Effects of endothelium-derived relaxing factor/nitric oxide on
platelet surface glycoproteins.
Michelson, Alan D., Stephen E. Benoit, Mark I. Furman, William L.
Breckwoldt, Michael J. Rohrer, Marc R. Barnard, and Joseph Loscalzo.
Center for Platelet Function Studies, Cardiovascular Thrombosis
Research Center, Divisions of Cardiovascular Medicine and Vascular
Surgery, Departments of Pediatrics, Medicine, Cell Biology, and
Surgery, University of Massachusetts Medical School, Worcester, MA
01655 and Whitaker Cardiovascular Institute and Department of
Medicine, Boston University School of Medicine, Boston, MA 02118
APStracts 3:0055H, 1996.
We examined the effect of endothelium-derived relaxing factor
(EDRF)/nitric oxide (NO) on platelet surface glycoproteins. As
determined by flow cytometry, in both a washed platelet system and
platelet-rich plasma, the EDRF congener (S-nitroso-N-acetylcysteine)
markedly inhibited both the thrombin-induced and the (stable
thromboxane A2 analog) U46619-induced up-regulation of P-selectin
([alpha] granule protein), CD63 (lysosomal protein), and the GPIIb
-IIIa complex (fibrinogen receptor), but minimally inhibited down
-regulation of the GPIb-IX complex (von Willebrand factor receptor).
The inhibitory effects of EDRF were markedly reduced in whole blood
or by the addition of washed erythrocytes. Platelets in whole blood
were still responsive to cyclic guanosine mono phosphate (cGMP) as
shown by complete inhibition of P-selectin up-regulation by the
stable analog dibutyryl cGMP. These data suggest that: 1) cGMP
negatively regulates the platelet surface expression of P-selectin,
CD63, and the GPIIb-IIIa complex, but not the platelet surface
expression of the GPIb-IX complex. 2) Hemoglobin within erythrocytes
inhibits the effects of EDRF/NO on platelet surface glycoproteins.
Received 3 April 1995; accepted in final form 2 October 1995.
APS Manuscript Number H320-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96