The Experts below are selected from a list of 252 Experts worldwide ranked by ideXlab platform
Karel Tyml - One of the best experts on this subject based on the ideXlab platform.
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ascorbate inhibits reduced arteriolar conducted vasoconstriction in septic mouse Cremaster Muscle
Microcirculation, 2007Co-Authors: Rebecca L Mckinnon, Darcy Lidington, Karel TymlAbstract:Objective: The mechanism of neuronal nitric oxide synthase (nNOS)-dependent reduction in arteriolar conducted vasoconstriction in sepsis, and the possible protection by antioxidants, are unknown. The authors hypothesized that ascorbate inhibits the conduction deficit by reducing nNOS-derived NO production.Methods: Using intravital microscopy and the cecal ligation and perforation (CLP) model of sepsis (24 h), arterioles in the Cremaster Muscle of male C57BL/6 wild-type mice were locally stimulated with KCl to initiate conducted vasoconstriction. The authors used the ratio of conducted constriction (500 μ m upstream) to local constriction as an index of conduction (CR500). Cremaster Muscle NOS enzymatic activity and protein expression, and plasma nitrite/nitrate levels were determined in control and septic mice. Intravenous ascorbate bolus (200 mg/kg in 0.1 ml of saline) was given early (0 h) or delayed at 23 h post CLP.Results: Sepsis reduced CR500 from 0.73 ± 0.03 to 0.21 ± 0.03, increased nNOS activity ...
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reduced arteriolar conducted vasoconstriction in septic mouse Cremaster Muscle is mediated by nnos derived no
Cardiovascular Research, 2006Co-Authors: Rebecca L Mckinnon, Darcy Lidington, Michael L Bolon, Yves Ouellette, Gerald M Kidder, Karel TymlAbstract:Objective: Increased nitric oxide (NO) production in sepsis precipitates microcirculatory dysfunction. We aimed (i) to determine if NO is the key water-soluble factor in the recently discovered sepsis-induced deficit in arteriolar conducted vasoconstriction, (ii) to identify which nitric oxide synthase (NOS) isoforms account for this deficit, and (iii) to examine the potential role of connexin37 (Cx37, a hypothesized signaling target of NO) in arteriolar conduction. Methods: Using intravital microscopy and the cecal ligation and perforation 24-h model of sepsis, arterioles in the Cremaster Muscle of male C57BL/6 wild-type (WT), iNOS−/−, eNOS−/−, nNOS−/− and Cx37−/− mice were locally stimulated with KCl to initiate conducted vasoconstriction. We used the ratio of conducted constriction (500 μm upstream) to local constriction as an index of conduction (CR500). NOS enzymatic activity and protein expression were determined in control and septic Cremaster Muscles. Results: Sepsis reduced CR500 in WT mice [from 0.77 ± 0.05 to 0.20 ± 0.02 (means ± SE) independent of the site of stimulation along the arteriole], in iNOS−/− and eNOS−/− mice, but not in nNOS−/− mice. The nNOS inhibitor 7-nitroindazole or NO scavenger HbO2 restored CR500 in septic WT mice, but blockade of soluble guanylate cyclase had no effect. Sepsis increased cNOS (eNOS+nNOS) activity in WT mice (from 340 ± 40 to 490 ± 30 pmol/mg/h) and in eNOS−/−, but not in nNOS−/− mice (iNOS activity was negligible in all mice). Sepsis did not alter nNOS protein expression in WT mice. CR500 in non-septic Cx37−/− mice (0.15 ± 0.1) was similar to that observed in septic WT mice. Conclusion: Increased nNOS activity and the resultant increased NO production in the septic mouse Cremaster Muscle are the key factors responsible for the deficit in conducted vasoconstriction along the arteriole. Deletion of Cx37 results in reduced CR500, which is consistent with the hypothesis that Cx37 in the arteriole could be a target of NO signaling.
Rebecca L Mckinnon - One of the best experts on this subject based on the ideXlab platform.
