Limits...
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.

Show MeSH

Related in: MedlinePlus

Concentration distribution under combination of endothelial oxidative stress and activation of leukocytes (Case 3).The NO, O2•− and peroxynitrite concentration distribution are shown for the entire arteriolar geometry in Panels A, C, and E, respectively and across the 200–300 µm region in Panels B, D and F, 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•−.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3375306&req=5

pone-0038912-g007: Concentration distribution under combination of endothelial oxidative stress and activation of leukocytes (Case 3).The NO, O2•− and peroxynitrite concentration distribution are shown for the entire arteriolar geometry in Panels A, C, and E, respectively and across the 200–300 µm region in Panels B, D and F, 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•−.

Mentions: For the combination of the endothelial oxidative stress condition with the activation of leukocytes (Case 3), the NO, O2•− and peroxynitrite concentration distribution are shown in Figure 7. Compared to the Case 2, the maximum NO concentration decreased at all regions of the blood vessel excluding PT region (remained unchanged in PT region) and the leukocytes. The concentration range of NO, O2•− and peroxynitrite within the leukocytes were 78−216 nM, 7000−14000 pM and 23−53 nM, respectively. In comparison to the Case 2, the maximum NO concentration changed by 0.9 fold, whereas the maximum O2•− and peroxynitrite concentrations increased by 14 and 8 fold, respectively. In comparison to the Case 2, the maximum NO concentration changed by 0.9 fold, the maximum O2•− concentration increased by 267, 5, 3 and 2 fold, and the maximum peroxynitrite concentration increased by 9, 7, 7 and 6 fold in the CR, CF, E and SM regions, respectively.


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

Kar S, Kavdia M - PLoS ONE (2012)

Concentration distribution under combination of endothelial oxidative stress and activation of leukocytes (Case 3).The NO, O2•− and peroxynitrite concentration distribution are shown for the entire arteriolar geometry in Panels A, C, and E, respectively and across the 200–300 µm region in Panels B, D and F, 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•−.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038912-g007: Concentration distribution under combination of endothelial oxidative stress and activation of leukocytes (Case 3).The NO, O2•− and peroxynitrite concentration distribution are shown for the entire arteriolar geometry in Panels A, C, and E, respectively and across the 200–300 µm region in Panels B, D and F, 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•−.
Mentions: For the combination of the endothelial oxidative stress condition with the activation of leukocytes (Case 3), the NO, O2•− and peroxynitrite concentration distribution are shown in Figure 7. Compared to the Case 2, the maximum NO concentration decreased at all regions of the blood vessel excluding PT region (remained unchanged in PT region) and the leukocytes. The concentration range of NO, O2•− and peroxynitrite within the leukocytes were 78−216 nM, 7000−14000 pM and 23−53 nM, respectively. In comparison to the Case 2, the maximum NO concentration changed by 0.9 fold, whereas the maximum O2•− and peroxynitrite concentrations increased by 14 and 8 fold, respectively. In comparison to the Case 2, the maximum NO concentration changed by 0.9 fold, the maximum O2•− concentration increased by 267, 5, 3 and 2 fold, and the maximum peroxynitrite concentration increased by 9, 7, 7 and 6 fold in the CR, CF, E and SM regions, respectively.

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