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Article type: Research Article
Authors: Ulker, Pinar | Gunduz, Filiz | Meiselman, Herbert J. | Baskurt, Oguz K.
Affiliations: Department of Physiology, Faculty of Medicine, Akdeniz University, Antalya, Turkey | Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA | School of Medicine, Koc University, Istanbul, Turkey
Note: [] Diseased.
Abstract: Red blood cells (RBC) possess a functional nitric oxide synthase (NOS) enzyme located in the cell membrane and cytoplasm. It has previously been observed that shear stress acting on RBC activates NOS and causes enhanced NO export. The aim of the present study was to investigate the physiological importance (e.g., in local blood flow regulation) of RBC-derived NO stimulated by application of shear stress. Blood samples and arterial vessel segments were obtained from Wistar rats; RBC suspensions were adjusted to a hematocrit of 0.1 l/l using Krebs solution. In order to apply shear stress to the RBC suspensions they were continuously flowed through a small-bore glass tube for 20 minutes at a wall shear stress of 2 Pa. The RBC suspensions were then perfused through endothelium denuded small mesenteric arteries having a diameter of ~300 μm under both high oxygen (PO2 ~130 mmHg) and hypoxic conditions. Perfusion of vessel segments with sheared RBC suspensions caused a significant dilation response under hypoxic conditions but not at high oxygen levels. Incubation of RBC suspensions with the non-specific NOS inhibitor L-NAME (10−3 M) prior to shear stress application abolished this dilation response. Our results indicate that NO released from RBC due to shear stress activation of NOS results in vasodilation of vessel segments under hypoxic conditions, and strongly suggest that NO originating from RBC may have a functional role in local blood flow regulation.
Keywords: Erythrocyte NOS, mechanical stimulation, NOS activation, blood flow regulation
DOI: 10.3233/CH-2012-1618
Journal: Clinical Hemorheology and Microcirculation, vol. 54, no. 4, pp. 357-369, 2013
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