Modulation of endothelial nitric oxide synthase expression by red blood cell aggregation

2004 ◽  
Vol 286 (1) ◽  
pp. H222-H229 ◽  
Author(s):  
Oguz K. Baskurt ◽  
Ozlem Yalcin ◽  
Sadi Ozdem ◽  
Jonathan K. Armstrong ◽  
Herbert J. Meiselman
Keyword(s):  
Nitric Oxide ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Cell Aggregation ◽  
Shear Stresses ◽  
Control Mechanisms ◽  
Vascular Control ◽  
Arterial Blood ◽  
Rbc Aggregation ◽  
Endothelial Nitric Oxide

The effects of enhanced red blood cell (RBC) aggregation on nitric oxide (NO)-dependent vascular control mechanisms have been investigated in a rat exchange transfusion model. RBC aggregation for cells in native plasma was increased via a novel method using RBCs covalently coated with a 13-kDa poloxamer copolymer (Pluronic F-98); control experiments used RBCs coated with a nonaggregating 8.4-kDa poloxamer (Pluronic F-68). Rats exchange transfused with aggregating RBC suspensions demonstrated significantly enhanced RBC aggregation throughout the 5-day follow-up period, with mean arterial blood pressure increasing gradually over this period. Arterial segments (≈300 μm in diameter) were isolated from gracilis muscle on the fifth day and mounted between two glass micropipettes in a special chamber equipped with pressure servo-control system. Dose-dependent dilation by ACh and flow-mediated dilation of arterial segments pressurized to 30 mmHg and preconstricted to 45–55% of the original diameter by phenylephrine were significantly blunted in rats with enhanced RBC aggregation. Both responses were totally abolished by nonspecific NO synthase (NOS) inhibitor ( Nω-nitro-l-arginine methyl ester) treatment of arterial segments, indicating that the responses were NO related. Additionally, expression of endothelial NOS protein was found to be decreased in muscle samples obtained from rats exchanged with aggregating cell suspensions. These results imply that enhanced RBC aggregation results in suppressed expression of NO synthesizing mechanisms, thereby leading to altered vasomotor tonus; the mechanisms involved most likely relate to decreased wall shear stresses due to decreased blood flow and/or increased axial accumulation of RBCs.

Effects of red blood cell aggregation on myocardial hematocrit gradient using two approaches to increase aggregation

2006 ◽  
Vol 290 (2) ◽  
pp. H765-H771 ◽  
Author(s):  
Ozlem Yalcin ◽  
Funda Aydin ◽  
Pinar Ulker ◽  
Mehmet Uyuklu ◽  
Firat Gungor ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Control Level ◽  
Three Dimensional ◽  
Cell Aggregation ◽  
Plasma Viscosity ◽  
Covalent Attachment ◽  
Erythrocyte Aggregation ◽  
Rbc Aggregation ◽  
A New Technique

The normal transmyocardial tissue hematocrit distribution (i.e., subepicardial greater than subendocardial) is known to be affected by red blood cell (RBC) aggregation. Prior studies employing the use of infused large macromolecules to increase erythrocyte aggregation are complicated by both increased plasma viscosity and dilution of plasma. Using a new technique to specifically alter the aggregation behavior by covalent attachment of Pluronic F-98 to the surface of the RBC, we have determined the effects of only enhanced aggregation (i.e., Pluronic F-98-coated RBCs) versus enhanced aggregation with increased plasma viscosity (i.e., an addition of 500 kDa dextran) on myocardial tissue hematocrit in rapidly frozen guinea pig hearts. Although both approaches equally increased aggregation, tissue hematocrit profiles differed markedly: 1) when Pluronic F-98-coated cells were used, the normal transmyocardial gradient was abolished, and 2) when dextran was added, the hematocrit remained at subepicardial levels for about one-half the thickness of the myocardium and then rapidly decreased to the control level in the subendocardial layer. Our results indicate that myocardial hematocrit profiles are sensitive to both RBC aggregation and to changes of plasma viscosity associated with increased RBC aggregation. Furthermore, they suggest the need for additional studies to explore the mechanisms affecting RBC distribution in three-dimensional vascular beds.

