Summary
Previous studies have shown that nitric oxide (NO) inhibits specific agonist-induced
polymorphonuclear leukocyte (neutrophil) and platelet aggregation in vitro. However,
the inhibitory effects of NO on neutrophil interaction with the deeply injured arterial
wall under conditions of flow is unknown. Therefore, we investigated the influence
of NO derived from the endothelium on neutrophil and platelet interactions with the
downstream arterial media under controlled flow conditions. Porcine aortic media,
simulating deep arterial wall injury, was exposed to flowing porcine non-anticoagulated
arterial blood for 5 min at intermediate (1006 s1 ) and high (3397 s1 ) shear conditions, and deposition of radiolabeled neutrophils and platelets was quantified.
Neutrophil deposition on the exposed arterial media was reduced, by more than 30%,
by pretreatment of the endothelium with the physiological precursor of NO, L-arginine,
from 84.1 ± 13.7 to 57.4 ± 7.2 X 103 /cm2 (p < 0.05) at 1006 s*1 , and from 99.3 ± 9.8 to 65.5 ± 8.7 X KP/cm2 (p < 0.05) at 3397 s1 of shear rate, relative to control. Pretreatment of the endothelium with the inactive
stereoisomer D-arginine had no effect on neutrophil deposition. These specific inhibitory
effects of L-arginine were completely abolished by the inhibitor of NO synthesis,
N^-nitro- L-arginine methyl ester (l-NAME) at both shear rates. Endothelial pretreatment
with D-arginine, or with L-arginine, in the absence or presence of l-NAME, did not
significantly influence platelet interaction with the thrombogenic arterial media
at intermediate and high shear rates. These results indicate that NO derived from
the endothelium can modulate and has a greater influence on neutrophil, than on platelet,
interaction with the injured arterial wall exposing the media under conditions of
flow typical to moderately and severely stenosed arteries.
