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Local oxidative and nitrosative stress increases in the microcirculation during leukocytes-endothelial cell interactions.

Kar S, Kavdia M - PLoS ONE (2012)

Bottom Line: Endothelial dysfunction is characterized by increased superoxide (O(2) (•-)) production from endothelium and reduction in NO bioavailability.The results showed that the maximum concentrations of NO decreased ~0.6 fold, O(2)(•-) increased ~27 fold and peroxynitrite increased ~30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions.The results show that the onset of endothelial oxidative stress can cause an increase in O(2)(•-) and peroxynitrite concentration in the lumen.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, Michigan, United States of America. s.kar@wayne.edu

ABSTRACT
Leukocyte-endothelial cell interactions and leukocyte activation are important factors for vascular diseases including nephropathy, retinopathy and angiopathy. In addition, endothelial cell dysfunction is reported in vascular disease condition. Endothelial dysfunction is characterized by increased superoxide (O(2) (•-)) production from endothelium and reduction in NO bioavailability. Experimental studies have suggested a possible role for leukocyte-endothelial cell interaction in the vessel NO and peroxynitrite levels and their role in vascular disorders in the arterial side of microcirculation. However, anti-adhesion therapies for preventing leukocyte-endothelial cell interaction related vascular disorders showed limited success. The endothelial dysfunction related changes in vessel NO and peroxynitrite levels, leukocyte-endothelial cell interaction and leukocyte activation are not completely understood in vascular disorders. The objective of this study was to investigate the role of endothelial dysfunction extent, leukocyte-endothelial interaction, leukocyte activation and superoxide dismutase therapy on the transport and interactions of NO, O(2)(•-) and peroxynitrite in the microcirculation. We developed a biotransport model of NO, O(2)(•-) and peroxynitrite in the arteriolar microcirculation and incorporated leukocytes-endothelial cell interactions. The concentration profiles of NO, O(2)(•-) and peroxynitrite within blood vessel and leukocytes are presented at multiple levels of endothelial oxidative stress with leukocyte activation and increased superoxide dismutase accounted for in certain cases. The results showed that the maximum concentrations of NO decreased ~0.6 fold, O(2)(•-) increased ~27 fold and peroxynitrite increased ~30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions. The results show that the onset of endothelial oxidative stress can cause an increase in O(2)(•-) and peroxynitrite concentration in the lumen. The increased O(2) (•-) and peroxynitrite can cause leukocytes priming through peroxynitrite and leukocytes activation through secondary stimuli of O(2)(•-) in bloodstream without endothelial interaction. This finding supports that leukocyte rolling/adhesion and activation are independent events.

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Related in: MedlinePlus

Concentration distribution under normal physiological conditions (Case 1).Panel A, C and E shows the NO, O2•− and peroxynitrite (referred as CPer) concentration distribution, respectively across the entire arteriolar geometry. Panel B,D and F shows the NO, O2•− and peroxynitrite concentration distribution, respectively across a segment of the arteriolar geometry between 200 and 300 µm encompassing the luminal, E, SM and NPT regions. The endothelial and capillary based O2•− production rates in this case were 5% of their respective NO production rates and the leukocytes were considered inactive.
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pone-0038912-g003: Concentration distribution under normal physiological conditions (Case 1).Panel A, C and E shows the NO, O2•− and peroxynitrite (referred as CPer) concentration distribution, respectively across the entire arteriolar geometry. Panel B,D and F shows the NO, O2•− and peroxynitrite concentration distribution, respectively across a segment of the arteriolar geometry between 200 and 300 µm encompassing the luminal, E, SM and NPT regions. The endothelial and capillary based O2•− production rates in this case were 5% of their respective NO production rates and the leukocytes were considered inactive.

Mentions: The NO, O2•− and peroxynitrite concentrations are shown in Figure 3A, C and E, respectively for the entire vessel and in Figure 3B, D and F, respectively for a segment of the vessel between 200 and 300 µm encompassing the luminal, endothelial (E), smooth muscle (SM) and non-perfused parenchymal tissue (NPT) region. The concentration range of NO, O2•− and peroxynitrite within the leukocytes were 88−248 nM, 0.2−200 pM, and 1−2 nM, respectively. The concentration range of NO, O2•− and peroxynitrite at other regions of the arteriole are shown in Table 5. The radial concentration profiles for NO, O2•− and peroxynitrite at location P1 and P2 are shown in Figure 4 A and B, respectively and their maximum values at the endothelium are shown in Table 4.


