Endothelial NOS is main mediator for shear stress-dependent angiogenesis in skeletal muscle after prazosin administration

2004 ◽  
Vol 287 (5) ◽  
pp. H2300-H2308 ◽  
Author(s):  
Oliver Baum ◽  
Luis Da Silva-Azevedo ◽  
Gregor Willerding ◽  
Achim Wöckel ◽  
Gerit Planitzer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Knockout Mice ◽  
Skeletal Muscles ◽  
Capillary Density ◽  
Enos Expression ◽  
Wall Shear ◽  
Stress Dependent ◽  
Endothelial Nitric Oxide

The increase of wall shear stress in capillaries by oral administration of the α1-adrenergic receptor antagonist prazosin induces angiogenesis in skeletal muscles. Because endothelial nitric oxide synthase (eNOS) is upregulated in response to elevated wall shear stress, we investigated the relevance of eNOS for prazosin-induced angiogenesis in skeletal muscles. Prazosin and/or the NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) were given to C57BL/6 wild-type mice and eNOS-knockout mice for 14 days. The capillary-to-fiber (C/F) ratio and capillary density (CD; no. of capillaries/mm2) were determined in frozen sections from extensor digitorum longus (EDL) muscles of these mice. Immunoblotting was performed to quantify eNOS expression in endothelial cells isolated from skeletal muscles, whereas VEGF (after precipitation with heparin-agarose) and neuronal NOS (nNOS) concentrations were determined in EDL solubilizates. In EDL muscles of C57BL/6 mice treated for 14 days, the C/F ratio was 28% higher after prazosin administration and 11% higher after prazosin and l-NAME feeding, whereas the CD increased by 21 and 13%, respectively. The C/F ratio was highest after day 4 of prazosin treatment and decreased gradually to almost constant values after day 8. Prazosin administration led to elevation of eNOS expression. VEGF levels were lowest at day 4, whereas nNOS values decreased after day 8. In EDL muscles of eNOS-knockout mice, no significant changes in C/F ratio, CD, or VEGF and nNOS expression were observed in response to prazosin administration. Our data suggest that the presence of eNOS is essential for prazosin-induced angiogenesis in skeletal muscle, albeit other signaling molecules might partially compensate for or contribute to this angiogenic activity. Furthermore, subsequent remodeling of the capillary system accompanied by sequential downregulation of VEGF and nNOS in skeletal muscle fibers characterizes shear stress-dependent angiogenesis.

scholarly journals Branching exponent heterogeneity and wall shear stress distribution in vascular trees

2001 ◽  
Vol 280 (3) ◽  
pp. H1256-H1263 ◽  
Author(s):  
Kelly L. Karau ◽  
Gary S. Krenz ◽  
Christopher A. Dawson
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Coefficient Of Variation ◽  
Vessel Diameter ◽  
Mean Value ◽  
Heterogeneous Distribution ◽  
Uniform Shear ◽  
The Mean ◽  
Wall Shear ◽  
Stress Dependent

A bifurcating arterial system with Poiseuille flow can function at minimum cost and with uniform wall shear stress if the branching exponent ( z) = 3 [where z is defined by ( D 1) z = ( D 2) z + ( D 3) z ; D 1 is the parent vessel diameter and D 2 and D 3 are the two daughter vessel diameters at a bifurcation]. Because wall shear stress is a physiologically transducible force, shear stress-dependent control over vessel diameter would appear to provide a means for preserving this optimal structure through maintenance of uniform shear stress. A mean z of 3 has been considered confirmation of such a control mechanism. The objective of the present study was to evaluate the consequences of a heterogeneous distribution of z values about the mean with regard to this uniform shear stress hypothesis. Simulations were carried out on model structures otherwise conforming to the criteria consistent with uniform shear stress when z = 3 but with varying distributions of z. The result was that when there was significant heterogeneity in z approaching that found in a real arterial tree, the coefficient of variation in shear stress was comparable to the coefficient of variation in z and nearly independent of the mean value of z. A systematic increase in mean shear stress with decreasing vessel diameter was one component of the variation in shear stress even when the mean z = 3. The conclusion is that the influence of shear stress in determining vessel diameters is not, per se, manifested in a mean value of z. In a vascular tree having a heterogeneous distribution in zvalues, a particular mean value of z (e.g., z = 3) apparently has little bearing on the uniform shear stress hypothesis.

