scholarly journals Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli

2017 ◽  
Vol 97 (2) ◽  
pp. 495-528 ◽  
Author(s):  
Daniel J. Green ◽  
Maria T. E. Hopman ◽  
Jaume Padilla ◽  
M. Harold Laughlin ◽  
Dick H. J. Thijssen
Keyword(s):  
Blood Flow ◽  
Exercise Training ◽  
Vascular Function ◽  
Wall Stress ◽  
Adaptive Responses ◽  
Late 20Th Century ◽  
Hemodynamic Forces ◽  
Response To Exercise ◽  
The Impact

On the 400th anniversary of Harvey's Lumleian lectures, this review focuses on “hemodynamic” forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20th century discovery that endothelial cells modify arterial tone via paracrine transduction provoked studies exploring the direct mechanical effects of blood flow and pressure on vascular function and adaptation in vivo. In this review, we address the impact of distinct hemodynamic signals that occur in response to exercise, the interrelationships between these signals, the nature of the adaptive responses that manifest under different physiological conditions, and the implications for human health. Exercise modifies blood flow, luminal shear stress, arterial pressure, and tangential wall stress, all of which can transduce changes in arterial function, diameter, and wall thickness. There are important clinical implications of the adaptation that occurs as a consequence of repeated hemodynamic stimulation associated with exercise training in humans, including impacts on atherosclerotic risk in conduit arteries, the control of blood pressure in resistance vessels, oxygen delivery and diffusion, and microvascular health. Exercise training studies have demonstrated that direct hemodynamic impacts on the health of the artery wall contribute to the well-established decrease in cardiovascular risk attributed to physical activity.

scholarly journals Effects of aging and exercise training on spinotrapezius muscle microvascular Po2 dynamics and vasomotor control

2011 ◽  
Vol 110 (3) ◽  
pp. 695-704 ◽  
Author(s):  
Danielle J. McCullough ◽  
Robert T. Davis ◽  
James M. Dominguez ◽  
John N. Stabley ◽  
Christian S. Bruells ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Training ◽  
Sodium Nitroprusside ◽  
Vascular Function ◽  
Treadmill Running ◽  
Aged Rats ◽  
Phosphorescence Quenching

With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O2 delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O2 delivery to O2 uptake, evidenced through improved microvascular Po2 (PmO2), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ∼6 mo) and aged (O, >24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n = 16, and OSED; n = 15) or exercise-trained (YET; n = 14, and OET; n = 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify PmO2 in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline PmO2 (OET 37.5 ± 3.9 vs. OSED 24.7 ± 3.6 Torr, P < 0.05); the end-contracting PmO2 and the time-delay before PmO2 fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 ± 16 vs. OSED 27 ± 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the PmO2 in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle.

Blood vessel remodeling and physical inactivity in humans

2011 ◽  
Vol 111 (6) ◽  
pp. 1836-1845 ◽  
Author(s):  
Dick H. J. Thijssen ◽  
Daniel J. Green ◽  
Maria T. E. Hopman
Keyword(s):  
Vascular Function ◽  
Physical Inactivity ◽  
Future Research ◽  
Vessel Remodeling ◽  
Resistance Vessels ◽  
Future Research Directions ◽  
Response To Exercise ◽  
The Impact

Physical inactivity is associated with an increase in cardiovascular risk that cannot be fully explained by traditional or novel risk factors. Inactivity is also associated with changes in hemodynamic stimuli, which exert direct effects on the vasculature leading to remodeling and a proatherogenic phenotype. In this review, we synthesize and summarize in vivo evidence relating to the impact of local and systemic models of physical inactivity on conduit arteries, resistance vessels, and the microcirculation in humans. Taken together, the literature suggests that a rapid inward structural remodeling of vessels occurs in response to physical inactivity. The magnitude of this response is dependent on the “dose” of inactivity. Moreover, changes in vascular function are found at resistance and microvessel levels in humans. In conduit arteries, a strong interaction between vascular function and structure is present, which results in conflicting data regarding the impact of inactivity on conduit artery function. While much of the cardioprotective effect of exercise is related to the nitric oxide pathway, deconditioning may primarily be associated with activation of vasoconstrictor pathways. The effects of deconditioning on the vasculature are therefore not simply the opposite of those in response to exercise training. Given the importance of sedentary behavior, future studies should provide further insight into the impact of inactivity on the vasculature and other (novel) markers of vascular health. Moreover, studies should examine the role of (hemodynamic) stimuli that underlie the characteristic vascular adaptations during deconditioning. Our review concludes with some suggestions for future research directions.

