Inhibition of intravascular platelet aggregation by endothelium-derived
relaxing factor: reversal by red blood cells
DS Houston, P Robinson and JM Gerrard
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Studies were performed to determine whether endothelium-derived relaxing
factor (EDRF) can inhibit platelet aggregation within the vascular lumen,
and if so, whether the inhibition persists in the presence of red blood
cells (RBCs). Canine femoral arteries mounted in an organ bath were
perfused with physiologic saline solution to which acetylsalicylic acid was
added to block prostacyclin formation. During contraction with
phenylephrine, addition of acetylcholine to the perfusing solution to evoke
EDRF release relaxed the vessel wall. Washed human platelets labeled with
14C-5-hydroxytryptamine were added to the perfusing solution, and activated
by thrombin infused via a branch vessel. The perfusate was collected
downstream and centrifuged; the fraction of 14C-5-hydroxytryptamine
appearing in the supernatant reflected the degree of platelet activation.
Stimulation of EDRF release with acetylcholine inhibited
14C-5-hydroxytryptamine release. Hemoglobin (Hb) (10(-5) mol/L) blocked
vascular relaxation and platelet- inhibition. RBCs at a hematocrit of 10%
(treated with echothiophate to block erythrocyte cholinesterase) did not
prevent relaxation but reversed the platelet inhibition. Lower hematocrits
did not completely block the inhibition. Thus, erythrocyte Hb may modulate
the inhibition of intraluminal platelet aggregation by EDRF.
Volume 76,
Issue 5,
pp. 953-958,
09/01/1990
Copyright © 1990 by The American Society of Hematology
