽  
Sandra K. Hunter
Keyword(s):  
Type 2 Diabetes ◽  
Blood Flow ◽  
Lower Limb ◽  
Contractile Function ◽  
Muscle Blood Flow ◽  
Knee Extensor ◽  
Dynamic Exercise ◽  
Extensor Muscles ◽  
Exercise Induced

The aim of this study was to compare fatigability, contractile function, and blood flow to the knee extensor muscles after dynamic exercise in patients with type 2 diabetes mellitus (T2DM) and controls. The hypotheses were that patients with T2DM would demonstrate greater fatigability than controls, and greater fatigability would be associated with a lower exercise-induced increase in blood flow and greater impairments in contractile function. Patients with T2DM ( n = 15; 8 men; 62.4 ± 9.0 yr; 30.4 ± 7.7 kg/m2; 7,144 ± 3,294 steps/day) and 15 healthy control subjects (8 men, 58.4 ± 6.9 yr; 28.4 ± 4.6 kg/m2; 7,893 ± 2,323 steps/day) were matched for age, sex, body mass index, and physical activity. Fatigability was quantified as the reduction in knee extensor power during a 6-min dynamic exercise. Before and after exercise, vascular ultrasonography and electrical stimulation were used to assess skeletal muscle blood flow and contractile properties, respectively. Patients with T2DM had greater fatigability (30.0 ± 20.1% vs. 14.6 ± 19.0%, P < 0.001) and lower exercise-induced hyperemia (177 ± 90% vs. 194 ± 79%, P = 0.04) than controls but similar reductions in the electrically evoked twitch amplitude (37.6 ± 24.8% vs. 31.6 ± 30.1%, P = 0.98). Greater fatigability of the knee extensor muscles was associated with postexercise reductions in twitch amplitude ( r = 0.64, P = 0.001) and lesser exercise-induced hyperemia ( r = −0.56, P = 0.009). Patients with T2DM had greater lower-limb fatigability during dynamic exercise, which was associated with reduced contractile function and lower skeletal muscle blood flow. Thus, treatments focused on enhancing perfusion and reversing impairments in contractile function in patients with T2DM may offset lower-limb fatigability and aid in increasing exercise capacity. NEW & NOTEWORTHY Although prior studies compare patients with type 2 diabetes mellitus (T2DM) with lean controls, our study includes controls matched for age, body mass, and physical activity to more closely assess the effects of T2DM. Patients with T2DM demonstrated no impairment in macrovascular endothelial function, evidenced by similar flow-mediated dilation to controls. However, patients with T2DM had greater fatigability and reduced exercise-induced increase in blood flow (hyperemia) after a lower-limb dynamic fatiguing exercise compared with controls.

scholarly journals Ascorbic acid increases muscle blood flow during dynamic exercise in older healthy humans

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Brett S Kirby ◽  
Wyatt F Voyles ◽  
Carrie B Simpson ◽  
Rick E Carlson ◽  
William G Schrage ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ascorbic Acid ◽  
Muscle Blood Flow ◽  
Dynamic Exercise ◽  
Healthy Humans

Differential effects of aging on limb blood flow in humans

2006 ◽  
Vol 290 (1) ◽  
pp. H272-H278 ◽  
Author(s):  
Anthony J. Donato ◽  
Abhimanyu Uberoi ◽  
D. Walter Wray ◽  
Steven Nishiyama ◽  
Lesley Lawrenson ◽  
...  
Keyword(s):  
Blood Flow ◽  
Muscle Mass ◽  
Knee Extensor ◽  
Quadriceps Muscle ◽  
Vascular Conductance ◽  
Leg Blood Flow ◽  
Arterial Blood ◽  
Relative Exercise Intensity ◽  
Effects Of Aging ◽  
Forearm Muscle

