Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions.
BACKGROUND
Nitric oxide (NO) has been identified as endothelium-derived relaxing factor (EDRF), which, in addition to its relaxant effects on vascular smooth muscle cells, is also a potent inhibitor of platelet aggregation. An inhibitory role on platelet adhesion has been suggested from experiments with washed platelets under static conditions. We have determined whether endothelium-derived and exogenous NO also regulates platelet adhesion in whole blood under flow conditions.


RESULTS
The effect of endothelium-derived NO was studied by the addition of specific inhibitors of NO production, L-N-monomethyl arginine (L-NMMA) and N-iminoethyl-L-ornithine (L-NIO), to a perfusion system in which both endothelial cells and their matrices were present. A concentration-dependent increase in platelet adhesion to the matrix was found with a maximum inhibition at a concentration of 2 mM L-NMMA and 0.1 mM L-NIO. The effect was dependent on the presence of endothelial cells, because no increase in platelet adhesion was observed in their absence. The effect of exogenous NO was tested in a specially devised perfusion system in which the NO was introduced at the site of adhesion by means of a porous membrane on which an extracellular matrix of endothelial cells was present. Inhibition of platelet adhesion by NO was found at all shear rates tested and after all perfusion periods.


CONCLUSIONS
These results demonstrate that NO is a potent inhibitor of platelet adhesion under flow conditions and thereby contributes to the regulatory role of vascular endothelial cells on platelet-vessel wall interaction.
de Graaf
J C
JC
Department of Hematology, University Hospital Utrecht, The Netherlands.
Banga
J D
JD
Moncada
S
S
Palmer
R M
RM
de Groot
P G
PG
Sixma
J J
JJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001775:Blood Circulation / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D001120:Arginine; D009952:Ornithine