| Sign In to gain access to subscriptions and/or personal tools. |
Nitric Oxide Synthesis Inhibition and Role of P-selectin in Leukocyte Adhesion to Vascular TissuesDepartments of Medicine and Pediatrics, College of Medicine, University of Florida, Veterans Affairs Medical Center, Gainesville, Florida
Departments of Medicine and Pediatrics, College of Medicine, University of Florida, Veterans Affairs Medical Center, Gainesville, Florida
Departments of Medicine and Pediatrics, College of Medicine, University of Florida, Veterans Affairs Medical Center, Gainesville, Florida Background: This study was designed to examine the role of P-selectin expression in leuko cyte adhesion to endothelium caused by inhibition of nitric oxide synthesis.
Methods and Results: Rat aortic rings were treated with the nitric oxide synthesis inhibitor N Conclusions: These observations indicate that a reduction in nitric oxide synthesis enhances leukocyte adhesion to aortic endothelium and in visceral tissues. While P-selectin expression is evident in some of the experimental models of leukocyte adhesion to endothelium under conditions of nitric oxide inhibition, the role of P-selectin expression remains unclear.
Key Words: endothelium • leukocyte adhesion • nitric oxide • P-selectin.
Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 2, No. 2,
107-114 (1997) |
|||
 |
|
|
 |
Sign In to gain access to subscriptions and/or personal tools.
-nitro-L-arginine methyl ester (L-NAME) for 2 hours. Parallel sets of aortic rings were pretreated with the nitric oxide precursor L-arginine or posttreated with a specific mono clonal antibody against P-selectin. Some rings were used for determination of vasoreactivity in response to norepinephrine and acetylcholine, while other rings were incubated with autol ogous unlabeled leukocytes or Biotin-FITC labeled leukocytes for 30 minutes. Leukocyte adhesion to vascular endothelium was determined by scanning electron microscopy. L-NAME enhanced the contractile response in response to norepinephrine, suppressed the relaxant response to acetyleholine, promoted leukocyte adherence to the endothelium and resulted in P-selectin expression on the aortic endothelium. Pretreatment of aortic rings with L-arginine reversed the L-NAME-mediated changes in vasoreactivity in response to nore pinephrine and acetyleholine and attenuated the L-NAME-enhanced leukocyte adhesion to endothelial intima. P-selectin treatment, on the other hand, had no effect on L-NAME-medi ated changes. Intrtperitoneal administration of L-NAME resulted in a significant decrease in plasma nitrite level, a small, but significant, increase in lung and spleen myeloperoxidase activity, and a significant increase in leukocyte deposition in lung and spleen. The L-NAME- mediated increase in myelopcroxidase activity and leukocyte deposition in the spleen, but not in the lungs, was abolished by treatment of rats with the P-selectin antagonist CY 1503 administered 30 minutes prior to L-NAME.