Autoregulation and mechanotransduction control the arteriolar response to small changes in hematocrit

Sriram, Krishna; Vázquez, Beatriz Y. Salazar; Tsai, Amy G.; Cabrales, Pedro; Intaglietta, Marcos; Tartakovsky, Daniel M.

doi:10.1152/ajpheart.00438.2012

Cited by 33 publications

(17 citation statements)

References 58 publications

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“…The predicted values of [NO] are within 5% of the experimental observations reported in (47). This figure provides a quantitative justification for the assumption of a linear relationship between [NO] and τ , which is routinely used in microcirculation models (see, e.g., (67) and the references therein). While this relationship is clearly nonlinear, it can Figure 4: (A) Predicted (line) and observed (symbols) dependence of NO production rate on WSS.…”

Section: Model Validationsupporting

confidence: 78%

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Shear-Induced Nitric Oxide Production by Endothelial Cells

Sriram

Laughlin

Rangamani

et al. 2016

Biophysical Journal

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We present a biochemical model of the wall shear stress-induced activation of endothelial nitric oxide synthase (eNOS) in an endothelial cell. The model includes three key mechanotransducers: mechanosensing ion channels, integrins, and G protein-coupled receptors. The reaction cascade consists of two interconnected parts. The first is rapid activation of calcium, which results in formation of calcium-calmodulin complexes, followed by recruitment of eNOS from caveolae. The second is phosphorylation of eNOS by protein kinases PKC and AKT. The model also includes a negative feedback loop due to inhibition of calcium influx into the cell by cyclic guanosine monophosphate (cGMP). In this feedback, increased nitric oxide (NO) levels cause an increase in cGMP levels, so that cGMP inhibition of calcium influx can limit NO production. The model was used to predict the dynamics of NO production by an endothelial cell subjected to a step increase of wall shear stress from zero to a finite physiologically relevant value. Among several experimentally observed features, the model predicts a highly nonlinear, biphasic transient behavior of eNOS activation and NO production: a rapid initial activation due to the very rapid influx of calcium into the cytosol (occurring within 1-5 min) is followed by a sustained period of activation due to protein kinases.

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Section: Model Validationsupporting

confidence: 78%

“…Concentrations of both NO and cGMP increase with WSS. Over a broad range of WSS this increase is highly non-linear, but within the physiologically relevant ranges of WSS (around 20 dynes/cm 2 ) one can use a linear relation between [NO] and WSS(47,49,67).…”

mentioning

confidence: 99%

Shear-Induced Nitric Oxide Production by Endothelial Cells

Sriram

Laughlin

Rangamani

et al. 2016

Biophysical Journal

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“…In a recent study by Sriram and co-workers (Sriram et al, 2012), the regulatory response of arterioles to small changes in hematocrit was predicted by using a two-phase fluid model. The relation between systemic hematocrit and CFL width was utilized for their simulation to predict changes in the NO transport and autoregulatory response.…”

Section: Resultsmentioning

confidence: 99%

Two-phase model for prediction of cell-free layer width in blood flow

Namgung

Cabrales

et al. 2013

Microvascular Research

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This study aimed to develop a numerical model capable of predicting changes in the cell-free layer (CFL) width in narrow tubes with consideration of red blood cell aggregation effects. The model development integrates to empirical relations for relative viscosity (ratio of apparent viscosity to medium viscosity) and core viscosity measured on independent blood samples to create a continuum model that includes these two regions. The constitutive relations were derived from in vitro experiments performed with three different glass-capillary tubes (inner diameter = 30, 50 and 100 μm) over a wide range of pseudoshear rates (5-300 s−1). The aggregation tendency of the blood samples was also varied by adding Dextran 500 kDa. Our model predicted that the CFL width was strongly modulated by the relative viscosity function. Aggregation increased the width of CFL, and this effect became more pronounced at low shear rates. The CFL widths predicted in the present study at high shear conditions were in agreement with those reported in previous studies. However, unlike previous multi-particle models, our model did not require a high computing cost, and it was capable of reproducing results for a thicker CFL width at low shear conditions, depending on aggregating tendency of the blood.

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“…may also contribute to the endothelial protective effect. On the other hand, it has been reported that there is a potential relationship between hematocrit and vascular function (Sriram et al, 2012).…”

Section: Discussionmentioning

confidence: 99%