TY - JOUR
T1 - Microvascular oxidative stress preceding leukocyte activation elicited by in vivo nitric oxide suppression
AU - Suematsu, M.
AU - Tamatani, T.
AU - Delano, F. A.
AU - Miyasaka, M.
AU - Forrest, M.
AU - Suzuki, H.
AU - Schmid-Schonbein, G. W.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1994
Y1 - 1994
N2 - This study was aimed to determine the mechanism by which endogenous nitric oxide suppression promotes leukocyte adhesion in vivo. The rat mesenteric microcirculation was superfused with N(G)-nitro-L-arginine methyl ester (L- NAME; 100 μM), and intracellular oxidant formation in several microcirculatory cellular components such as arteriolar and venular endothelium and mast cells was visually monitored by digital microfluorography assisted by carboxydichlorofluorescein (CDCF), a hydroperoxide-sensitive fluorogenic probe. Adherent leukocyte density was measured simultaneously. L-NAME induced a significant time-dependent increase in CDCF fluorescence in arteriolar and venular endothelium and mast cells followed by firm adhesion of leukocytes. L-NAME-induced CDCF elevation showed a different spatial distribution compared with that evoked by N- formylmethionyl-leucyl-phenylalanine, in which only local venular segments with adhering leukocytes exhibited CDCF fluorescence enhancement. The level of hydroperoxide formation in arterioles and venules evoked by 60-min L-NAME superfusion was equivalent to that induced by the superfusion of ~880 μM tert-butyl hydroperoxide for 10 min. Pretreatment with anti-intracellular adhesion molecule-1, anti-P-selectin, or anti-CD18 monoclonal antibody attenuated L-NAME-elicited venular leukocyte adhesion without abolishing CDCF fluorescence in situ. Pretreatment with desferioxamine (50 mg/kg iv; 1 h before L-NAME superfusion) significantly diminished the iron-catalyzed hydroperoxide formation in arterioles and venules, but not in interstitial mast cells, as well as subsequent venular leukocyte adhesion. These findings indicate that endogenous nitric oxide may modulate oxidative stress in mast cells, arteriolar and venular microvascular endothelium and thereby can play a crucial role in leukocyte recruitment in venules.
AB - This study was aimed to determine the mechanism by which endogenous nitric oxide suppression promotes leukocyte adhesion in vivo. The rat mesenteric microcirculation was superfused with N(G)-nitro-L-arginine methyl ester (L- NAME; 100 μM), and intracellular oxidant formation in several microcirculatory cellular components such as arteriolar and venular endothelium and mast cells was visually monitored by digital microfluorography assisted by carboxydichlorofluorescein (CDCF), a hydroperoxide-sensitive fluorogenic probe. Adherent leukocyte density was measured simultaneously. L-NAME induced a significant time-dependent increase in CDCF fluorescence in arteriolar and venular endothelium and mast cells followed by firm adhesion of leukocytes. L-NAME-induced CDCF elevation showed a different spatial distribution compared with that evoked by N- formylmethionyl-leucyl-phenylalanine, in which only local venular segments with adhering leukocytes exhibited CDCF fluorescence enhancement. The level of hydroperoxide formation in arterioles and venules evoked by 60-min L-NAME superfusion was equivalent to that induced by the superfusion of ~880 μM tert-butyl hydroperoxide for 10 min. Pretreatment with anti-intracellular adhesion molecule-1, anti-P-selectin, or anti-CD18 monoclonal antibody attenuated L-NAME-elicited venular leukocyte adhesion without abolishing CDCF fluorescence in situ. Pretreatment with desferioxamine (50 mg/kg iv; 1 h before L-NAME superfusion) significantly diminished the iron-catalyzed hydroperoxide formation in arterioles and venules, but not in interstitial mast cells, as well as subsequent venular leukocyte adhesion. These findings indicate that endogenous nitric oxide may modulate oxidative stress in mast cells, arteriolar and venular microvascular endothelium and thereby can play a crucial role in leukocyte recruitment in venules.
KW - P-selectin
KW - endothelium-leukocyte interaction
KW - intracellular adhesion molecule-1
KW - iron
KW - mast cells
KW - oxygen free radicals
UR - http://www.scopus.com/inward/record.url?scp=0028001936&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028001936&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.1994.266.6.h2410
DO - 10.1152/ajpheart.1994.266.6.h2410
M3 - Article
C2 - 8024002
AN - SCOPUS:0028001936
VL - 266
SP - H2410-H2415
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 6 35-6
ER -