Aging appears to attenuate leg blood flow during exercise; in contrast, such data are scant and do not support this contention in the arm. Therefore, to determine whether aging has differing effects on blood flow in the arm and leg, eight young (22 ± 6 yr) and six old (71 ± 15 yr) subjects separately performed dynamic knee extensor [0, 3, 6, 9 W; 20, 40, 60% maximal work rate (WRmax)] and handgrip exercise (3, 6, 9 kg at 0.5 Hz; 20, 40, 60% WRmax). Arterial diameter, blood velocity (Doppler ultrasound), and arterial blood pressure (radial tonometry) were measured simultaneously at each of the submaximal workloads. Quadriceps muscle mass was smaller in the old (1.6 ± 0.1 kg) than the young (2.1 ± 0.2 kg). When normalized for this difference in muscle mass, resting seated blood flow was similar in young and old subjects (young, 115 ± 28; old, 114 ± 39 ml·kg−1·min−1). During exercise, blood flow and vascular conductance were attenuated in the old whether expressed in absolute terms for a given absolute workload or more appropriately expressed as blood flow per unit muscle mass at a given relative exercise intensity (young, 1,523 ± 329; old, 1,340 ± 157 ml·kg−1·min−1 at 40% WRmax). In contrast, aging did not affect forearm muscle mass or attenuate rest or exercise blood flow or vascular conductance in the arm. In conclusion, aging induces limb-specific alterations in exercise blood flow regulation. These alterations result in reductions in leg blood flow during exercise but do not impact forearm blood flow.

scholarly journals Role of α1-adrenergic vasoconstriction in the regulation of skeletal muscle blood flow with advancing age

2009 ◽  
Vol 296 (2) ◽  
pp. H497-H504 ◽  
Author(s):  
D. Walter Wray ◽  
Steven K. Nishiyama ◽  
Russell S. Richardson
Keyword(s):  
Blood Flow ◽  
Muscle Blood Flow ◽  
Knee Extensor ◽  
The Elderly ◽  
Work Rate ◽  
Leg Blood Flow ◽  
Vasoconstrictor Response ◽  
Leg Exercise ◽  
Exercise Induced ◽  
Induced Changes

α1-Adrenergic vasoconstriction during dynamic leg exercise is diminished in younger individuals, although the extent of this exercise-induced “sympatholysis” in the elderly remains uncertain. Thus, in nine young (25 ± 1 yr) and six older (72 ± 2 yr) healthy volunteers, we evaluated changes in leg blood flow (ultrasound Doppler) during blood flow-adjusted intra-arterial infusion of phenylephrine (PE; a selective α1-adrenergic agonist) at rest and during knee-extensor leg exercise at 20, 40, and 60% of maximal work rate (WRmax). To probe the potential contributors to exercise-induced changes in α1-adrenergic receptor sensitivity, exercising leg O2 consumption (V̇o2) and lactate efflux were also evaluated ( n = 10). At rest, the PE-induced vasoconstriction (i.e., decrease in leg blood flow) was diminished in older (−37 ± 3%) compared with young (−54 ± 4%) subjects. During exercise, the magnitude of α1-adrenergic vasoconstriction in the active leg decreased in both groups. However, compared with young, older subjects maintained a greater vasoconstrictor response to PE at 40% WRmax (−14 ± 3%, older; −7 ± 2%, young) and 60% WRmax (−11 ± 3%, older; −4 ± 3%, young). It is possible that this observation may be attributed to lower absolute work rates in the older group, because, for a similar absolute work rate (≈10 W) and leg V̇o2 (≈0.36 l/min), vasoconstriction to PE was not different between groups (−14 ± 3%; older; −17 ± 5%, young). Together, these data challenge the concept of reduced sympatholysis in the elderly, suggesting instead that the inhibition of α1-adrenergic vasoconstriction in the exercising leg is associated with work performed and, therefore, more closely related to the rate of oxidative metabolism than to age per se.

Effects of Manual Acupuncture with Sparrow Pecking on Muscle Blood Flow of Normal and Denervated Hindlimb in Rats

2008 ◽  
Vol 26 (3) ◽  
pp. 149-159 ◽  
Author(s):  
Hisashi Shinbara ◽  
Masamichi Okubo ◽  
Eiji Sumiya ◽  
Fumihiko Fukuda ◽  
Tadashi Yano ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Muscle Blood Flow ◽  
Dependent Manner ◽  
Manual Acupuncture ◽  
Sprague Dawley ◽  
Axon Reflex ◽  
Hindlimb Muscles ◽  
Arterial Blood ◽  
The Right

