Regulation of nitric oxide andbcl-2 expression by shear stress in human osteoarthritic chondrocytes in vitro

2003 ◽  
Vol 90 (1) ◽  
pp. 80-86 ◽  
Author(s):  
Mel S. Lee ◽  
Michael C.D. Trindade ◽  
Takashi Ikenoue ◽  
Stuart B. Goodman ◽  
David J. Schurman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Osteoarthritic Chondrocytes

Effects of shear stress on nitric oxide and matrix protein gene expression in human osteoarthritic chondrocytes in vitro

2002 ◽  
Vol 20 (3) ◽  
pp. 556-561 ◽  
Author(s):  
Mel S. Lee ◽  
Michael C. D. Trindade ◽  
Takashi Ikenoue ◽  
David J. Schurman ◽  
Stuart B. Goodman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Shear Stress ◽  
Matrix Protein ◽  
Protein Gene ◽  
Matrix Protein Gene ◽  
Osteoarthritic Chondrocytes

scholarly journals Pentoxifylline attenuation of experimental hepatopulmonary syndrome

2007 ◽  
Vol 102 (3) ◽  
pp. 949-955 ◽  
Author(s):  
Junlan Zhang ◽  
Yiqun Ling ◽  
Liping Tang ◽  
Bao Luo ◽  
Balu K. Chacko ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Hepatopulmonary Syndrome ◽  
Microvascular Endothelial Cells ◽  
Enos Expression ◽  
Akt Activation ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Tnf Α

Hepatopulmonary syndrome (HPS) following rat common bile duct ligation results from pulmonary molecular changes that may be influenced by circulating TNF-α and increased vascular shear stress, through activation of NF-κB or Akt. Increased pulmonary microvascular endothelin B (ETB) receptor and endothelial nitric oxide synthase (eNOS) levels contribute to nitric oxide production and the development of experimental HPS. Pentoxifylline (PTX), a phosphodiesterase and nonspecific TNF-α inhibitor, ameliorates experimental HPS when begun before hepatic injury. However, how PTX influences the molecular events associated with initiation of experimental HPS after liver injury is established is unknown. We assessed the effects of PTX on the molecular and physiological features of HPS in vivo and on shear stress or TNF-α-mediated events in rat pulmonary microvascular endothelial cells in vitro. PTX significantly improved HPS without altering portal or systemic hemodynamics and downregulated pulmonary ETB receptor levels and eNOS expression and activation. These changes were associated with a reduction in circulating TNF levels and NF-κB activation and complete inhibition of Akt activation. In rat pulmonary microvascular endothelial cells, PTX inhibited shear stress-induced ETB receptor and eNOS expression and eNOS activation. These effects were also associated with inhibition of Akt activation and were reproduced by wortmanin. In contrast, TNF-α had no effects on endothelial ETB and eNOS alterations in vitro. PTX has direct effects in the pulmonary microvasculature, likely mediated through Akt inhibition, that ameliorate experimental HPS.

scholarly journals Shear stress blunts tubuloglomerular feedback partially mediated by primary cilia and nitric oxide at the macula densa

2015 ◽  
Vol 309 (7) ◽  
pp. R757-R766 ◽  
Author(s):  
Lei Wang ◽  
Chunyu Shen ◽  
Haifeng Liu ◽  
Shaohui Wang ◽  
Xinshan Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Primary Cilia ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Hydraulic Pressure ◽  
No Production ◽  
Tubular Flow ◽  
Nitric Oxide Synthase 1

The present study tested whether primary cilia on macula densa serve as a flow sensor to enhance nitric oxide synthase 1 (NOS1) activity and inhibit tubuloglomerular feedback (TGF). Isolated perfused macula densa was loaded with calcein red and 4,5-diaminofluorescein diacetate to monitor cell volume and nitric oxide (NO) generation. An increase in tubular flow rate from 0 to 40 nl/min enhanced NO production by 40.0 ± 1.2%. The flow-induced NO generation was blocked by an inhibitor of NOS1 but not by inhibition of the Na/K/2Cl cotransporter or the removal of electrolytes from the perfusate. NO generation increased from 174.8 ± 21 to 276.1 ± 24 units/min in cultured MMDD1 cells when shear stress was increased from 0.5 to 5.0 dynes/cm2. The shear stress-induced NO generation was abolished in MMDD1 cells in which the cilia were disrupted using a siRNA to ift88. Increasing the NaCl concentration of the tubular perfusate from 10 to 80 mM NaCl in the isolated perfused juxtaglomerular preparation reduced the diameter of the afferent arteriole by 3.8 ± 0.1 μm. This response was significantly blunted to 2.5 ± 0.2 μm when dextran was added to the perfusate to increase the viscosity and shear stress. Inhibition of NOS1 blocked the effect of dextran on TGF response. In vitro, the effects of raising perfusate viscosity with dextran on tubular hydraulic pressure were minimized by reducing the outflow resistance to avoid stretching of tubular cells. These results suggest that shear stress stimulates primary cilia on the macula densa to enhance NO generation and inhibit TGF responsiveness.

scholarly journals Direct, real-time measurement of shear stress-induced nitric oxide produced from endothelial cells in vitro

Nitric Oxide ◽  
2010 ◽  
Vol 23 (4) ◽  
pp. 335-342 ◽  
Author(s):  
Allison M. Andrews ◽  
Dov Jaron ◽  
Donald G. Buerk ◽  
Patrick L. Kirby ◽  
Kenneth A. Barbee
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Real Time ◽  
Time Measurement ◽  
Real Time Measurement

scholarly journals Myofiber stretch induces tensile and shear deformation of muscle stem cells in their native niche

2020 ◽  
Author(s):  
Mohammad Haroon ◽  
Jenneke Klein-Nulend ◽  
Astrid D. Bakker ◽  
Jianfeng Jin ◽  
Carla Offringa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Ex Vivo ◽  
Mechanical Forces ◽  
Fluid Shear ◽  
Muscle Stem Cells ◽  
Pulsating Fluid

ABSTRACTBackgroundMuscle stem cells (MuSCs) are requisite for skeletal muscle regeneration and homeostasis. Proper functioning of MuSCs, including activation, proliferation, and fate decision, is determined by an orchestrated series of events and communication between MuSCs and their niche consisting of the host myofiber and neighbouring cells. A multitude of biochemical stimuli are known to regulate fate and function of MuSCs. However, in addition to biochemical factors, it is conceivable that MuSCs residing between basal lamina and sarcolemma of myofibers are subjected to mechanical forces during muscle stretch-shortening cycles due to myofascial connections between MuSCs and myofibers. MuSCs have been shown to respond to mechanical forces in vitro but it remains to be proven whether physical forces are also exerted on MuSCs in their native niche and whether they contribute to the functioning and fate of MuSCs.MethodsMuSCs deformation in their native niche resulting from mechanical loading of ex vivo myofiber bundles were visualized utilizing mT/mG double-fluorescent Cre-reporter mouse and multiphoton microscopy. MuSCs were subjected to 1 hour pulsating fluid shear stress with a peak shear stress rate of 8.8 Pa/s. After treatment, nitric oxide and mRNA expression levels of genes involved in regulation of MuSC proliferation and differentiation were determined.ResultsEx vivo stretching of extensor digitorum longus and soleus myofiber bundles caused compression as well as tensile and shear deformation of MuSCs in their niche. MuSCs responded to pulsating fluid shear stress in vitro with increased nitric oxide production and an upward trend in iNOS mRNA levels, while nNOS expression was unaltered. Pulsating fluid shear stress enhanced gene expression of c-Fos, Cdk4, and IL-6, while expression of Wnt1, MyoD, Myog, Wnt5a, COX2, Rspo1, Vangl2, Wnt10b, and MGF remained unchanged.ConclusionsWe conclude that MuSCs in their native niche are subjected to force-induced deformations due to myofiber stretch-shortening. Moreover, MuSCs are mechanoresponsive as evident by pulsating fluid shear stress-mediated expression of factors by MuSCs known to promote proliferation.

Regulation of capillary hydraulic conductivity in response to an acute change in shear

2005 ◽  
Vol 289 (5) ◽  
pp. H2126-H2135 ◽  
Author(s):  
Min-ho Kim ◽  
Norman R. Harris ◽  
John M. Tarbell
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Hydraulic Conductivity ◽  
Flow Shear ◽  
Fluid Filtration ◽  
Acute Change ◽  
Acute Changes ◽  
Mesenteric Microvessels

The effects of mechanical perturbations (shear stress, pressure) on microvascular permeability primarily have been examined in micropipette-cannulated vessels or in endothelial monolayers in vitro. The objective of this study is to determine whether acute changes in blood flow shear stress might influence measurements of hydraulic conductivity ( Lp) in autoperfused microvessels in vivo. Rat mesenteric microvessels were observed via intravital microscopy. Occlusion of a third-order arteriole with a micropipette was used to divert and increase flow through a nonoccluded capillary or fourth-order arteriolar branch. Transvascular fluid filtration rate in the branching vessel was measured with a Landis technique. Flow (shear)-induced increases in Lp disappeared within 20–30 s of the removal of the shear and could be eliminated with nitric oxide synthase inhibition. The shear-induced increase in Lp was greater in capillaries compared with terminal arterioles. An acute change in shear may regulate Lp by a nitric oxide-dependent mechanism that displays heterogeneity within a microvascular network.

