Platelet aggregation may not be a prerequisite for collagen-stimulated platelet generation of nitric oxide

• Published in: Biochimica et biophysica acta Vol. 1473; no. 2; pp. 286 - 292
• Main Authors: Smith, Christopher C.T, Stanyer, Lee, Cooper, Michael B, Betteridge, D.John
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 27.12.1999
• Subjects: Aggregation; Blood Platelets - drug effects; Blood Platelets - metabolism; Collagen - pharmacology; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme Inhibitors - pharmacology; Humans; NG-Nitroarginine Methyl Ester - pharmacology; Nitrate; Nitric oxide; Nitric Oxide - metabolism; Nitrite; Platelet; Platelet Aggregation - drug effects; Sensitivity and Specificity; Serotonin; Serotonin - metabolism; Aggregation; Platelet; Nitrate; Nitrite; Serotonin; Nitric oxide
• ISSN: 0304-4165; 0006-3002; 1872-8006; 1878-2434
• DOI: 10.1016/S0304-4165(99)00202-0

By determining the sum of the supernatant concentrations of nitrite and nitrate the stimulated generation of nitric oxide (NO) by human washed platelets induced by a range of fibrillar collagen concentrations (0.0156–25 μg ml −1) was investigated. Platelet serotonin (5-hydroxytryptamine, 5-HT) efflux and platelet aggregation were also measured. Under resting conditions (0 μg ml −1 collagen) platelet NO release was equivalent to 1.06±0.17 nmol per 10 8 platelets. Maximal NO release, equivalent to 2.1±0.37 nmol per 10 8 platelets, was observed with only 0.0625 μg ml −1 collagen ( P<0.02, stimulated vs. resting release), higher collagen concentrations producing no further increases in platelet NO output. By contrast, maximal platelet aggregation and 5-HT efflux did not occur until collagen concentrations of 2.5 μg ml −1 and 10–25 μg ml −1, respectively, had been achieved. l-NAME (1 mmol l −1) and l-NMMA (1 mmol l −1) inhibited stimulated platelet NO generation by 78±6% and 72%, respectively. Contrasting with fibrillar collagen, fibrillar β-amyloid protein had no effect on platelet NO generation, or on 5-HT efflux or aggregation. These data perhaps indicate that NO generation by human platelets is stimulated by concentrations of fibrillar collagen insufficient to elicit an aggregatory response. Such a mechanism could operate in vivo to inhibit platelet aggregation which might otherwise be induced by low concentrations of circulating agonists.