scholarly journals Photoacoustic ultrasound spectroscopy for assessing red blood cell aggregation and oxygenation

2021 ◽  
Author(s):  
Michael C. Kolios
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Aggregate Size ◽  
Cell Aggregation ◽  
Frequency Domain Analysis ◽  
Spectral Slope ◽  
Spectral Parameters ◽  
Oxygen Saturation Level ◽  
Oxygenation Level ◽  
Rbc Aggregation

Red blood cell (RBC) aggregation and oxygenation are important markers for a variety of blood disorders. No current technique is capable of simultaneously measuring aggregation/oxygenation levels noninvasively. We propose using photoacoustic ultrasound spectroscopy (PAUS) for assessing both phenomena. This technique relies on frequency-domain analysis of the PA signals by extracting parameters such as the ultrasound spectral slope and the midband fit. To investigate the effect of hematocrit, aggregation, and oxygenation levels on PAUS parameters, a Monte Carlo-based theoretical model and an experimental protocol using porcine RBCs were developed. The samples were illuminated at 750 and 1064 nm and changes in the PAUS parameters were compared to the oxygen-dependent optical absorption coefficients to assess the oxygenation level. Good agreement between the theoretical and experimental spectral parameters was obtained for the spectral slope of the nonaggregated spectra (∼0.3  dB/MHz∼0.3  dB/MHz). The experimental midband fit increased by ∼5  dB∼5  dB for the largest aggregate size. Based on the analysis of the PA signals, the oxygen saturation level of the most aggregated sample was >20%>20% greater than the nonaggregated sample. The results provide a framework for using PA signals’ spectroscopic parameters for monitoring the aggregation and oxygenation levels of RBCs.

scholarly journals Red blood cell (RBC) aggregation and its influence on non-Newtonian nature of blood in microvasculature

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Chitra Murali ◽  
Perumal Nithiarasu
Keyword(s):  
Blood Flow ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Cell Aggregation ◽  
Time Dependent ◽  
Shear Rates ◽  
Red Blood Cell Aggregation ◽  
Significant Difference ◽  
Rbc Aggregation ◽  
Rouleaux Formation

AbstractA robust computational model is proposed to investigate the non-Newtonian nature of blood flow due to rouleaux formation in microvasculature. The model consists of appropriate forces responsible for red blood cell (RBC) aggregation in the microvasculature, tracking of RBCs, and coupling between plasma flow and RBCs. The RBC aggregation results have been compared against the available data. The importance of different hydrodynamic forces on red blood cell aggregation has been delineated by comparing the time dependent path of the RBCs. The rheological changes to the blood flow have been investigated under different shear rates and hematocrit values and quantified with and without RBC aggregation. The results obtained in terms of wall shear stress (WSS) and blood viscosity indicate a significant difference between Newtonian and powerlaw fluid assumptions.

scholarly journals Red blood cell endothelial nitric oxide synthase does not modulate red blood cell storage hemolysis

Transfusion ◽  
2012 ◽  
Vol 53 (5) ◽  
pp. 981-989 ◽  
Author(s):  
Tamir Kanias ◽  
Ling Wang ◽  
Ashley Lippert ◽  
Daniel B. Kim-Shapiro ◽  
Mark T. Gladwin
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Endothelial Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Cell Storage

Effects of nitric oxide on red blood cell deformability

2003 ◽  
Vol 284 (5) ◽  
pp. H1577-H1584 ◽  
Author(s):  
Melek Bor-Kucukatay ◽  
Rosalinda B. Wenby ◽  
Herbert J. Meiselman ◽  
Oguz K. Baskurt
Keyword(s):  
Nitric Oxide ◽  
Blood Cell ◽  
Guanylate Cyclase ◽  
Red Blood Cell ◽  
Soluble Guanylate Cyclase ◽  
Shear Stresses ◽  
No Donors ◽  
Nos Inhibitors ◽  
Deta Nonoate ◽  
Rbc Deformability