Plasma viscosity regulates capillary perfusion during extreme hemodilution in hamster skinfold model

1998 ◽  
Vol 275 (6) ◽  
pp. H2170-H2180 ◽  
Author(s):  
Amy G. Tsai ◽  
Barbara Friesenecker ◽  
Michael McCarthy ◽  
Hiromi Sakai ◽  
Marcos Intaglietta
Keyword(s):  
Molecular Weight ◽  
Shear Stress ◽  
Capillary Density ◽  
High Viscosity ◽  
Plasma Viscosity ◽  
Capillary Perfusion ◽  
Low Viscosity ◽  
Arterial Blood ◽  
Wall Shear ◽  
Stress Dependent

Effect of increasing blood viscosity during extreme hemodilution on capillary perfusion and tissue oxygenation was investigated in the awake hamster skinfold model. Two isovolemic hemodilution steps were performed with 6% Dextran 70 [molecular weight (MW) = 70,000] until systemic hematocrit (Hct) was reduced by 65%. A third step reduced Hct by 75% and was performed with the same solution [low viscosity (LV)] or a high-molecular-weight 6% Dextran 500 solution [MW = 500,000, high viscosity (HV)]. Final plasma viscosities were 1.4 and 2.2 cP (baseline of 1.2 cP). Hct was reduced to 11.2 ± 1.1% from 46.2 ± 1.5% for LV and to 11.9 ± 0.7% from 47.3 ± 2.1% for HV. HV produced a greater mean arterial blood pressure than LV. Functional capillary density (FCD) was substantially higher after HV (85 ± 12%) vs. LV (38 ± 30%) vs. baseline (100%).[Formula: see text] levels measured with Pd-porphyrin phosphorescence microscopy were not statistically changed from baseline until after the third hemodilution step. Wall shear rate (WSR) decreased in arterioles and venules after LV and only in arterioles after HV. Wall shear stress (WSR × plasma viscosity) was substantially higher after HV vs. LV. Increased mean arterial pressure and shear stress-dependent release of endothelium-derived relaxing factor are possible mechanisms that improved arteriolar and venular blood flow and FCD after HV vs. LV exchange protocols.

scholarly journals Assessment with clinical data of a coupled bio-hemodynamics numerical model to predict leukocyte adhesion in coronary arteries

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Umberto Ciri ◽  
Ruth L. Bennett ◽  
Rita Bhui ◽  
David S. Molony ◽  
Habib Samady ◽  
...  
Keyword(s):  
Shear Stress ◽  
Numerical Model ◽  
Wall Shear Stress ◽  
Coronary Arteries ◽  
Clinical Data ◽  
Leukocyte Adhesion ◽  
Three Dimensional ◽  
High Adhesion ◽  
Wall Shear ◽  
Stress Dependent

AbstractNumerical simulations of coupled hemodynamics and leukocyte transport and adhesion inside coronary arteries have been performed. Realistic artery geometries have been obtained for a set of four patients from intravascular ultrasound and angiography images. The numerical model computes unsteady three-dimensional blood hemodynamics and leukocyte concentration in the blood. Wall-shear stress dependent leukocyte adhesion is also computed through agent-based modeling rules, fully coupled to the hemodynamics and leukocyte transport. Numerical results have a good correlation with clinical data. Regions where high adhesion is predicted by the simulations coincide to a good approximation with artery segments presenting plaque increase, as documented by clinical data from baseline and six-month follow-up exam of the same artery. In addition, it is observed that the artery geometry and, in particular, the tortuosity of the centerline are a primary factor in determining the spatial distribution of wall-shear stress, and of the resulting leukocyte adhesion patterns. Although further work is required to overcome the limitations of the present model and ultimately quantify plaque growth in the simulations, these results are encouraging towards establishing a predictive methodology for atherosclerosis progress.

scholarly journals Venoarterial communication mediates arterial wall shear stress-induced maternal uterine vascular remodeling during pregnancy

2018 ◽  
Vol 315 (3) ◽  
pp. H709-H717 ◽  
Author(s):  
Nga Ling Ko ◽  
Maurizio Mandalà ◽  
Liam John ◽  
Aaron Gelinne ◽  
George Osol
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Vascular Remodeling ◽  
Uterine Artery ◽  
Complete Removal ◽  
No Synthase ◽  
Surgical Approaches ◽  
Wall Shear ◽  
Endothelial Nitric Oxide

Although expansive remodeling of the maternal uterine circulation during pregnancy is essential for maintaining uteroplacental perfusion and normal fetal growth, the underlying physiological mechanisms are not well understood. Using a rat model, surgical approaches were used to alter uterine hemodynamics and wall shear stress (WSS) to evaluate the effects of WSS and venoarterial communication (e.g., transfer of placentally derived growth signals from postplacental veins to preplacental arteries) on gestational uterine vascular remodeling. Changes in WSS secondary to ligation of the cervical but not the ovarian end of the main uterine artery and vein provoked significant expansive remodeling at the opposite end of both vessels, but only in pregnant animals. The ≈50% increase in lumen diameter (relative to the contralateral horn) was associated with an upregulation of total endothelial nitric oxide (NO) synthase expression and was abolished by in vivo NO synthase inhibition with N-nitro-l-arginine methyl ester. Complete removal of a venous segment adjacent to the uterine artery to eliminate local venous influences significantly attenuated the WSS-induced remodeling by about one-half ( P < 0.05). These findings indicate that, during pregnancy, 1) increased WSS stimulates uterine artery growth via NO signaling and 2) the presence of an adjacent vein is required for arterial remodeling to fully occur. NEW & NOTEWORTHY This study provides the first in vivo evidence for the importance of venous influences on arterial growth within the uteroplacental circulation.

