title: Estimation of nitric oxide concentration in blood for different rates of generation. Evidence that intravascular nitric oxide levels are too low to exert physiological effects.
abstract: Endothelium-derived nitric oxide (NO) is a potent vasodilator in the cardiovascular system. Several lines of experimental evidence suggest that NO or NO equivalents may also be generated in the blood. However, blood contains a large amount of hemoglobin (Hb) in red blood cells (RBCs). The RBC-encapsulated Hb can react very quickly with NO, which is only limited by the rate of NO diffusion into the RBCs. It is unclear what the possible NO concentration levels in blood are and how the NO diffusion coefficient (D) and the permeability (Pm) of RBC membrane to NO affect the level of NO concentration. In this study, a steady-state concentration experimental method combined with a spherical diffusion model are presented for determining D and Pm and examining the effect of NO generation rate (V0) and hematocrit (Hct) on NO concentration. It was determined that Pm is 4.5 +/- 1.5 cm/s and D is 3410 +/- 50 microm2/s at 37 degrees C. Simulations based on experimental parameters show that, when the rate of NO formation is as high as 100 nm/s, the maximal NO concentration in blood is below 0.012 nM at Pm = 4.5 cm/s and Hct = 45%. Thus, it is unlikely that NO is directly exported or generated from the RBC as an intravascular signaling molecule, because its concentration would be too low to exert a physiological role. Furthermore, our results suggest that, if RBCs export NO bioactivity, this would be through NO-derived species that can release or form NO rather than NO itself.
authors.affiliation: Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio 43210, USA. Xiaoping.liu@osumc.edu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Yan
authors.forename: Kim L
authors.initials: KL
authors.lastname: Baskerville
authors.forename: Jay L
authors.initials: JL
authors.lastname: Zweier
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000379:methods; D004058:Diffusion; D004563:Electrochemistry; D004912:Erythrocytes / Q000378:metabolism*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D008956:Models, Chemical; D008962:Models, Theoretical; D009569:Nitric Oxide / Q000097:blood* / Q000737:chemistry* / Q000378:metabolism; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D006454:Hemoglobins; D009569:Nitric Oxide