EFFECTS OF NITRIC OXIDE EDRF ON PLATELET SURFACE GLYCOPROTEINS/

We examined the effects of nitric oxide (NO)/endothelium-derived relax ing factor (EDRF) on platelet surface glycoproteins (GP). As determine d by flow cytometry, in both a washed platelet system and platelet-ric h plasma, the EDRF congener (S-nitroso-N-acetylcysteine) markedly inhi bited both the thrombin-induced and the (stable thromboxane A(2) analo gue) U-46619-induced upregulation of P-selectin (alpha-granule protein ), CD63 (lysosomal protein), and the GPIIb-IIIa complex (fibrinogen re ceptor) but minimally inhibited downregulation 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 erythrocy tes. Platelets in whole blood were still responsive to guanosine 3',5' -cyclic monophosphate (cGMP), as shown by complete inhibition of P-sel ectin upregulation by the stable analogue N-6,2'-O-dibutyryl cGMP. The se data suggest that 1) cGMP negatively regulates the platelet surface expression of P-selectin, CD63, and the GPIIb-IIIa complex but not th e platelet surface expression of the GPIb-IX complex and 2) hemoglobin within erythrocytes inhibits the effects of EDRF/NO on platelet surfa ce glycoproteins.