In addition to its known action on vascular smooth muscle, nitric oxide (NO) has been suggested to have cardiovascular effects via regulation of red blood cell (RBC) deformability. The present study was designed to further explore this possibility. Human RBCs in autologous plasma were incubated for 1 h with NO synthase (NOS) inhibitors [ N ω-nitro-l-arginine methyl ester (l-NAME) and S-methylisothiourea], NO donors [sodium nitroprusside (SNP) and diethylenetriamine (DETA)-NONOate], an NO precursor (l-arginine), soluble guanylate cyclase inhibitors (1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one and methylene blue), and a potassium channel blocker [triethylammonium (TEA)]. After incubation, RBC deformability at various shear stresses was determined by ektacytometry. Both NOS inhibitors significantly reduced RBC deformability above a threshold concentration, whereas the NO donors increased deformability at optimal concentrations. NO donors, as well as the NO precursor l-arginine and the potassium blocker TEA, were able to reverse the effects of NOS inhibitors. Guanylate cyclase inhibition reduced RBC deformation, with both SNP and DETA-NONOate able to reverse this effect. These results thus indicate the importance of NO as a determinant of RBC mechanical behavior and suggest its regulatory role for normal RBC deformability.

scholarly journals High frequency photoacoustic detection of red blood cell aggregation

2021 ◽  
Author(s):  
Fayruz Kibria
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
High Frequency ◽  
Photoacoustic Imaging ◽  
Low Frequency ◽  
Cell Aggregation ◽  
Center Frequency ◽  
Photoacoustic Detection ◽  
Rbc Aggregation

Red blood cell (RBC) aggregation was correctly reported in early 1768 as the increased deposition for blood to form spots of red in pathological conditions. However only recently have there been advances in technology to allow possible detection of RBC aggregation in vivo. Photoacoustic imaging (PA) shows a promising future in the detection of simultaneous in vivo RBC aggregation and oxygen saturation. This work presents, for the first time, the results of investigating aggregated RBCs using high frequency (> 20 MHz) photoacoustic (PA) imaging. Aggregation was induced by using 3% w/v concentration of 70 kDa Dextran and PA measurements were taken by a 25 MHz center frequency transducer. It was found that the spectral slope (SS) of the photoacoustic signals decreased by ~0.25 dB/MHz with RBC aggregation. The results are consistent with the findings of low frequency PA RBC aggregation study which also reported decrease in SS with increased aggregation.

scholarly journals On the use of photoacoustics to detect red blood cell aggregation

2021 ◽  
Author(s):  
Michael C. Kolios
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Spectral Power ◽  
Aggregate Size ◽  
Cell Aggregation ◽  
Dominant Frequency ◽  
Red Blood Cell Aggregation ◽  
Theoretical Predictions ◽  
Rbc Aggregation ◽  
Simulation Results

The feasibility of detecting red blood cell (RBC) aggregation with photoacoustics (PAs) was investigated theoretically and experimentally using human and porcine RBCs. The theoretical PA signals and spectra generated from such samples were examined for several hematocrit levels and aggregates sizes. The effect of a finite transducer bandwidth on the received PA signal was also examined. The simulation results suggest that the dominant frequency of the PA signals from non-aggregated RBCs decreases towards clinical frequency ranges as the aggregate size increases. The experimentally measured mean spectral power increased by ~6 dB for the largest aggregate compared to the non-aggregated samples. Such results confirm the theoretical predictions and illustrate the potential of using PA imaging for detecting RBC aggregation.

Effects of increased plasma viscosity and red blood cell aggregation on blood viscosity in vivo

1981 ◽  
Vol 241 (4) ◽  
pp. H513-H518 ◽  
Author(s):  
L. Gustafsson ◽  
L. Appelgren ◽  
H. E. Myrvold
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Apparent Viscosity ◽  
Cell Aggregation ◽  
Plasma Viscosity ◽  
Pressure Flow ◽  
Red Blood Cell Aggregation ◽  
Rbc Aggregation

The effects of increased plasma viscosity and induced red blood cell (RBC) aggregation on apparent viscosity of blood in vivo in the skeletal muscle of the dog were studied. Apparent viscosity in vivo was determined in the isolated and vasodilated calf muscles of one hindlimb by comparing pressure-flow relationships for RBC suspensions with pressure-flow relationships for a Newtonian solution of known viscosity. RBC suspensions of increased plasma viscosity with and without RBC aggregation were obtained by substituting plasma with isoviscous solutions of high- and low-molecular-weight dextran in saline. Hematocrits of the suspensions were adjusted to either 45 or 60%. The viscosities of the suspensions in vitro were determined in a Wells-Brookfield viscometer. Apparent viscosity of blood in vivo was found to be mainly dependent on the viscosity of plasma. RBC aggregation had no significant influence on the viscosity in vivo.

