ENDOTHELIUM-DERIVED NITRIC-OXIDE DECREASES POLYMORPHONUCLEAR LEUKOCYTE INTERACTION WITH THE DEEPLY INJURED ARTERIAL-WALL UNDER INTERMEDIATEAND HIGH-SHEAR CONDITIONS

Previous studies have shown that nitric oxide (NO) inhibits specific a gonist-induced polymorphonuclear leukocyte (neutrophil) and platelet a ggregation in vitro. However, the inhibitory effects of NO on neutroph il interaction with the deeply injured arterial wall under conditions of flow is unknown. Therefore, we investigated the influence of NO der ived from the endothelium on neutrophil and platelet interactions with the downstream arterial media under controlled now conditions. Porcin e aortic media, simulating deep arterial wall injury, was exposed to f lowing porcine non-anticoagulated arterial blood for 5 min at intermed iate (1006 s(-1)) and high (3397 s(-1)) shear conditions, and depositi on of radiolabeled neutrophils and platelets was quantified. Neutrophi l deposition an the exposed arterial media was reduced, by more than 3 0%, by pretreatment of the endothelium with the physiological precurso r of NO, L-arginine, from 84.1 +/- 13.7 to 57.4 +/- 7.2 X 10(3)/cm(2) (p < 0.05) at 1006 s(-1), and from 99.3 +/- 9.8 to 65.5 +/- 8.7 X 10(3 )/cm(2) (p < 0.05) at 3397 s(-1) of shear rate, relative to control. P retreatment of the endothelium with the inactive stereoisomer D-argini ne had no effect on neutrophil deposition. These specific inhibitory e ffects of L-arginine were completely abolished by the inhibitor of NO synthesis, N-omega-nitro-L-arginine methyl ester (L-NAME) at both shea r 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 intermed iate and high shear rates. These results indicate that NO derived from the endothelium can modulate and has a greater influence on neutrophi l, than an platelet, interaction with the injured arterial wall exposi ng the media under conditions of flow typical to moderately and severe ly stenosed arteries.