Introduction In clinical practice, it has been thought that acupuncture might serve to wash out pain-generating metabolic end-products by improving blood circulation in muscles. We investigated the effects of manual acupuncture (MA) on muscle blood flow (MBF) of normal and denervated hindlimbs in rats. Method Sprague-Dawley rats (n=100) anaesthetised with urethane (1.2g/kg ip) were used. Manual acupuncture with sparrow pecking (SP) at different doses (1, 10 or 30 pecks) was given to the right ventral hindlimb muscles (tibial anterior and extensor digitorum longus muscles) or the right dorsal hindlimb muscles (gastrocnemius, plantaris and soleus muscles). MBF with or without MA was measured using the radiolabelled microsphere technique. The blood pressure was recorded through the right common carotid artery until MBF measurement started. Denervation of hindlimb was conducted by cutting the sciatic and femoral nerves. Results In normal rats, significantly increased MBF after MA were observed only in muscles which were penetrated by an acupuncture needle. The size of the increase depended on the number of times of pecking and seemed to be sustained at least until 60 minutes after MA. However, the increase was observed after both acute and chronic denervation. On the other hand, the mean arterial blood pressure (MAP) did not change significantly before, during or after MA. Conclusion These results suggest that MA could increase muscle blood flow locally in a dose-dependent manner and that this increase may be caused by local vasodilators, as well as the axon reflex. A further study is needed to elucidate the mechanism.

Intensity-dependent thermoregulatory responses at the onset of dynamic exercise in mildly heated humans

2003 ◽  
Vol 285 (1) ◽  
pp. R200-R207 ◽  
Author(s):  
Shuji Yanagimoto ◽  
Tomoko Kuwahara ◽  
Yuan Zhang ◽  
Shunsaku Koga ◽  
Yoshimitsu Inoue ◽  
...  
Keyword(s):  
Blood Flow ◽  
Exercise Intensity ◽  
Perceived Exertion ◽  
Dynamic Exercise ◽  
Rating Of Perceived Exertion ◽  
Cutaneous Blood Flow ◽  
Cycle Exercise ◽  
Arterial Blood ◽  
The Mean ◽  
Cutaneous Blood

To investigate quantitatively how sweating and cutaneous blood flow responses at the onset of dynamic exercise are affected by increasing exercise intensity in mildly heated humans, 18 healthy male subjects performed cycle exercise at 30, 50, and 70% of maximal O2 uptake (V̇O2 max) for 60 s in a warm environment. The study was conducted in a climatic chamber with a regulated ambient temperature of 35°C and relative humidity of 50%. The subjects rested in the semisupine position in the chamber for 60 min, and then sweating rate (SR) and skin blood flow were measured during cycle exercise at three different intensities. Changes in the heart rate, rating of perceived exertion, and mean arterial blood pressure were proportional to increasing exercise intensity, whereas esophageal and mean skin temperatures were essentially constant throughout the experiment. The SR on the chest, forearm, and thigh, but not on the palm, increased significantly with increasing exercise intensity ( P < 0.05). The mean SR of the chest, forearm, and thigh increased 0.05 mg·cm-2·min-1 with an increase in exercise intensity equivalent to 10% V̇O2 max. On the other hand, the cutaneous vascular conductance (CVC) on the chest, forearm, and palm decreased significantly with increasing exercise intensity ( P < 0.05). The mean CVC of the chest and forearm decreased 5.5% and the CVC on the palm decreased 8.0% with an increase in exercise intensity equivalent to 10% V̇O2 max. In addition, the reduction in CVC was greater on the palm than on the chest and forearm at all exercise intensities ( P < 0.01). We conclude that nonthermal sweating and cutaneous blood flow responses are exercise intensity dependent but directionally opposite at the onset of dynamic exercise in mildly heated humans. Furthermore, cutaneous blood flow responses to increased exercise intensity are greater in glabrous (palm) than in nonglabrous (chest and forearm) skin.

scholarly journals Respiratory muscle work compromises leg blood flow during maximal exercise

1997 ◽  
Vol 82 (5) ◽  
pp. 1573-1583 ◽  
Author(s):  
Craig A. Harms ◽  
Mark A. Babcock ◽  
Steven R. McClaran ◽  
David F. Pegelow ◽  
Glenn A. Nickele ◽  
...  
Keyword(s):  
Blood Flow ◽  
Respiratory Muscle ◽  
Maximal Exercise ◽  
Minute Ventilation ◽  
Muscle Blood Flow ◽  
Work Of Breathing ◽  
Esophageal Pressure ◽  
Leg Blood Flow ◽  
Muscle Work ◽  
Arterial Blood

