Geometrical description of the problem.

<p><b>Panel A</b> shows the schematic of the arteriolar geometry. The geometry consists of concentric cylinders representing the different regions of the arteriole. The different regions fall under the category of either luminal or abluminal region. The luminal and abluminal regions are separated by the endothelial region (E). The luminal region consists of the RBC rich core (CR) and RBC free plasma region (CF). The abluminal region consists of the interstitial region (IS), smooth muscle region (SM), non-perfused (NPT) and capillary perfused (PT) parenchymal regions. L1, L2 and L3 represent the leukocytes interacting with the endothelium. P_in and P_out represent the inlet and outlet of the arteriolar/vessel segment, respectively. P₁ and P₂ represent the locations where the radial concentration profiles of NO, O₂^•− and peroxynitrite were obtained and are located at distances of 230 and 345 µm, respectively from P_in. <b>Panel B</b> shows the schematic of finite element mesh grid with relative accuracy set to 0.001.</p

Schematic representation of the role of endothelial dysfunction on leukocyte related events through interactions between free radical species (NO, ROS and peroxynitrite).

<p>The free radical species are represented by the orange ovals, the leukocyte related events and endothelial dysfunction are represented by the yellow compartments and the chemical species expressed as a result of the interactions of free radicals (cytokines, adhesion molecules and inflammatory agents) are represented by the light green compartments. Endothelial dysfunction leads to increased ROS production from endothelium and a possible reduction in NO availability (indicated by the dashed lines). The ROS and NO combine to form peroynitrite (Per). ROS and peroxynitrite increase expression of adhesion molecules and cytokines leading to leukocyte recruitment and priming. Peroxynitrite and ROS can also prime and activate primed leukocytes, respectively. The dashed lines connecting the leukocyte related events shows the uncertaintly associated with their sequential nature.</p

Concentration distribution under conditions of endothelial oxidative stress (Case 2).

<p>The NO, O₂^•− and peroxynitrite concentration distribution are shown for the entire arteriolar geometry in <b>Panels A, C, and E</b>, respectively and across the 200–300 µm region in <b>Panels B, D and F</b>, respectively. The endothelial and capillary based O₂^•− production rates in this case were 20% of their respective NO production rates and the leukocytes were considered inactive.</p

Maximum endothelial concentrations of NO, O₂^•− and peroxynitrite at location P₁² and location P₂³. C_Per refers to the peroxynitrite concentration.

2<p>The location P₁ refers to a straight line passing through the leukocyte L2 at a distance of 230 µm from the vessel inlet P_in as seen in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038912#pone-0038912-g002" target="_blank">Figure 2</a>.</p>3<p>The location P₂ refers to a straight line passing the centers of leukocytes L2 and L3 at a distance of 345 µm from the vessel inlet P_in as seen in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038912#pone-0038912-g002" target="_blank">Figure 2</a>.</p

Concentration distribution under combination of endothelial oxidative stress and activation of leukocytes (Case 3).

<p>The NO, O₂^•− and peroxynitrite concentration distribution are shown for the entire arteriolar geometry in <b>Panels A, C, and E,</b> respectively and across the 200–300 µm region in <b>Panels B, D and F,</b> respectively. The O₂^•− production in the endothelium and capillary in this case were 20% of their respective NO production and the leukocytes were in activated state producing NO and O₂^•−.</p

Radial concentration profiles at locations P₁ and P₂ for the Case 4.

<p><b>Panel A</b> and <b>B</b> shows the radial concentration profiles of NO, O₂^•− and peroxynitrite at the location P₁ and P₂, respectively.</p

Radial concentration profiles at locations P₁ and P₂ for the Case 5.

<p><b>Panel A </b><b>and </b><b>B</b> shows the radial concentration profiles of NO, O₂^•− and peroxynitrite at the location P₁ and P₂, respectively.</p

Radial concentration profiles at locations P₁ and P₂ for the Case 1.

<p><b>Panel A</b> and <b>B</b> shows the radial concentration profiles of NO, O₂^•− and peroxynitrite at the location P₁ and P₂, respectively.</p

Endothelial, capillary and leukocyte based NO and O₂^•− production rates and SOD concentration for the different cases simulated.

1<p><b>P_i,L</b> refers to the production rate of NO and O₂^•− from the leukocytes L1, L2 and L3.</p

Concentration range of NO, O₂^•− and peroxynitrite at different regions of the arteriole geometry.

<p>Concentration range of NO, O₂^•− and peroxynitrite at different regions of the arteriole geometry.</p