Abstract
Endothelium-derived relaxing factor (EDRF) or nitric oxide (NO) biosynthesis fromL-arginine occurs in the endothelium and platelets and may modulate plate-let function and contribute to thromboresistance in the vessel wall. A rat model was used to evaluate selective accumulation of111In-labeled platelets in the pulmonary microcirculation following the administration of collagen, adenosine 5′-diphosphate (ADP) or thrombin. Platelet aggregation was monitored continuously over the thorax using a microcomputer-based system. Sodium nitroprusside, a stimulator of soluble guanylate cyclase and zaprinast, a phosphodiesterase V inhibitor, both known to cause accumulation of cyclic guanosine monophosphate, exhibited moderate inhibitory activity, which was shared byL-arginine. NG-monomethyl-L-arginine (L-NMMA; 1 mg/kg/min), an inhibitor of EDRF(NO), potentiated the aggregatory response to collagen at an intravenous dose of 100 µg/kg but not at one of 30 µg/kg. D-NMMA had no such effect. The augmenting effect of L-NMMA was abolished byL-arginine. NG-nitro-L-arginine methyl ester (L-NAME; 0.1 mg/kg/min) also markedly augmented the collagen-induced platelet response, and, at higher doses, all treated animals died upon collagen challenge. Both L-NMMA and L-NAME did not affect the responses to ADP and thrombin. The results suggest that in the intact vascular system, basal release of EDRF(NO) is not critically involved in modulation of platelet function but becomes a significant factor when platelets are exposed to great amounts of collagen fibrils.
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Chiu, P.J.S., Tetzloff, G. EDRF(NO)-mediated modulation of collagen-induced platelet accumulation in rat pulmonary microcirculation. J Biomed Sci 1, 43–48 (1993). https://doi.org/10.1007/BF02258338
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DOI: https://doi.org/10.1007/BF02258338