Harms, Craig A., Mark A. Babcock, Steven R. McClaran, David F. Pegelow, Glenn A. Nickele, William B. Nelson, and Jerome A. Dempsey.Respiratory muscle work compromises leg blood flow during maximal exercise. J. Appl. Physiol.82(5): 1573–1583, 1997.—We hypothesized that during exercise at maximal O2 consumption (V˙o 2 max), high demand for respiratory muscle blood flow (Q˙) would elicit locomotor muscle vasoconstriction and compromise limb Q˙. Seven male cyclists (V˙o 2 max 64 ± 6 ml ⋅ kg−1 ⋅ min−1) each completed 14 exercise bouts of 2.5-min duration atV˙o 2 max on a cycle ergometer during two testing sessions. Inspiratory muscle work was either 1) reduced via a proportional-assist ventilator, 2) increased via graded resistive loads, or 3) was not manipulated (control). Arterial (brachial) and venous (femoral) blood samples, arterial blood pressure, leg Q˙ (Q˙legs; thermodilution), esophageal pressure, and O2 consumption (V˙o 2) were measured. Within each subject and across all subjects, at constant maximal work rate, significant correlations existed ( r = 0.74–0.90; P < 0.05) between work of breathing (Wb) and Q˙legs (inverse), leg vascular resistance (LVR), and leg V˙o 2(V˙o 2 legs; inverse), and between LVR and norepinephrine spillover. Mean arterial pressure did not change with changes in Wb nor did tidal volume or minute ventilation. For a ±50% change from control in Wb,Q˙legs changed 2 l/min or 11% of control, LVR changed 13% of control, and O2extraction did not change; thusV˙o 2 legschanged 0.4 l/min or 10% of control. TotalV˙o 2 max was unchanged with loading but fell 9.3% with unloading; thusV˙o 2 legsas a percentage of totalV˙o 2 max was 81% in control, increased to 89% with respiratory muscle unloading, and decreased to 71% with respiratory muscle loading. We conclude that Wb normally incurred during maximal exercise causes vasoconstriction in locomotor muscles and compromises locomotor muscle perfusion andV˙o 2.

Distribution of blood flow in muscles of miniature swine during exercise

1987 ◽  
Vol 62 (3) ◽  
pp. 1285-1298 ◽  
Author(s):  
R. B. Armstrong ◽  
M. D. Delp ◽  
E. F. Goljan ◽  
M. H. Laughlin
Keyword(s):  
Blood Flow ◽  
Exercise Intensity ◽  
Skeletal Muscles ◽  
Muscle Blood Flow ◽  
Peak Exercise ◽  
Fiber Types ◽  
Miniature Swine ◽  
Blood Flows ◽  
Limb Muscles ◽  
Total Muscle

The purpose of this study was to determine how the distribution of blood flow within and among the skeletal muscles of miniature swine (22 +/- 1 kg body wt) varies as a function of treadmill speed. Radiolabeled microspheres were used to measure cardiac output (Q) and tissue blood flows in preexercise and at 3–5 min of treadmill exercise at 4.8, 8.0, 11.3, 14.5, and 17.7 km/h. All pigs (n = 8) attained maximal O2 consumption (VO2max) (60 +/- 4 ml X min-1 X kg-1) by the time they ran at 17.7 km/h. At VO2max, 87% of Q (9.9 +/- 0.5 l/min) was to skeletal muscle, which constituted 36 +/- 1% of body mass. Average total muscle blood flow at VO2max was 127 +/- 14 ml X min-1 X 100 g-1; average limb muscle flow was 135 +/- 17 ml X min-1 X 100 g-1. Within the limb muscles, blood flow was distributed so that the deep red parts of extensor muscles had flows about two times higher than the more superficial white portions of the same muscles; the highest muscle blood flows occurred in the elbow flexors (brachialis: 290 +/- 44 ml X min-1 X 100 g-1). Peak exercise blood flows in the limb muscles were proportional (P less than 0.05) to the succinate dehydrogenase activities (r = 0.84), capillary densities (r = 0.78), and populations of oxidative (slow-twitch oxidative + fast-twitch oxidative-glycolytic) fiber types (r = 0.93) in the muscles. Total muscle blood flow plotted as a function of exercise intensity did not peak until the pigs attained VO2max, although flows in some individual muscles showed a plateau in this relationship at submaximal exercise intensities. The data demonstrate that blood flow in skeletal muscles of miniature swine is distributed heterogeneously and varies in relation to fiber type composition and exercise intensity.

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