Shear level influences resistance artery remodeling: wall dimensions, cell density, and eNOS expression

Tuttle, Jay; Nachreiner, Ryan; Bhuller, Amardip S.; Condict, Kevin W.; Connors, Bret A.; Herring, B. Paul; Dalsing, Michael C.; Unthank, Joseph L.

doi:10.1152/ajpheart.2001.281.3.h1380

Cited by 214 publications

(227 citation statements)

References 57 publications

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“…30 Similar observations were made by our group and others. 27,30,41,42 In the present study, we observed flowinduced outward hypertrophic remodeling but no hypotrophy in resistance arteries exposed to low blood flow in normotensive Wistar rats studied between 10 and 14 weeks of age. This indicates dependence of flow-related arterial remodeling on rat age 43 and strain.…”

Section: Discussionsupporting

confidence: 56%

Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

et al. 2012

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Arteries from young healthy animals respond to chronic changes in blood flow and blood pressure by structural remodeling. We tested whether the ability to respond to decreased ( À90%) or increased ( þ 100%) blood flow is impaired during the development of deoxycorticosterone acetate (DOCA)-salt hypertension in rats, a model for an upregulated endothelin-1 system. Mesenteric small arteries (MrA) were exposed to low blood flow (LF) or high blood flow (HF) for 4 or 7 weeks. The bioavailability of vasoactive peptides was modified by chronic treatment of the rats with the dual neutral endopeptidase (NEP)/endothelin-converting enzyme (ECE) inhibitor SOL1. After 3 or 6 weeks of hypertension, the MrA showed hypertrophic arterial remodeling (3 weeks: media cross-sectional area (mCSA): 10 ± 1 Â 10 3 to 17 ± 2 Â 10 3 lm 2 ; 6 weeks: 13 ± 2 Â 10 3 to 24 ± 3 Â 10 3 lm 2 ). After 3, but not 6, weeks of hypertension, the arterial diameter was increased (Ø: 385 ± 13 to 463±14 lm). SOL1 reduced hypertrophy after 3 weeks of hypertension (mCSA: 6 Â 10 3 ±1 Â 10 3 lm 2 ). The diameter of the HF arteries of normotensive rats increased (Ø: 463 ± 22 lm) but no expansion occurred in the HF arteries of hypertensive rats (Ø: 471 ± 16 lm). MrA from SOL1-treated hypertensive rats did show a significant diameter increase (Ø: 419 ± 13 to 475±16 lm). Arteries exposed to LF showed inward remodeling in normotensive and hypertensive rats (mean Ø between 235 and 290 lm), and infiltration of monocyte/macrophages. SOL1 treatment did not affect the arterial diameter of LF arteries but reduced the infiltration of monocyte/macrophages. We show for the first time that flow-induced remodeling is impaired during the development of DOCA-salt hypertension and that this can be prevented by chronic NEP/ECE inhibition.

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Section: Discussionsupporting

confidence: 56%

Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

et al. 2012

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“…22,23 Subsequent animal studies consolidated the link between increases in flow, wall shear stress, endothelial NO synthase expression, and NO bioactivity. 24,25 Together, this evidence strongly suggests that flow and shear are physiological stimuli that induce NO production from the endothelium in vivo. However, it is important to note that other vasoactive substances can also be released by the endothelium in response to shear stress (eg, prostacyclin and endothelial derived hyperpolarizing factor).…”