Mass Transfer of LDL Based on Wall Shear Stress From FSI Simulation in Atherosclerotic Human Carotid Artery

2010 ◽  
Author(s):  
Sungho Kim ◽  
Don P. Giddens
Keyword(s):  
Shear Stress ◽  
Carotid Artery ◽  
Wall Shear Stress ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Mass ◽  
Black Blood ◽  
Ldl Particles ◽  
Wall Shear ◽  
Stress Dependent

Wall shear stress (WSS) distribution and low density lipoprotein (LDL) mass flux are simulated using a fluid-structure interaction (FSI) approach. T2 weighted black blood MRI images of a human left carotid artery are used for the arterial model construction, and the boundary conditions for FSI simulation are derived from phase contrast (PC) MR data. The endothelium is treated as a shear stress dependent, three pathways pore model for LDL particles. The computational results demonstrate that the region distal to an atherosclerotic plaque in the internal carotid artery experiences both low WSS and high mass and volume flux, which are hypothesized to be essential factors in progression of atherosclerosis.

Role of endothelial [Ca2+]i in activation of eNOS in pressurized arterioles by agonists and wall shear stress

2001 ◽  
Vol 281 (2) ◽  
pp. H606-H612 ◽  
Author(s):  
Zoltan Ungvari ◽  
Dong Sun ◽  
An Huang ◽  
Gabor Kaley ◽  
Akos Koller
Keyword(s):  
Skeletal Muscle ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
No Donor ◽  
A 23187 ◽  
Wall Shear ◽  
High Level

In cultured endothelial cells, Ca2+-dependent and -independent activation of nitric oxide (NO) synthesis to agonists and flow/wall shear stress (WSS) has been demonstrated. However, the presence and function of these pathways are less well known in microvessels that can be exposed to a high level of WSS. We hypothesized that the role of changes in endothelial intracellular calcium concentration ([Ca2+]i) is different in agonist- and WSS-induced release of NO. Thus changes in endothelial [Ca2+]i and diameter of intact pressurized (∼100 μm at 80 mmHg) gracilis skeletal muscle arterioles of rats were measured by fluorescent videomicroscopy. Acetylcholine (ACh) and increases in WSS (by increasing intraluminal flow) elicited dilations (maximum 91 ± 2% and 34 ± 4%) that could be inhibited by N ω-nitro-l-arginine methyl ester (l-NAME), a NO synthase blocker. In diameter-clamped arterioles, ACh caused substantial increases in the endothelial calcium fluorescence ratio (ERCa, maximum 43 ± 5%), which was significantly greater than changes in ERCa (maximum ∼10%) to increases in WSS. The Ca2+ ionophore A-23187 also substantially increased ERCa (maximum 38 ± 5%) and elicited significant l-NAME-sensitive arteriolar dilations (maximum 45 ± 7%). Intraluminal administration of the tyrosine kinase inhibitor genistein had no effect on dilations induced by ACh or the NO donor sodium nitroprusside, whereas it eliminated WSS-induced dilations. Collectively, our data suggest that, in endothelium of skeletal muscle arterioles, NO synthesis is activated by shear stress without a substantial increase in [Ca2+]i, most likely by activation of tyrosine kinase pathways, whereas NO release by ACh and A-23187 is associated with substantial increases in [Ca2+]i.

Endothelial regulation of wall shear stress and blood flow in skeletal muscle microcirculation

1991 ◽  
Vol 260 (3) ◽  
pp. H862-H868 ◽  
Author(s):  
A. Koller ◽  
G. Kaley
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Flow Velocity ◽  
Cremaster Muscle ◽  
Skeletal Muscle Microcirculation ◽  
Wall Shear ◽  
Arteriolar Diameter ◽  
Dependent Mechanism

In the presence of intact endothelium, in control conditions, calculated wall shear rate (WSR) (means +/- SE: 2,658 +/- 123 s-1; n = 21) was independent of arteriolar diameter (16.2-27.2 microns; correlation coefficient: r = 0.12, P greater than 0.05) in cremaster muscle of pentobarbital-anesthetized rats. An increase in blood flow velocity (due to parallel arteriolar occlusion) elicited a significant increase in WSR (to 4,981 +/- 253 s-1) followed by a delayed (6-15 s) increase in diameter (from: 22.5 +/- 0.6 to 29.5 +/- 0.8 microns), which consequently resulted in a significant decrease in WSR (to 3,879 +/- 203 s-1). As a result of the increased flow velocity and dilation, calculated arteriolar blood flow increased by 230%. After impairment of the endothelium of arterioles by a light-dye technique, basal WSR became significantly higher (3,604 +/- 341 s-1), and despite a greater increase in WSR (10,360 +/- 1,471 s-1) the dilation was absent. Now an inverse linear correlation was found between arteriolar diameter and WSR both before (r = 0.58, P less than 0.05) and during increased flow velocity conditions (r = 0.85, P less than 0.05). Also, arteriolar blood flow that was already less after impairment of endothelium increased by only 66% during the period of increased flow velocity due to the absence of dilation. Results suggest that an increase in wall shear stress is the stimulus for the endothelium-dependent mechanism that elicits "flow dependent" arteriolar dilation.(ABSTRACT TRUNCATED AT 250 WORDS)

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