title: Modulation of nitric oxide bioavailability by erythrocytes.
abstract: Nitric oxide (NO) activates soluble guanylyl cyclase in smooth muscle cells to induce vasodilation in the vasculature. However, as hemoglobin (Hb) is an effective scavenger of NO and is present in high concentrations inside the red blood cell (RBC), the bioavailability of NO would be too low to elicit soluble guanylyl cyclase activation in the presence of blood. Therefore, NO bioactivity must be preserved. Here we present evidence suggesting that the RBC participates in the preservation of NO bioactivity by reducing NO influx. The NO uptake by RBCs was increased and decreased by altering the degree of band 3 binding to the cytoskeleton. Methemoglobin and denatured hemoglobin binding to the RBC membrane or cytoskeleton also were shown to contribute to reducing the NO uptake rate of the RBC. These alterations in NO uptake by the RBC, hence the NO bioavailability, were determined to correlate with the vasodilation of isolated blood vessels. Our observations suggest that RBC membrane and cytoskeleton associated NO-inert proteins provide a barrier for NO diffusion and thus account for the reduction in the NO uptake rate of RBCs.
authors.affiliation: Department of Chemical Engineering and Biomedical Engineering Interdepartmental Program, University of California, Los Angeles, CA 90095, USA.
authors.forename: K T
authors.initials: KT
authors.lastname: Huang
authors.forename: T H
authors.initials: TH
authors.lastname: Han
authors.forename: D R
authors.initials: DR
authors.lastname: Hyduke
authors.forename: M W
authors.initials: MW
authors.lastname: Vaughn
authors.forename: H
authors.initials: H
authors.lastname: Van Herle
authors.forename: T W
authors.initials: TW
authors.lastname: Hein
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Kuo
authors.forename: J C
authors.initials: JC
authors.lastname: Liao
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D001809:Blood Viscosity / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D004910:Erythrocyte Membrane / Q000502:physiology; D004912:Erythrocytes / Q000502:physiology*; D008706:Methemoglobin / Q000378:metabolism; D008833:Microcirculation / Q000502:physiology; D009569:Nitric Oxide / Q000097:blood*; D013552:Swine; D014783:Viscosity
chemical_list: D009569:Nitric Oxide; D008706:Methemoglobin; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid