Effect of pressure on hydraulic conductivity of endothelial monolayers: role of endothelial cleft shear stress

1999 ◽  
Vol 87 (1) ◽  
pp. 261-268 ◽  
Author(s):  
John M. Tarbell ◽  
Lucas Demaio ◽  
Mark M. Zaw
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Hydraulic Conductivity ◽  
Elevated Pressure ◽  
Transmural Pressure ◽  
Luminal Surface ◽  
Aortic Endothelial Cells ◽  
Effect Of Pressure ◽  
Steady State Levels ◽  
Transmural Flow

Significant changes in transvascular pressure occur in pulmonary hypertension, microgravity, and many other physiological and pathophysiological circumstances. Using bovine aortic endothelial cells grown on porous, rigid supports, we demonstrate that step changes in transmural pressure of 10, 20, and 30 cmH2O induce significant elevations in endothelial hydraulic conductivity ( L p) that require 5 h to reach new steady-state levels. The increases in L p can be reversed by addition of a stable cAMP analog (dibutyryl cAMP), and the increases in L pin response to pressure can be inhibited significantly with nitric oxide synthase inhibitors ( N G-monomethyl-l-arginine and nitro-l-arginine methyl ester). The increase in L p was not due to pressure-induced stretch because the endothelial cell (EC) support was rigid. It is unlikely that the increase in L p was due to a direct effect of pressure because exposure of the cells to elevated pressure (25 cmH2O) for 4 h had no effect on the volume flux driven by a transmural pressure of 10 cmH2O. We hypothesize that elevated endothelial cleft shear stress induced by elevated transmural flow in response to elevated pressure stimulates the increase in L p through a nitric oxide-cAMP-dependent mechanism. This is consistent with recent studies of the effects of shear stress on the luminal surface of ECs. We provide simple estimates of endothelial cleft shear stress, which suggest magnitudes comparable to those imposed by blood flow on the luminal surface of ECs.

The Effect of Pressure on the Non-Newtonian Behavior of Polymer Blended Petroleum Oils

1969 ◽  
Vol 91 (3) ◽  
pp. 459-462 ◽  
Author(s):  
J. D. Novak ◽  
W. O. Winer
Keyword(s):  
Shear Stress ◽  
Shear Strain ◽  
Atmospheric Pressure ◽  
Weight Percent ◽  
Elevated Pressure ◽  
Base Oil ◽  
Effect Of Pressure ◽  
Elevated Pressures ◽  
Capillary Type ◽  
Newtonian Behavior

The shear dependence of polymer containing oils at elevated pressure was observed in a capillary-type viscometer and is reported. Recoverable shear strain was not observed at elevated pressures but was observed at atmospheric pressure in the blends at the same shear stress. The fluids examined included a paraffinic base oil (B), B plus four and eight weight percent methacrylate, B plus four weight percent styrene, a naphthenic base oil (F), and F plus four weight percent methacrylate.

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.

IκBα-dependent regulation of low-shear flow-induced NF-κB activity: role of nitric oxide

2003 ◽  
Vol 284 (4) ◽  
pp. C1039-C1047 ◽  
Author(s):  
Sumathy Mohan ◽  
Masao Hamuro ◽  
George P. Sorescu ◽  
Koichi Koyoma ◽  
Eugene A. Sprague ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Shear Flow ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Aortic Endothelial Cells ◽  
Low Shear Stress ◽  
Endothelial Nitric Oxide ◽  
Low Shear

We have investigated the role of inhibitor κBα (IκBα) in the activation of nuclear factor κB (NF-κB) observed in human aortic endothelial cells (HAEC) undergoing a low shear stress of 2 dynes/cm2. Low shear for 6 h resulted in a reduction of IκBα levels, an activation of NF-κB, and an increase in κB-dependent vascular cell adhesion molecule 1 (VCAM-1) mRNA expression and endothelial-monocyte adhesion. Overexpression of IκBα in HAEC attenuated all of these shear-induced responses. These results suggest that downregulation of IκBα is the major factor in the low shear-induced activation of NF-κB in HAEC. We then investigated the role of nitric oxide (NO) in the regulation of IκBα/NF-κB. Overexpression of endothelial nitric oxide synthase (eNOS) inhibited NF-κB activation in HAEC exposed to 6 h of low shear stress. Addition of the structurally unrelated NO donors S-nitrosoglutathione (300 μM) or sodium nitroprusside (1 mM) before low shear stress significantly increased cytoplasmic IκBα and concomitantly reduced NF-κB binding activity and κB-dependent VCAM-1 promoter activity. Together, these data suggest that NO may play a major role in the regulation of IκBα levels in HAEC and that the application of low shear flow increases NF-κB activity by attenuating NO generation and thus IκBα levels.

Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress

1995 ◽  
Vol 269 (6) ◽  
pp. C1371-C1378 ◽  
Author(s):  
M. Uematsu ◽  
Y. Ohara ◽  
J. P. Navas ◽  
K. Nishida ◽  
T. J. Murphy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Nitric Oxide Synthase ◽  
Mrna Expression ◽  
K Channel ◽  
Shear Stresses ◽  
Aortic Endothelial Cells ◽  
Oxide Synthase

Shear stress enhances expression of Ca(2+)-calmodulin-sensitive endothelial cell nitric oxide synthase (ecNOS) mRNA and protein in bovine aortic endothelial cells (BAEC). The present studies were performed to investigate mechanisms responsible for regulation of ecNOS mRNA expression by shear stress and to determine if this induction of ecNOS mRNA is accompanied by an enhanced nitric oxide (NO) production. Shear stresses of 15 dyn/cm2 for 3-24 h resulted in a two- to threefold increase of ecNOS mRNA content quantified by Northern analysis in BAEC. Shear stresses (1.2-15 dyn/cm2) for 3 h resulted in an induction of ecNOS mRNA in a dose-dependent manner. In human aortic endothelial cells, shear stresses of 15 dyn/cm2 for 3 h also resulted in ecNOS mRNA induction. In BAEC, this induction in ecNOS mRNA was prevented by coincubation with actinomycin D (10 micrograms/ml). The K+ channel antagonist tetraethylammonium chloride (3 mM) prevented increase in ecNOS mRNA in response to shear stress. The ecNOS promotor contains putative binding domains for AP-1 complexes, potentially responsive to activation of protein kinase C (PKC). However, selective PKC inhibitor calphostin C (100 nM) did not inhibit ecNOS induction by shear stress. Finally, production of nitrogen oxides under both basal conditions and in response to the calcium ionophore A-23187 (1 microM) by BAEC exposed to shear stress was increased approximately twofold compared with cells not exposed to shear stress. These data suggest that ecNOS mRNA expression is regulated by K+ channel opening, but not by activation of PKC, and that shear not only enhances ecNOS mRNA expression but increases capacity of endothelial cells to release NO.

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

scholarly journals Endothelium-specific sepiapterin reductase deficiency in DOCA-salt hypertension

2012 ◽  
Vol 302 (11) ◽  
pp. H2243-H2249 ◽  
Author(s):  
Ji Youn Youn ◽  
Ting Wang ◽  
John Blair ◽  
Karine M. Laude ◽  
Jeong-Ho Oak ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Oxidase Inhibitor ◽  
Aortic Endothelial Cells ◽  
Sepiapterin Reductase ◽  
Enos Uncoupling ◽  
Induced Hypertension ◽  
Salt Hypertension ◽  
Endothelial Nitric Oxide ◽  
Aortic Endothelial

