Microvascular dysfunction induced by nonsteroidal anti-inflammatory
drugs: role of leukocytes.
Kurose, Iwao, Robert Wolf, Masayuki Miyasaka, Donald C. Anderson, and
D. Neil Granger.
Departments of Physiology and Medicine, Center of Excellence in
Arthritis and Rheumatology, Louisiana State University Medical
Center, Shreveport, LA, 71130-3932, Department of Bioregulation,
Osaka University Medical School, Discovery Research, UpJohn
Laboratories, Kalamazoo, MI
APStracts 2:0170G, 1995.
The objectives of this study were to determine whether 1) the
leukocyte-endothelial cell adhesion observed in venules exposed to
nonsteroidal anti-inflammatory drugs (NSAIDs) is accompanied by
enhanced albumin extravasation, and 2) leukocytes mediate this
endothelial cell barrier dysfunction. Intravital video microscopy was
used to monitor leukocyte-endothelial cell adhesion and the leakage
of FITC- labelled albumin in rat mesenteric venules exposed to either
indomethacin or aspirin. Both NSAIDs induced the recruitment of
adherent and emigrated leukocytes, with temporally related increases
in albumin leakage. Agents that effectively decreased or prevented
the NSAID- induced leukocyte adherence/emigration (leukotriene B4
receptor antagonist or adhesion molecule-specific monoclonal
antibodies) also blocked the corresponding albumin leakage response.
These findings indicate that adherent and/or emigrating leukocytes
mediate the early endothelial cell barrier dysfunction elicited by
NSAIDs.
Received 27 April 1995; accepted in final form 3 August 1995.
APS Manuscript Number G177-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.