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Am J Physiol Heart Circ Physiol (September 25, 2003). doi:10.1152/ajpheart.00532.2003
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Submitted on June 6, 2003
Accepted on September 15, 2003

Modulation of Endothelial Nitric Oxide Synthase Expression by Red Blood Cell Aggregation

Oguz K. Baskurt1*, Ozlem Yalcin1, Sadi Ozdem2, Jonathan K. Armstrong3, and Herbert J. Meiselman3

1 Department of Physiology, Akdeniz University Faculty of Medicine, Antalya, Turkey
2 Department of Pharmacology, Akdeniz University Faculty of Medicine, Antalya, Turkey
3 Department of Physiology and Biophysics, University of Southern California, Keck School of Medicine, Los Angeles, California, USA

* To whom correspondence should be addressed. E-mail: baskurt{at}akdeniz.edu.tr.

The effects of enhanced re d blood cell (RBC) aggregation on nitric oxide (NO) dependent vascular control mechanisms have been investigated in a rat exchange transfusion model. RBC aggregation for cells in native plasma was increased via a novel method using RBC covalently coated w ith a 13 kDa poloxamer copolymer (Pluronic F98); control experiments used RBC coated with a non-aggregating 8.4 kDa poloxamer (Pluronic F68). Rats exchange-transfused with aggregating RBC suspensions demonstrated significantly enhanced RBC aggregation throughout the five day follow-up period, with mean arterial blood pressure increasing gradually over this period. Arterial segments (~300 µm diameter) were isolated from gracilis muscle on the fifth day and mounted between two glass micropipettes in a special chamber equipped with pressure servo control system. Dose dependent dilation by acetylcholine and flow-mediated dilation of arterial segments pressurized to 30 mmHg and pre-constricted to 45-55% of the original diameter by phenylephrine were significantly blunted in rats with enhanced RBC aggregation. Both responses were totally abolished by non-specific NOS inhibitor (L-NAME) treatment of arterial segments, indicating that the responses were NO-related. Additionally, expression of eNOS protein was found to be decreased in muscle samples obtained from rats exchanged with aggregating cell suspensions. These results imply that enhanced RBC aggregation results in suppressed expression of NO synthesizing mechanisms, thereby leading to altered vasomotor tonus: the mechanisms involved most likely relate to decreased wall shear stresses due to decreased blood flow and/or increased axial accumulation of RBC.




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