scholarly journals Differential effects of aging and exercise on intra-abdominal adipose arteriolar function and blood flow regulation

2013 ◽  
Vol 114 (6) ◽  
pp. 808-815 ◽  
Author(s):  
Robert T. Davis ◽  
John N. Stabley ◽  
James M. Dominguez ◽  
Michael W. Ramsey ◽  
Danielle J. McCullough ◽  
...  
Keyword(s):  
Blood Flow ◽  
Exercise Training ◽  
Old Age ◽  
Vascular Resistance ◽  
Vascular Function ◽  
Age Groups ◽  
Resistance Arteries ◽  
Age Related

Adipose tissue (AT), which typically comprises an increased percentage of body mass with advancing age, receives a large proportion of resting cardiac output. During exercise, an old age-associated inability to increase vascular resistance within the intra-abdominal AT may compromise the ability of the cardiovascular system to redistribute blood flow to the active musculature, contributing to the decline in exercise capacity observed in this population. We tested the hypotheses that 1) there would be an elevated perfusion of AT during exercise with old age that was associated with diminished vasoconstrictor responses of adipose-resistance arteries, and 2) chronic exercise training would mitigate the age-associated alterations in AT blood flow and vascular function. Young (6 mo; n = 40) and old (24 mo; n = 28) male Fischer 344 rats were divided into young sedentary (YSed), old sedentary (OSed), young exercise trained (YET), or old exercise trained (OET) groups, where training consisted of 10-12 wk of treadmill exercise. In vivo blood flow at rest and during exercise and in vitro α-adrenergic and myogenic vasoconstrictor responses in resistance arteries from AT were measured in all groups. In response to exercise, there was a directionally opposite change in AT blood flow in the OSed group (∼150% increase) and YSed (∼55% decrease) vs. resting values. Both α-adrenergic and myogenic vasoconstriction were diminished in OSed vs. YSed AT-resistance arteries. Exercise training resulted in a similar AT hyperemic response between age groups during exercise (YET, 9.9 ± 0.5 ml·min−1·100−1 g; OET, 8.1 ± 0.9 ml·min−1·100−1 g) and was associated with enhanced myogenic and α-adrenergic vasoconstriction of AT-resistance arteries from the OET group relative to OSed. These results indicate that there is an inability to increase vascular resistance in AT during exercise with old age, due, in part, to a diminished vasoconstriction of AT arteries. Furthermore, the results indicate that exercise training can augment vasoconstriction of AT arteries and mitigate age-related alterations in the regulation of AT blood flow during exercise.

S-nitroso-albumin carries a thiol-labile pool of nitric oxide, which causes venodilation in the rat

2005 ◽  
Vol 289 (2) ◽  
pp. H916-H923 ◽  
Author(s):  
Nelson N. Orie ◽  
Patrick Vallance ◽  
Dean P. Jones ◽  
Kevin P. Moore
Keyword(s):  
Nitric Oxide ◽  
Molecular Weight ◽  
Blood Flow ◽  
Vascular Function ◽  
Low Molecular Weight ◽  
Aortic Blood Flow ◽  
Hemodynamic Effects ◽  
Rapid Decomposition ◽  
Aortic Blood

It is now established that S-nitroso-albumin (SNO-albumin) circulates at low nanomolar concentrations under physiological conditions, but concentrations may increase to micromolar levels during disease states (e.g., cirrhosis or endotoxemia). This study tested the hypothesis that high concentrations of SNO-albumin observed in some diseases modulate vascular function and that it acts as a stable reservoir of nitric oxide (NO), releasing this molecule when the concentrations of low-molecular-weight thiols are increased. SNO-albumin was infused into rats to increase the plasma concentration from <50 nmol/l to ∼4 μmol/l. This caused a 29 ± 6% drop in blood pressure, 20 ± 4% decrease in aortic blood flow, and a 25 ± 14% reduction of renal blood flow within 10 min. These observations were in striking contrast to those of an infused arterial vasodilator (hydralazine), which increased aortic blood flow, and suggested that SNO-albumin acts primarily as a venodilator in vivo. This was confirmed by the observations that glyceryl trinitrate (a venodilator) led to similar hemodynamic changes and that the hemodynamic effects of SNO-albumin are reversed by infusion of colloid. Infusion of N-acetylcysteine into animals with artificially elevated plasma SNO-albumin concentrations led to the rapid decomposition of SNO-albumin in vivo and reproduced the hemodynamic effects of SNO-albumin infusion. These data demonstrate that SNO-albumin acts primarily as a venodilator in vivo and represents a stable reservoir of NO that can release NO when the concentrations of low-molecular-weight thiols are elevated.