Section: Physiological Basis For the Prognostic Value Of Fmdmentioning

confidence: 86%

Flow-Mediated Dilation and Cardiovascular Event Prediction

et al. 2011

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Abstract-Endothelial dysfunction is an early atherosclerotic event that precedes clinical symptoms and may also render established plaque vulnerable to rupture. Noninvasive assessment of endothelial function is commonly undertaken using the flow-mediated dilation (FMD) technique. Some studies indicate that FMD possesses independent prognostic value to predict future cardiovascular events that may exceed that associated with traditional risk factor assessment. It has been assumed that this association is related to the proposal that FMD provides an index of endothelium-derived nitric oxide (NO) function. Interestingly, placement of the occlusion cuff during the FMD procedure alters the shear stress stimulus and NO dependency of the resulting dilation: cuff placement distal to the imaged artery leads to a largely NO-mediated response, whereas proximal cuff placement leads to dilation which is less NO dependent. We used this physiological observation and the knowledge that prognostic studies have used both approaches to examine whether the prognostic capacity of FMD is related to its role as a putative index of NO function. In a meta-analysis of 14 studies (Ͼ8300 subjects), we found that FMD derived using a proximal cuff was at least as predictive as that derived using distal cuff placement, despite the latter being more NO dependent. This suggests that, whilst FMD is strongly predictive of future cardiovascular events, this may not solely be related to its assumed NO dependency. Although this finding should be confirmed with more and larger studies, we suggest that any direct measure of vascular (endothelial) function may provide independent prognostic information in humans. Cost-effective prevention of cardiovascular disease (CVD) is predicated on cardiovascular risk assessment, which aims to distinguish between individuals at high and low risk of future disease manifestation. An optimal screening method should be inexpensive, relatively noninvasive and reproducible. It should predict risk in patients with known disease and, ideally, the future risk of events in currently healthy asymptomatic populations. 1 Despite several decades of development and refinement, algorithms for the prediction of cardiovascular risk in humans that are based on "traditional" or "conventional" risk factors fail to predict a substantial proportion of cardiovascular events. 1 A recent review pertaining to identification of the "vulnerable patient" concluded that high Framingham risk scores fall short in accurately predicting events in individual patients and cannot provide a clear clinical route for identification or treatment of near future victims of acute coronary syndrome or sudden death. 1 A recent computed tomography angiographic study of 1650 subjects concluded that only 55% of patients with a high plaque burden had high National Cholesterol Education Program/Framingham risk scores. Of the patients identified as high risk by Framingham in this study, 10% had no evidence of plaque, 32% with no plaque were taking statins based on t...

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“…Because it is well known that shear stress is a potent physiologic stimulus for NO release, the increased levels of basal shear stress may lead to an upregulation of endothelial nitric oxide synthase (eNOS). A recent training study in patients with coronary artery disease 33 and previous in vivo 34 and cell culture studies 2,35 have shown that increases in shear stress levels are associated with an elevation of eNOS messenger ribonucleic acid protein and NOS activity. A second possible explanation may be the lack of periods of high shear stress in the vessels supplying the paralyzed and inactive leg muscles of people with SCI, which may contribute to an upregulation of NO responsiveness.…”

Section: Endothelial Functionmentioning

confidence: 97%

Rapid and Extensive Arterial Adaptations After Spinal Cord Injury

Groot¹,

Bleeker²,

Kuppevelt³

et al. 2006

Archives of Physical Medicine and Rehabilitation

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Objective: To assess the time course of adaptations in leg vascular dimension and function within the first 6 weeks after a spinal cord injury (SCI).Design: Longitudinal study design. Setting: University medical center and rehabilitation clinic. Participants: Six men were studied serially at 1, 2, 3, 4, and 6 weeks after SCI.Interventions: Not applicable. Main Outcome Measures: Diameter, blood flow, and shear rate levels of the common femoral artery (CFA), superficial femoral artery (SFA), brachial artery, and carotid artery were measured with echo Doppler ultrasound (diameter, blood flow, shear rate). Endothelial function in the SFA was measured with flow-mediated dilation (FMD). In addition, leg volume and blood pressure measurements were performed.Results: Femoral artery diameter (CFA, 25%; SFA, 16%; PϽ.01) and leg volume (22%, PϽ.01) decreased simultaneously, and these reductions were largely accomplished within 3 weeks postinjury. Significant increases were observed for basal shear rate levels (64% increase at week 3; 117% increase at week 6; PϽ.01), absolute FMD responses (8% increase at week 3, 23% increase at week 6; PϽ.05) and relative FMD responses (26% increase at week 3, 44% increase at week 6; PϽ.001).Conclusions: Our findings show a rapid onset of adaptations in arterial dimension and function to extreme inactivity in humans. Vascular adaptations include extensive reductions in femoral diameter and leg volume, as well as increased basal shear rate levels and FMD responses, which all appear to be largely accomplished within 3 weeks after an SCI.

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Shear level influences resistance artery remodeling: wall dimensions, cell density, and eNOS expression

Cited by 214 publications

References 57 publications

Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

Flow-Mediated Dilation and Cardiovascular Event Prediction

Rapid and Extensive Arterial Adaptations After Spinal Cord Injury

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