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ascorbate inhibits reduced arteriolar conducted vasoconstriction in septic mouse Cremaster Muscle
Microcirculation, 2007Co-Authors: Rebecca L Mckinnon, Darcy Lidington, Karel TymlAbstract:Objective: The mechanism of neuronal nitric oxide synthase (nNOS)-dependent reduction in arteriolar conducted vasoconstriction in sepsis, and the possible protection by antioxidants, are unknown. The authors hypothesized that ascorbate inhibits the conduction deficit by reducing nNOS-derived NO production.Methods: Using intravital microscopy and the cecal ligation and perforation (CLP) model of sepsis (24 h), arterioles in the Cremaster Muscle of male C57BL/6 wild-type mice were locally stimulated with KCl to initiate conducted vasoconstriction. The authors used the ratio of conducted constriction (500 μ m upstream) to local constriction as an index of conduction (CR500). Cremaster Muscle NOS enzymatic activity and protein expression, and plasma nitrite/nitrate levels were determined in control and septic mice. Intravenous ascorbate bolus (200 mg/kg in 0.1 ml of saline) was given early (0 h) or delayed at 23 h post CLP.Results: Sepsis reduced CR500 from 0.73 ± 0.03 to 0.21 ± 0.03, increased nNOS activity ...
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reduced arteriolar conducted vasoconstriction in septic mouse Cremaster Muscle is mediated by nnos derived no
Cardiovascular Research, 2006Co-Authors: Rebecca L Mckinnon, Darcy Lidington, Michael L Bolon, Yves Ouellette, Gerald M Kidder, Karel TymlAbstract:Objective: Increased nitric oxide (NO) production in sepsis precipitates microcirculatory dysfunction. We aimed (i) to determine if NO is the key water-soluble factor in the recently discovered sepsis-induced deficit in arteriolar conducted vasoconstriction, (ii) to identify which nitric oxide synthase (NOS) isoforms account for this deficit, and (iii) to examine the potential role of connexin37 (Cx37, a hypothesized signaling target of NO) in arteriolar conduction. Methods: Using intravital microscopy and the cecal ligation and perforation 24-h model of sepsis, arterioles in the Cremaster Muscle of male C57BL/6 wild-type (WT), iNOS−/−, eNOS−/−, nNOS−/− and Cx37−/− mice were locally stimulated with KCl to initiate conducted vasoconstriction. We used the ratio of conducted constriction (500 μm upstream) to local constriction as an index of conduction (CR500). NOS enzymatic activity and protein expression were determined in control and septic Cremaster Muscles. Results: Sepsis reduced CR500 in WT mice [from 0.77 ± 0.05 to 0.20 ± 0.02 (means ± SE) independent of the site of stimulation along the arteriole], in iNOS−/− and eNOS−/− mice, but not in nNOS−/− mice. The nNOS inhibitor 7-nitroindazole or NO scavenger HbO2 restored CR500 in septic WT mice, but blockade of soluble guanylate cyclase had no effect. Sepsis increased cNOS (eNOS+nNOS) activity in WT mice (from 340 ± 40 to 490 ± 30 pmol/mg/h) and in eNOS−/−, but not in nNOS−/− mice (iNOS activity was negligible in all mice). Sepsis did not alter nNOS protein expression in WT mice. CR500 in non-septic Cx37−/− mice (0.15 ± 0.1) was similar to that observed in septic WT mice. Conclusion: Increased nNOS activity and the resultant increased NO production in the septic mouse Cremaster Muscle are the key factors responsible for the deficit in conducted vasoconstriction along the arteriole. Deletion of Cx37 results in reduced CR500, which is consistent with the hypothesis that Cx37 in the arteriole could be a target of NO signaling.
Darcy Lidington - One of the best experts on this subject based on the ideXlab platform.
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ascorbate inhibits reduced arteriolar conducted vasoconstriction in septic mouse Cremaster Muscle
Microcirculation, 2007Co-Authors: Rebecca L Mckinnon, Darcy Lidington, Karel TymlAbstract:Objective: The mechanism of neuronal nitric oxide synthase (nNOS)-dependent reduction in arteriolar conducted vasoconstriction in sepsis, and the possible protection by antioxidants, are unknown. The authors hypothesized that ascorbate inhibits the conduction deficit by reducing nNOS-derived NO production.Methods: Using intravital microscopy and the cecal ligation and perforation (CLP) model of sepsis (24 h), arterioles in the Cremaster Muscle of male C57BL/6 wild-type mice were locally stimulated with KCl to initiate conducted vasoconstriction. The authors used the ratio of conducted constriction (500 μ m upstream) to local constriction as an index of conduction (CR500). Cremaster Muscle NOS enzymatic activity and protein expression, and plasma nitrite/nitrate levels were determined in control and septic mice. Intravenous ascorbate bolus (200 mg/kg in 0.1 ml of saline) was given early (0 h) or delayed at 23 h post CLP.Results: Sepsis reduced CR500 from 0.73 ± 0.03 to 0.21 ± 0.03, increased nNOS activity ...