Local oxidative and nitrosative stress increases in the microcirculation during leukocytes-endothelial cell interactions.

Kar S, Kavdia M - PLoS ONE (2012)

Concentration distribution under normal physiological conditions (Case 1).Panel A, C and E shows the NO, O2•− and peroxynitrite (referred as CPer) concentration distribution, respectively across the entire arteriolar geometry. Panel B,D and F shows the NO, O2•− and peroxynitrite concentration distribution, respectively across a segment of the arteriolar geometry between 200 and 300 µm encompassing the luminal, E, SM and NPT regions. The endothelial and capillary based O2•− production rates in this case were 5% of their respective NO production rates and the leukocytes were considered inactive.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375306&req=5

pone-0038912-g003: Concentration distribution under normal physiological conditions (Case 1).Panel A, C and E shows the NO, O2•− and peroxynitrite (referred as CPer) concentration distribution, respectively across the entire arteriolar geometry. Panel B,D and F shows the NO, O2•− and peroxynitrite concentration distribution, respectively across a segment of the arteriolar geometry between 200 and 300 µm encompassing the luminal, E, SM and NPT regions. The endothelial and capillary based O2•− production rates in this case were 5% of their respective NO production rates and the leukocytes were considered inactive.
Mentions: The NO, O2•− and peroxynitrite concentrations are shown in Figure 3A, C and E, respectively for the entire vessel and in Figure 3B, D and F, respectively for a segment of the vessel between 200 and 300 µm encompassing the luminal, endothelial (E), smooth muscle (SM) and non-perfused parenchymal tissue (NPT) region. The concentration range of NO, O2•− and peroxynitrite within the leukocytes were 88−248 nM, 0.2−200 pM, and 1−2 nM, respectively. The concentration range of NO, O2•− and peroxynitrite at other regions of the arteriole are shown in Table 5. The radial concentration profiles for NO, O2•− and peroxynitrite at location P1 and P2 are shown in Figure 4 A and B, respectively and their maximum values at the endothelium are shown in Table 4.

Bottom Line: Endothelial dysfunction is characterized by increased superoxide (O(2) (•-)) production from endothelium and reduction in NO bioavailability.The results showed that the maximum concentrations of NO decreased ~0.6 fold, O(2)(•-) increased ~27 fold and peroxynitrite increased ~30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions.The results show that the onset of endothelial oxidative stress can cause an increase in O(2)(•-) and peroxynitrite concentration in the lumen.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, Michigan, United States of America. s.kar@wayne.edu

ABSTRACT
Leukocyte-endothelial cell interactions and leukocyte activation are important factors for vascular diseases including nephropathy, retinopathy and angiopathy. In addition, endothelial cell dysfunction is reported in vascular disease condition. Endothelial dysfunction is characterized by increased superoxide (O(2) (•-)) production from endothelium and reduction in NO bioavailability. Experimental studies have suggested a possible role for leukocyte-endothelial cell interaction in the vessel NO and peroxynitrite levels and their role in vascular disorders in the arterial side of microcirculation. However, anti-adhesion therapies for preventing leukocyte-endothelial cell interaction related vascular disorders showed limited success. The endothelial dysfunction related changes in vessel NO and peroxynitrite levels, leukocyte-endothelial cell interaction and leukocyte activation are not completely understood in vascular disorders. The objective of this study was to investigate the role of endothelial dysfunction extent, leukocyte-endothelial interaction, leukocyte activation and superoxide dismutase therapy on the transport and interactions of NO, O(2)(•-) and peroxynitrite in the microcirculation. We developed a biotransport model of NO, O(2)(•-) and peroxynitrite in the arteriolar microcirculation and incorporated leukocytes-endothelial cell interactions. The concentration profiles of NO, O(2)(•-) and peroxynitrite within blood vessel and leukocytes are presented at multiple levels of endothelial oxidative stress with leukocyte activation and increased superoxide dismutase accounted for in certain cases. The results showed that the maximum concentrations of NO decreased ~0.6 fold, O(2)(•-) increased ~27 fold and peroxynitrite increased ~30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions. The results show that the onset of endothelial oxidative stress can cause an increase in O(2)(•-) and peroxynitrite concentration in the lumen. The increased O(2) (•-) and peroxynitrite can cause leukocytes priming through peroxynitrite and leukocytes activation through secondary stimuli of O(2)(•-) in bloodstream without endothelial interaction. This finding supports that leukocyte rolling/adhesion and activation are independent events.

Show MeSH
Related in: MedlinePlus