scholarly journals Endothelial pulsatile shear stress is a backstop for COVID-19

2020 ◽  
Vol 4 (4) ◽  
pp. 391-399
Author(s):  
Marvin A. Sackner ◽  
Jose A. Adams
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Physical Inactivity ◽  
Muscular Activity ◽  
The Body ◽  
Diverse Populations ◽  
Extensive Investigation ◽  
Pulsatile Shear Stress

There has not been any means to inhibit replication of the SARS-CoV-2 virus responsible for the rapid, deadly spread of the COVID-19 pandemic and an effective, safe, tested across diverse populations vaccine still requires extensive investigation. This review deals with the repurpose of a wellness technology initially fabricated for combating physical inactivity by increasing muscular activity. Its action increases pulsatile shear stress (PSS) to the endothelium such that the bioavailability of nitric oxide (NO) and other mediators are increased throughout the body. In vitro evidence indicates that NO inhibits SARS-CoV-2 virus replication but there are no publications of NO delivery to the virus in vivo. It will be shown that increased PSS has potential in vivo to exert anti-viral properties of NO as well as to benefit endothelial manifestations of COVID-19 thereby serving as a safe and effective backstop.

Evidence of nitric oxide, a flow-dependent factor, being a trigger of liver regeneration in rats

1998 ◽  
Vol 76 (12) ◽  
pp. 1072-1079 ◽  
Author(s):  
H Helen Wang ◽  
W Wayne Lautt
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Cultured Cells ◽  
Portal Blood Flow ◽  
Liver Weight ◽  
Proliferative Effect

The hypothesis tested was that the hemodynamic consequence of partial hepatectomy (PHX) triggers the cascade of events that leads to liver regeneration. After PHX, all the portal flow must go through the remaining vascular bed, thus producing increased shear stress and release of nitric oxide (NO), which then initiates the next stages of the regeneration process. As an index of triggering of the regeneration cascade, we used an in vitro bioassay detecting the appearance of proliferating factors (PFs; various growth factors, cytokines, and hormones) in plasma 4 h after two-thirds PHX in rats. PF levels, assessed using proliferation of cultured hepatocytes, were elevated in two-thirds PHX rats, fully blocked by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), and restored by L-arginine. L-NAME inhibited liver weight restoration at 48 h but resulted in high mortality. L-NAME lacked toxic effects in non-PHX rats. NO was directly antiproliferative on cultured cells, suggesting that the proliferative effect of NO in vivo was secondary to the activation of other proliferative stimuli. The data support the hypothesis that vascular shear stress induced release of NO following PHX serves as a primary trigger to initiate the regeneration process.Key words: shear stress, portal blood flow, hyperplasia, hepatic partial hepatectomy.

Human recombinant erythropoietin alters the flow-dependent vasodilatation of in vitro perfused rat mesenteric arteries with unbalanced endothelial endothelin-1 / nitric oxide ratio

2011 ◽  
Vol 89 (6) ◽  
pp. 435-443 ◽  
Author(s):  
Tlili Barhoumi ◽  
Isabelle Jallat ◽  
Alain Berthelot ◽  
Pascal Laurant
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Inhibitory Effect ◽  
Mesenteric Arteries ◽  
Recombinant Erythropoietin ◽  
Resistance Arteries ◽  
Vascular Effects ◽  
Human Recombinant Erythropoietin ◽  
Endothelin 1

Chronic use of human recombinant erythropoietin (r-HuEPO) is accompanied by serious vascular side effects related to the rise in blood viscosity and shear stress. We investigated the direct effects of r-HuEPO on endothelium and nitric oxide (NO)-dependent vasodilatation induced by shear stress of cannulated and pressurized rat mesenteric resistance arteries. Intravascular flow was increased in the presence or absence of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME; 10−4 mol/L). In the presence of r-HuEPO, the flow-dependent vasodilatation was attenuated, while L-NAME completely inhibited it. The association of r-HuEPO and L-NAME caused a vasoconstriction in response to the rise in intravascular flow. Bosentan (10−5 mol/L), an inhibitor of endothelin-1 (ET-1) receptors, corrected the attenuated vasodilatation observed with r-HuEPO and inhibited the vasoconstriction induced by flow in the presence of r-HuEPO and L-NAME. r-HuEPO and L-NAME exacerbated ET-1 vasoconstriction. At shear stress values of 2 and 14 dyn/cm2 (1 dyn = 10–5 N), cultured EA.hy926 endothelial cells incubated with r-HuEPO, L-NAME, or both released greater ET-1 than untreated cells. In conclusion, r-HuEPO diminishes flow-induced vasodilatation. This inhibitory effect seems to implicate ET-1 release. NO withdrawal exacerbates the vascular effects of ET-1 in the presence of r-HuEPO. These findings support the importance of a balanced endothelial ET-1:NO ratio to avoid the vasopressor effects of r-HuEPO.

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