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reduced arteriolar conducted vasoconstriction in septic mouse Cremaster Muscle is mediated by nnos derived no
Cardiovascular Research, 2006Co-Authors: Rebecca L Mckinnon, Darcy Lidington, Michael L Bolon, Yves Ouellette, Gerald M Kidder, Karel TymlAbstract:Objective: Increased nitric oxide (NO) production in sepsis precipitates microcirculatory dysfunction. We aimed (i) to determine if NO is the key water-soluble factor in the recently discovered sepsis-induced deficit in arteriolar conducted vasoconstriction, (ii) to identify which nitric oxide synthase (NOS) isoforms account for this deficit, and (iii) to examine the potential role of connexin37 (Cx37, a hypothesized signaling target of NO) in arteriolar conduction. Methods: Using intravital microscopy and the cecal ligation and perforation 24-h model of sepsis, arterioles in the Cremaster Muscle of male C57BL/6 wild-type (WT), iNOS−/−, eNOS−/−, nNOS−/− and Cx37−/− mice were locally stimulated with KCl to initiate conducted vasoconstriction. We used the ratio of conducted constriction (500 μm upstream) to local constriction as an index of conduction (CR500). NOS enzymatic activity and protein expression were determined in control and septic Cremaster Muscles. Results: Sepsis reduced CR500 in WT mice [from 0.77 ± 0.05 to 0.20 ± 0.02 (means ± SE) independent of the site of stimulation along the arteriole], in iNOS−/− and eNOS−/− mice, but not in nNOS−/− mice. The nNOS inhibitor 7-nitroindazole or NO scavenger HbO2 restored CR500 in septic WT mice, but blockade of soluble guanylate cyclase had no effect. Sepsis increased cNOS (eNOS+nNOS) activity in WT mice (from 340 ± 40 to 490 ± 30 pmol/mg/h) and in eNOS−/−, but not in nNOS−/− mice (iNOS activity was negligible in all mice). Sepsis did not alter nNOS protein expression in WT mice. CR500 in non-septic Cx37−/− mice (0.15 ± 0.1) was similar to that observed in septic WT mice. Conclusion: Increased nNOS activity and the resultant increased NO production in the septic mouse Cremaster Muscle are the key factors responsible for the deficit in conducted vasoconstriction along the arteriole. Deletion of Cx37 results in reduced CR500, which is consistent with the hypothesis that Cx37 in the arteriole could be a target of NO signaling.
Unsu Jung - One of the best experts on this subject based on the ideXlab platform.
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regulation of e selectin p selectin and intercellular adhesion molecule 1 expression in mouse Cremaster Muscle vasculature
Microcirculation, 1997Co-Authors: Unsu JungAbstract:Objective: To investigate the expression of P- and E-selectin and intercellular adhesion molecule 1 (ICAM-1) in the vasculature of mouse Cremaster Muscles both with and without tumor necrosis factor a (TNF-α) treatment.Methods: Mice received injections of monoclonal antibody to P-selectin, E-selectin, or ICAM-1 before fixation to restrict detection to antigen expressed on the endothelial surface. Whole-mount preparations of mouse Cremaster Muscles were fixed in acetone and stained using biotinylated secondary antibody and peroxidase-conjugated streptavidin.Results: P-selectin is expressed on the endothelial surface of Cremaster Muscle venules within 10 minutes after exteriorization. Expression increases upon treatment with TNF-α (2 hours), reflecting transcriptional regulation of P-selectin expression in situ. The baseline E-selectin expression is patchy and barely detectable but shows a significant upregulation after treatment with TNF-α. ICAM-1 is constitutively expressed in unstimulated mouse Cremaster...