scholarly journals METTL3-dependent N6-methyladenosine RNA modification mediates the atherogenic inflammatory cascades in vascular endothelium

2021 ◽  
Vol 118 (7) ◽  
pp. e2025070118
Author(s):  
Chian-Shiu Chien ◽  
Julie Yi-Shuan Li ◽  
Yueh Chien ◽  
Mong-Lien Wang ◽  
Aliaksandr A. Yarmishyn ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Activation ◽  
Plaque Formation ◽  
Rna Modification ◽  
Branch Points ◽  
Monocyte Adhesion ◽  
Down Regulation ◽  
Hemodynamic Forces

Atherosclerosis is characterized by the plaque formation that restricts intraarterial blood flow. The disturbed blood flow with the associated oscillatory stress (OS) at the arterial curvatures and branch points can trigger endothelial activation and is one of the risk factors of atherosclerosis. Many studies reported the mechanotransduction related to OS and atherogenesis; however, the transcriptional and posttranscriptional regulatory mechanisms of atherosclerosis remain unclear. Herein, we investigated the role of N6-methyladenosine (m6A) RNA methylation in mechanotransduction in endothelial cells (ECs) because of its important role in epitranscriptome regulation. We have identified m6A methyltransferase METTL3 as a responsive hub to hemodynamic forces and atherogenic stimuli in ECs. OS led to an up-regulation of METTL3 expression, accompanied by m6A RNA hypermethylation, increased NF-κB p65 Ser536 phosphorylation, and enhanced monocyte adhesion. Knockdown of METTL3 abrogated this OS-induced m6A RNA hypermethylation and other manifestations, while METTL3 overexpression led to changes resembling the OS effects. RNA-sequencing and m6A-enhanced cross-linking and immunoprecipitation (eCLIP) experiments revealed NLRP1 and KLF4 as two hemodynamics-related downstream targets of METTL3-mediated hypermethylation. The METTL3-mediated RNA hypermethylation up-regulated NLRP1 transcript and down-regulated KLF4 transcript through YTHDF1 and YTHDF2 m6A reader proteins, respectively. In the in vivo atherosclerosis model, partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NLRP3 up-regulation, and KLF4 down-regulation. Collectively, we have demonstrated that METTL3 serves a central role in the atherogenesis induced by OS and disturbed blood flow.

scholarly journals Electro-Metabolic Sensing Through Capillary ATP-Sensitive K+ Channels and Adenosine to Control Cerebral Blood Flow

2021 ◽  
Author(s):  
Maria Sancho ◽  
Nicholas R. Klug ◽  
Amreen Mughal ◽  
Thomas J. Heppner ◽  
David Hill-Eubanks ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Vascular Function ◽  
Brain Activity ◽  
List Type ◽  
Capillary Endothelial Cells ◽  
Metabolic Sensing ◽  
Cellular Components

SUMMARYThe dense network of capillaries composed of capillary endothelial cells (cECs) and pericytes lies in close proximity to all neurons, ideally positioning it to sense neuro/glial-derived compounds that regulate regional and global cerebral perfusion. The membrane potential (VM) of vascular cells serves as the essential output in this scenario, linking brain activity to vascular function. The ATP-sensitive K+ channel (KATP) is a key regulator of vascular VM in other beds, but whether brain capillaries possess functional KATP channels remains unknown. Here, we demonstrate that brain capillary ECs and pericytes express KATP channels that robustly control VM. We further show that the endogenous mediator adenosine acts through A2A receptors and the Gs/cAMP/PKA pathway to activate capillary KATP channels. Moreover, KATP channel stimulation in vivo causes vasodilation and increases cerebral blood flow (CBF). These findings establish the presence of KATP channels in cECs and pericytes and suggest their significant influence on CBF.HIGHLIGHTSCapillary network cellular components—endothelial cells and pericytes—possess functional KATP channels.Activation of KATP channels causes profound hyperpolarization of capillary cell membranes.Capillary KATP channels are activated by exogenous adenosine via A2A receptors and cAMP-dependent protein kinase.KATP channel activation by adenosine or synthetic openers increases cerebral blood flow.

