Platelet inhibition by an L-arginine-derived substance released by IL-1 beta-treated vascular smooth muscle cells.
Experiments were performed to examine whether stimulation of cultured vascular smooth muscle cells by interleukin (IL)-1 beta would induce platelet inhibitory properties of these cells. Incubation of platelets with untreated rat aortic smooth muscle cells had no effect on thrombin-induced platelet aggregation. In contrast, incubation of platelets with IL-1 beta-pretreated smooth muscle cells or the perfusate from such cells resulted in the inhibition of thrombin-induced platelet aggregation. This effect was potentiated by superoxide dismutase and reversed by incubating the IL-1 beta-treated smooth muscle cells with NG-nitro-L-arginine (L-NNA) or by treating the platelets with methylene blue. Cytokine-treated smooth muscle cells inhibited thrombin-stimulated changes in platelet cytosolic ionized calcium, whereas untreated cells were without effect. Incubating platelets with IL-1 beta-treated smooth muscle cells resulted in a 10-fold increase in platelet guanosine 3',5'-cyclic monophosphate (cGMP) levels, whereas untreated smooth muscle cells had no effect. The elevation of platelet cGMP induced by the IL-1 beta-treated smooth muscle cells was prevented by exposing the cytokine-treated cells to L-NNA or by treating platelets with methylene blue. Treatment of smooth muscle cells with IL-1 beta also resulted in an eightfold increase in nitrite production, which was blocked when the cells were incubated with L-NNA. The addition of cycloheximide to smooth muscle cells during their incubation with IL-1 beta completely inhibited smooth muscle cell nitrite production, the effects of the smooth muscle cells on platelet cGMP levels, and platelet responses to thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)
Durante
W
W
Medical Service, Houston Veterans Affairs Medical Center, Texas.
Schini
V B
VB
Scott-Burden
T
T
Junquero
D C
DC
Kroll
M H
MH
Vanhoutte
P M
PM
Schafer
A I
AI
D000818:Animals; D001013:Aorta, Thoracic; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000097:blood; D004357:Drug Synergism; D007375:Interleukin-1 / Q000494:pharmacology*; D008751:Methylene Blue / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D019335:Nitroarginine; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D007375:Interleukin-1; D010975:Platelet Aggregation Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D013482:Superoxide Dismutase; D013917:Thrombin; D006152:Cyclic GMP; D008751:Methylene Blue