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Regulation of E-selectin, P-selectin, and intercellular adhesion molecule 1 expression in mouse Cremaster Muscle vasculature
Microcirculation, 1997Co-Authors: Unsu Jung, Klaus LeyAbstract:OBJECTIVE: To investigate the expression of P- and E-selectin and intercellular adhesion molecule 1 (ICAM-1) in the vasculature of mouse Cremaster Muscles both with and without tumor necrosis factor alpha (TNF-alpha) treatment. METHODS: Mice received injections of monoclonal antibody to P-selectin, E-selectin, or ICAM-1 before fixation to restrict detection to antigen expressed on the endothelial surface. Whole-mount preparations of mouse Cremaster Muscles were fixed in acetone and stained using biotinylated secondary antibody and peroxidase-conjugated streptavidin. RESULTS: P-selectin is expressed on the endothelial surface of Cremaster Muscle venules within 10 minutes after exteriorization. Expression increases upon treatment with TNF-alpha (2 hours), reflecting transcriptional regulation of P-selectin expression in situ. The baseline E-selectin expression is patchy and barely detectable but shows a significant upregulation after treatment with TNF-alpha. [CAM-1 is constitutively expressed in unstimulated mouse Cremaster venules and slightly upregulated after 2 hours of TNF-alpha treatment. Under baseline conditions, neither E-selectin, P-selectin, nor ICAM-1 is detectable in arterioles or capillaries. After TNF-alpha treatment, arterioles stain faintly for P-selectin, but not E-selectin or ICAM-1. CONCLUSION: The temporal and spatial pattern of expression of P- and E-selectin and ICAM-1 is consistent with the functional role of these molecules in mediating preferential leukocyte rolling and adhesion in mouse Cremaster Muscle venules
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velocity differences between l and p selectin dependent neutrophil rolling in venules of mouse Cremaster Muscle in vivo
American Journal of Physiology-heart and Circulatory Physiology, 1996Co-Authors: Unsu Jung, Daniel C Bullard, Thomas F TedderAbstract:After surgical trauma, leukocyte rolling is initially normal in L-selectin-deficient mice and reduced at later times, whereas leukocyte rolling is initially absent in P-selectin-deficient mice but induced later. Here, we examined the possibility that P- and L-selectin support rolling at different characteristic velocities using intravital microscopy of venules of the exteriorized Cremaster Muscle venules of wild type (WT) and P- and L-selectin-deficient mice. At > 50 min after exteriorization, rolling in P-selectin-deficient mice occurred at significantly higher velocities (129 +/- 89 microns/s) than in WT mice (49 +/- 23 microns/s). Rolling velocity distribution in L-selectin-deficient mice was similar to WT mice immediately after exteriorization. Histological examination of Giemsa-stained whole-mount preparations in Cremaster Muscle venules revealed that the majority of rolling cells (approximately 90% in all genotypes) were granulocytes. We conclude that P-selectin mediates leukocyte rolling at velocities < 50 microns/s, whereas L-selectin sustains more rapid rolling. Under physiological conditions, P- and L-selectin synergize to support rolling at velocities between 20 and 70 microns/s as seen in WT mice.
Gerald M Kidder - One of the best experts on this subject based on the ideXlab platform.
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reduced arteriolar conducted vasoconstriction in septic mouse Cremaster Muscle is mediated by nnos derived no
Cardiovascular Research, 2006Co-Authors: Rebecca L Mckinnon, Darcy Lidington, Michael L Bolon, Yves Ouellette, Gerald M Kidder, Karel TymlAbstract:Objective: Increased nitric oxide (NO) production in sepsis precipitates microcirculatory dysfunction. We aimed (i) to determine if NO is the key water-soluble factor in the recently discovered sepsis-induced deficit in arteriolar conducted vasoconstriction, (ii) to identify which nitric oxide synthase (NOS) isoforms account for this deficit, and (iii) to examine the potential role of connexin37 (Cx37, a hypothesized signaling target of NO) in arteriolar conduction. Methods: Using intravital microscopy and the cecal ligation and perforation 24-h model of sepsis, arterioles in the Cremaster Muscle of male C57BL/6 wild-type (WT), iNOS−/−, eNOS−/−, nNOS−/− and Cx37−/− mice were locally stimulated with KCl to initiate conducted vasoconstriction. We used the ratio of conducted constriction (500 μm upstream) to local constriction as an index of conduction (CR500). NOS enzymatic activity and protein expression were determined in control and septic Cremaster Muscles. Results: Sepsis reduced CR500 in WT mice [from 0.77 ± 0.05 to 0.20 ± 0.02 (means ± SE) independent of the site of stimulation along the arteriole], in iNOS−/− and eNOS−/− mice, but not in nNOS−/− mice. The nNOS inhibitor 7-nitroindazole or NO scavenger HbO2 restored CR500 in septic WT mice, but blockade of soluble guanylate cyclase had no effect. Sepsis increased cNOS (eNOS+nNOS) activity in WT mice (from 340 ± 40 to 490 ± 30 pmol/mg/h) and in eNOS−/−, but not in nNOS−/− mice (iNOS activity was negligible in all mice). Sepsis did not alter nNOS protein expression in WT mice. CR500 in non-septic Cx37−/− mice (0.15 ± 0.1) was similar to that observed in septic WT mice. Conclusion: Increased nNOS activity and the resultant increased NO production in the septic mouse Cremaster Muscle are the key factors responsible for the deficit in conducted vasoconstriction along the arteriole. Deletion of Cx37 results in reduced CR500, which is consistent with the hypothesis that Cx37 in the arteriole could be a target of NO signaling.