(Circulation. 1995;92:3513-3519.)
© 1995 American Heart Association, Inc.
Articles |
Exposure to Shear Stress Alters Endothelial Adhesiveness
Role of Nitric Oxide
From the Section of Vascular Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, Calif.
Correspondence to John P. Cooke, MD, PhD, Director, Section of Vascular Medicine, Division of Cardiovascular Medicine Stanford University, 300 Pasteur Dr, Stanford, CA 94305-5246.
Background Shear stress increases the release of nitric oxide (NO) by endothelial cells (ECs). We and others have provided evidence that endothelium-derived NO inhibits monocyte adhesion to the vessel wall. We therefore hypothesized that previous exposure to shear stress would inhibit endothelial adhesiveness for monocytes by virtue of its effect to increase NO release.
Methods and Results Confluent monolayers of bovine aortic
endothelial cells, human aortic
endothelial cells, or human venous
endothelial cells were exposed to laminar fluid flow.
Culture media were collected for measurement of NO (by
chemiluminescence) and the prostacyclin metabolite
6-keto-prostaglandin
F1
. NOx and
6-keto-prostaglandin F1
accumulated in the conditioned medium during laminar fluid flow from 30
minutes to 24 hours in a time-dependent fashion. In another set of
studies, ECs previously exposed to flow or to static conditions were
washed with Hanks' buffer and exposed to THP-1 cells for 30 minutes.
Adherent cells were counted by microscopy. Previous exposure to flow
reduced endothelial adhesiveness for monocytes by 50%
(P<.05). The effect of flow on endothelial
adhesiveness occurred within 30 minutes. This effect was abrogated by
nitro-L-arginine (an antagonist of NO
synthesis), as well as by
tetraethylammonium ion (an
antagonist of the flow-activated potassium
channel); the effects of these inhibitors were reversed by
the NO donor SPM-5185. Although the cyclo-oxygenase
inhibitor indomethacin totally inhibited
the flow-induced production of prostacyclin by ECs, it
minimally affected adherence of THP-1 cells. The early effect of flow
on endothelial adhesiveness was not mediated by
alterations in the expression of the endothelial
adhesion molecules VCAM-1 or ICAM-1 as assessed by fluorescent
activated cell sorting.
Conclusions Shear stress alters endothelial adhesiveness for monocytes; at early time points, this effect is largely due to flow-stimulated release of NO and, to a lesser extent, prostacyclin. This effect of flow occurs within 30 minutes and is probably due to alterations in the signal transduction or activation state (rather than the expression) of endothelial adhesion molecules.
Key Words: atherosclerosis • endothelium-derived factors • leukocytes • flow
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