The endothelial nitric oxide synthase (eNOS) requires tetrahydrobiopterin (H4B) as a cofactor and, in its absence, produces superoxide (O2·−) rather than nitric oxide (NO·), a condition referred to as eNOS uncoupling. DOCA-salt-induced hypertension is associated with H4B oxidation and uncoupling of eNOS. The present study investigated whether administration of sepiapterin or H4B recouples eNOS in DOCA-salt hypertension. Bioavailable NO· detected by electron spin resonance was markedly reduced in aortas of DOCA-salt hypertensive mice. Preincubation with sepiapterin (10 μmol/l for 30 min) failed to improve NO· bioavailability in hypertensive aortas while it augmented NO· production from control vessels, implicating a hypertension-associated deficiency in sepiapterin reductase (SPR), the rate-limiting enzyme for sepiapterin conversion to H4B. Indeed, a decreased SPR expression was observed in aortic endothelial cells, but not in endothelium-denuded aortic remains, implicating an endothelium-specific SPR deficiency. Administration of hypertensive aortas with H4B (10 μmol/l, 30 min) partially restored vascular NO· production. Combined administration of H4B and the NADPH oxidase inhibitor apocynin (100 μmol/l, 30 min) fully restored NO· bioavailability while reducing O2·− production. In angiotensin II-induced hypertension, however, aortic endothelial SPR expression was not affected. In summary, administration of sepiapterin is not effective in recoupling eNOS in DOCA-salt hypertension, due to an endothelium-specific loss in SPR, whereas coadministration of H4B and apocynin is highly efficient in recoupling eNOS. This is consistent with our previous observations that in angiotensin II hypertension, endothelial deficiency in dihydrofolate reductase is alternatively responsible for uncoupling of eNOS. Taken together, these data indicate that strategies specifically targeting at different H4B metabolic enzymes might be necessary in restoring eNOS function in different types of hypertension.

scholarly journals Differential mechanisms of inhibition of glyceraldehyde-3-phosphate dehydrogenase by S-nitrosothiols and NO in cellular and cell-free conditions

2010 ◽  
Vol 299 (4) ◽  
pp. H1212-H1219 ◽  
Author(s):  
Katarzyna A. Broniowska ◽  
Neil Hogg
Keyword(s):  
Nitric Oxide ◽  
Signaling Mechanism ◽  
Aortic Endothelial Cells ◽  
Signaling Specificity ◽  
Physiological Conditions ◽  
Irreversible Inhibition ◽  
Bovine Aortic Endothelial Cells ◽  
Mechanism Of Inhibition ◽  
Dependent Inhibition ◽  
Inhibition Pattern

S-nitrosothiols are nitric oxide (NO)-derived molecules found in biological systems. They have been variously discussed as both NO reservoirs and as major actors in NO-dependent, but cGMP-independent, signal transduction. Although S-nitrosation of specific cysteine residues has been suggested to represent a novel redox-based signaling mechanism, the exact mechanisms of S-nitrosothiol formation under (patho)physiological conditions and the determinants of signaling specificity have not yet been established. Here we examined the sensitivity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to inhibition by S-nitrosocysteine (CysNO) and NO both intracellularly and in isolation. Bovine aortic endothelial cells (BAECs) and purified GAPDH preparations were treated with CysNO or NO, and enzymatic activity was monitored. Intracellular GAPDH was irreversibly inhibited upon CysNO administration, whereas treatment with NO resulted in a DTT-reversible inhibition of the enzyme. Purified GAPDH was inhibited by both CysNO and NO, but the inhibition pattern was diametrically opposite to that observed in the cells; CysNO-dependent inhibition was reversed with DTT, whereas NO-dependent inhibition was not. In the presence of GSH, NO inhibited purified GAPDH in a DTT-reversible way. Our data suggest that in response to CysNO treatment, cellular GAPDH undergoes S-nitrosation, which results in an irreversible inhibition of the enzyme under turnover conditions. In contrast, NO inhibits the enzyme via oxidative mechanisms that do not involve S-nitrosation and are reversible. In summary, our data show that GAPDH is a target for CysNO- and NO-dependent inhibition; however, these two agents inhibit the enzyme via different mechanisms both inside the cell and in isolation. Additionally, the differences observed between the cellular system and purified protein strongly imply that the intracellular environment dictates the mechanism of inhibition.

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