From the Departments of Neurosurgery, Cell Biology and Physiology, and
Anatomy and Neurobiology, Washington University School of Medicine, and St
Louis Children's Hospital, St Louis, Mo.
Correspondence to Jeffrey M. Gidday, PhD, Department of Neurosurgery, Box 8057, Washington University School of Medicine, St Louis, MO 63110. E-mail gidday{at}kids.wustl.edu
Background and Purpose—Recent
studies indicate that leukocytes are important contributors to
secondary vascular and parenchymal injury after cerebral
ischemia. The present study was undertaken to define nitric
oxide (NO)-based mechanisms that regulate
leukocyte-endothelial interactions in the cerebral
vasculature, how these mechanisms are affected by cerebral
ischemia, and whether NO-based therapies can affect
postischemic leukocyte dynamics.
Methods—Leukocyte adherence to pial venules of
anesthetized newborn piglets was quantified by in situ
fluorescence videomicroscopy through closed cranial windows
during basal conditions and during reperfusion after 9 minutes of
asphyxia. Nitric oxide synthase (NOS) was inhibited by local window
superfusion of L-nitroarginine; superfusion of sodium
nitroprusside was used to donate NO.
Results—Local inhibition of NOS under resting conditions
increased leukocyte-endothelial adherence 2.2-fold and
3.9-fold over baseline values after 1 hour and 2 hours, respectively;
this response was completely blocked by cosuperfusion with
L-arginine. Cosuperfusion of superoxide dismutase reversed
L-nitroarginine-induced leukocyte adherence by 89% and
63% at these respective time points. The extent of acute leukocyte
adherence elicited by NOS inhibition was similar in magnitude to that
observed during the initial 2 hours of reperfusion after asphyxia.
Leukocyte adherence was not additionally increased in asphyxic animals
treated with L-nitroarginine. Sodium nitroprusside robustly
inhibited asphyxia-induced leukocyte adherence back to control
levels.
Conclusions—NO exerts a tonic antiadherent effect in the cerebral
microcirculation by inactivation of adherence-promoting superoxide
radical formation. Cerebral ischemia is associated with an
inhibition of NOS or lower levels of NO, which results in
leukocyte-endothelial adherence that can be prevented
by NO donors. The latter may be useful therapeutically to prevent the
purported vascular and parenchymal dysfunction and injury caused by
activated leukocytes in ischemic brain.
Guest Editors Safar Center for Resuscitation Research
Departments of Anesthesiology and Critical Care Medicine University
of Pittsburgh School of Medicine Pittsburgh, Pennsylvania
© 1998 American Heart Association, Inc.
Original Contributions
Modulation of Basal and Postischemic Leukocyte-Endothelial Adherence by Nitric Oxide
Editorial Comment
This article has been cited by other articles:
 |
|
 |
|
  V. Anttila, H. Christou, I. Hagino, Y. Iwata, B. A. Mettler, A. Fernandez-Gonzalez, D. Zurakowski, and R. A. Jonas Cerebral Endothelial Nitric Oxide Synthase Expression is Reduced After Very Low Flow Bypass Ann. Thorac. Surg., June 1, 2006; 81(6): 2202 - 2206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Drummond, L. D. McKay, D. J. Cole, and P. M. Patel The Role of Nitric Oxide Synthase Inhibition in the Adverse Effects of Etomidate in the Setting of Focal Cerebral Ischemia in Rats Anesth. Analg., March 1, 2005; 100(3): 841 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Gursoy-Ozdemir, A. Can, and T. Dalkara Reperfusion-Induced Oxidative/Nitrative Injury to Neurovascular Unit After Focal Cerebral Ischemia Stroke, June 1, 2004; 35(6): 1449 - 1453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Altay, E. R. Gonzales, T. S. Park, and J. M. Gidday Cerebrovascular inflammation after brief episodic hypoxia: modulation by neuronal and endothelial nitric oxide synthase J Appl Physiol, March 1, 2004; 96(3): 1223 - 1230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Belayev, E. Pinard, H. Nallet, J. Seylaz, Y. Liu, P. Riyamongkol, W. Zhao, R. Busto, and M. D. Ginsberg Albumin Therapy of Transient Focal Cerebral Ischemia: In Vivo Analysis of Dynamic Microvascular Responses Stroke, April 1, 2002; 33(4): 1077 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Koga, M. Ishibashi, I. Ueki, S. Yatsuga, R. Fukiyama, Y. Akita, and T. Matsuishi Effects of L-arginine on the acute phase of strokes in three patients with MELAS Neurology, March 12, 2002; 58(5): 827 - 828. [Full Text] [PDF]
|
|
|
|
|
|
R. A. Santizo, H.-L. Xu, E. Galea, S. Muyskens, V. L. Baughman, and D. A. Pelligrino Combined Endothelial Nitric Oxide Synthase Upregulation and Caveolin-1 Downregulation Decrease Leukocyte Adhesion in Pial Venules of Ovariectomized Female Rats Stroke, February 1, 2002; 33(2): 613 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F HALTER, A S TARNAWSKI, A SCHMASSMANN, and B M PESKAR Cyclooxygenase 2{---}implications on maintenance of gastric mucosal integrity and ulcer healing: controversial issues and perspectives Gut, September 1, 2001; 49(3): 443 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Wood, L. F. Mattioli, and N. C. Gonzalez Hypoxia causes leukocyte adherence to mesenteric venules in nonacclimatized, but not in acclimatized, rats J Appl Physiol, September 1, 1999; 87(3): 873 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Domoki, R. Veltkamp, N. Thrikawala, G. Robins, F. Bari, T. M. Louis, and D. W. Busija Ischemia-reperfusion rapidly increases COX-2 expression in piglet cerebral arteries Am J Physiol Heart Circ Physiol, September 1, 1999; 277(3): H1207 - H1214. [Abstract] [Full Text] [PDF]
|
|