Abstract 14820: Sirt7 Deficiency in Blood Vessel Components Impairs Vascular Function by Inhibiting Cell Cycle- and Inflammatory-Related Protein Expression

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yuichi Kimura ◽  
Yasuhiro Izumiya ◽  
Satoshi Araki ◽  
Satoru Yamamura ◽  
Yoshiro Onoue ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Vascular Diseases ◽  
Tube Formation ◽  
Hindlimb Ischemia ◽  
Proliferation Assay

Introduction: Aging is a well-established cardiovascular risk factor and associated with vascular dysfunction. Sirt7, one of the members of mammalian sirtuin family, is thought to be involved in age-related diseases. However, little is known about the relative contribution of Sirt7 in vascular dysfunction. Hypothesis: Sirt7 maintains vascular cell functions and its deficiency plays a critical role in vascular diseases. Methods: Sirt7 loss- and gain-of-function experiments were performed with human aortic smooth muscle cells (HAoSMCs) and human umbilical vein endothelial cells (HUVECs). In vivo, blood flow recovery was evaluated by hindlimb ischemia model in homozygous Sirt7 deficient (Sirt7-/-) and wild-type (WT) mice. Irradiated WT mice were intravenously received bone marrow (BM) cells from WT or Sirt7 -/- mouse to achieve BM transfer. Results: An RNAi-medicated Sirt7 knockdown resulted in a significant inhibition of HAoSMCs proliferation following serum or Platelet-derived growth factor BB (PDGF-BB) stimulation as determined by cell count, BrdU cell proliferation assay and MTS proliferation assay. Knockdown of endogenous Sirt7 also reduced cell migration as revealed by Boyden chamber migration assay. The Cyclin D1 and Cyclin dependent kinase 2 (CDK2) protein levels were significantly decreased in Sirt7 siRNA-treated HAoSMCs in response to serum or PDGF-BB stimulation. In endothelial cells, knockdown of Sirt7 attenuated tube formation, proliferation and migration. These changes were accompanied by reduced ERK activation and VCAM-1 mRNA and protein expression in Sirt7 siRNA-treated HUVECs. Conversely, overexpression of Sirt7 by adenovirus enhanced tube formation and cell proliferation. In vivo, blood flow recovery in response to hindlimb ischemia was significantly attenuated in Sirt7-/- mice compared with WT mice. There was no difference in blood flow recovery between WT mice transplanted with WT or Sirt7-/- BM cells suggesting that Sirt7 deficiency in vascular cells have a predominant effect on attenuated blood flow recovery in response to hindlimb ischemia. Conclusions: Sirt7 in blood vessel components have an important role in maintenance of vascular function. Sirt7 could be a promising therapeutic target for vascular diseases.

The passive leg movement technique for assessing vascular function: the impact of baseline blood flow

2021 ◽  
Vol 106 (10) ◽  
pp. 2133-2147
Author(s):  
Katherine L. Shields ◽  
Ryan M. Broxterman ◽  
Catherine L. Jarrett ◽  
Angela V. Bisconti ◽  
Soung Hun Park ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Function ◽  
Leg Movement ◽  
The Impact

scholarly journals The passive leg movement technique for assessing vascular function: defining the distribution of blood flow and the impact of occluding the lower leg

2019 ◽  
Vol 104 (10) ◽  
pp. 1575-1584 ◽  
Author(s):  
Katherine L. Shields ◽  
Ryan M. Broxterman ◽  
Catherine L. Jarrett ◽  
Angela V. Bisconti ◽  
Soung Hun Park ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Function ◽  
Lower Leg ◽  
Leg Movement ◽  
The Impact

Effects of exercise on endothelium and endothelium/smooth muscle cross talk: role of exercise-induced hemodynamics

2011 ◽  
Vol 111 (1) ◽  
pp. 311-320 ◽  
Author(s):  
S. C. Newcomer ◽  
Dick H. J. Thijssen ◽  
D. J. Green
Keyword(s):  
Physical Activity ◽  
Shear Stress ◽  
Wall Stress ◽  
Beneficial Effects ◽  
Exercise Induced ◽  
Response To Exercise ◽  
And Training

Physical activity, exercise training, and fitness are associated with decreased cardiovascular risk. In the context that a risk factor “gap” exists in the explanation for the beneficial effects of exercise on cardiovascular disease, it has recently been proposed that exercise generates hemodynamic stimuli which exert direct effects on the vasculature that are antiatherogenic. In this review we briefly introduce some of the in vitro and in vivo evidence relating exercise hemodynamic modulation and vascular adaptation. In vitro data clearly demonstrate the importance of shear stress as a potential mechanism underlying vascular adaptations associated with exercise. Supporting this is in vivo human data demonstrating that exercise-mediated shear stress induces localized impacts on arterial function and diameter. Emerging evidence suggests that exercise-related changes in hemodynamic stimuli other than shear stress may also be associated with arterial remodeling. Taken together, in vitro and in vivo data strongly imply that hemodynamic influences combine to orchestrate a response to exercise and training that regulates wall stress and peripheral vascular resistance and contributes to the antiatherogenic impacts of physical activity, fitness, and training.

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