Nitric oxide generation by endothelial cells exposed to shear stress in glass tubes perfused with red blood cell suspensions: role of aggregation

2008 ◽  
Vol 294 (5) ◽  
pp. H2098-H2105 ◽  
Author(s):  
Ozlem Yalcin ◽  
Pinar Ulker ◽  
Ugur Yavuzer ◽  
Herbert J. Meiselman ◽  
Oguz K. Baskurt
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Vessel Wall ◽  
Plasma Viscosity ◽  
Autologous Plasma ◽  
Rbc Aggregation

Endothelial function is modulated by wall shear stress acting on the vessel wall, which is determined by fluid velocity and the local viscosity near the vessel wall. Red blood cell (RBC) aggregation may affect the local viscosity by favoring axial migration. The aim of this study was to investigate the role of RBC aggregation, with or without altered plasma viscosity, in the mechanically induced nitric oxide (NO)-related mechanisms of endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultured on the inner surface of cylindrical glass capillaries that were perfused with RBC suspensions having normal and increased aggregation at a nominal shear stress of 15 dyn/cm2. RBC aggregation was enhanced by two different approaches: 1) poloxamer-coated RBC suspended in normal, autologous plasma, resulting in enhanced aggregation but unchanged plasma viscosity and 2) normal RBC suspended in autologous plasma containing 0.5% dextran (mol mass 500 kDa), with a similar level of RBC aggregation but higher plasma viscosity. Compared with normal cells in unmodified plasma, perfusion with suspensions of poloxamer-coated RBC in normal plasma resulted in decreased levels of NO metabolites and serine 1177 phosphorylation of endothelial nitric oxide synthase (eNOS). Perfusion with normal RBC in plasma containing dextran resulted in a NO level that remained elevated, whereas only a modest decrease of phosphorylated eNOS level was observed. The results of this study suggest that increases of RBC aggregation tendency affect endothelial cell functions by altering local blood composition, especially if the alterations of RBC aggregation are due to modified cellular properties and not to plasma composition changes.

scholarly journals Photoacoustic Detection of Red Blood Cell Aggregation

2021 ◽  
Author(s):  
Eno Hysi
Keyword(s):  
Blood Cell ◽  
Oxygen Saturation ◽  
Red Blood Cell ◽  
Photoacoustic Imaging ◽  
Power Spectra ◽  
Aggregate Size ◽  
Cell Aggregation ◽  
Spectral Slope ◽  
Photoacoustic Detection ◽  
Rbc Aggregation

The potential of photoacoustic imaging for detecting red blood cell (RBC) aggregation is explored. Enhanced aggregation is observed in disorders such as diabetes impairing oxygen release into tissue. Simultaneous measurements of aggregation and oxygenation levels cannot be made using current tools. Photoacoustic detection of aggregation and assessment of oxygen saturation was investigated. A theoretical and experimental model of aggregation was developed using human and porcine RBCs. Frequency-domain analysis of the PA signals was used to derive the spectral slope and midband fit of the normalized power spectra for various hematorit and aggregation conditions. Oxygen saturation was assessed using multiple wavelengths of illumination. The experimental spectral slope (~0.3 dB/MHz) for non-aggregated samples agreed with the theory decreasing with increasing aggregate size. The midband fit increased by ~5 dB when the aggregate size reached the largest level while the oxygen saturation increased by > 20%. These results suggest that photoacoustic-radio-frequency-spectroscopic-parameters have the potential to monitor RBC aggregation and oxygenation level.

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