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Platelets inhibit the induction of nitric oxide synthesis by interleukin-1
beta in vascular smooth muscle cells
W Durante, VB Schini, MH Kroll, S Catovsky, T Scott-Burden, JG White, PM Vanhoutte and AI Schafer
Medical Service, Houston Veterans Affairs Medical Center, TX 77030.
We have investigated the role of platelets in regulating the hemostatic and
vasomotor properties of vascular smooth muscle. Experiments were performed
to examine the effect of the releasate from activated platelets on the
production of nitric oxide from interleukin-1 beta (IL- 1 beta)-treated
cultured rat aortic smooth muscle cells. Treatment of vascular smooth
muscle cells with IL-1 beta resulted in significant accumulation of nitrite
in the culture media and in marked elevation of intracellular cyclic
guanosine monophosphate (GMP) levels. The releasate from
collagen-aggregated platelets blocked the IL-1 beta- mediated production of
nitrite and the accumulation of cyclic GMP in smooth muscle cells in a
platelet number-dependent manner. In functional assays, the perfusates from
columns containing IL-1 beta- treated smooth muscle cells relaxed detector
blood vessels without endothelium and the addition of IL-1 beta-treated
smooth muscle cells to suspensions of platelets inhibited their
thrombin-induced aggregation. The simultaneous treatment of smooth muscle
cells with IL- 1 beta and the platelet releasate abolished both the
vasorelaxing activities of the perfusates and the inhibition of platelet
aggregation. Platelet releasates treated with a neutralizing antibody to
platelet-derived growth factor (PDGF) failed to block IL-1 beta- induced
nitric oxide production by the smooth muscle cells, as measured by both
biochemical and functional assays. The platelet releasate from a patient
with gray platelet syndrome likewise failed to block IL-1 beta-induced
nitrite release by smooth muscle cells. These results demonstrate that
platelets downregulate the production of nitric oxide by IL-1 beta-treated
vascular smooth muscle cells through the release of PDGF. This effect may
represent a novel mechanism by which platelets regulate vasomotor tone and
thrombus formation at sites of vascular injury.
Volume 83,
Issue 7,
pp. 1831-1838,
04/01/1994
Copyright © 1994 by The American Society of Hematology

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