Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med 2002 Dec;8(12):1383-9
Date
11/12/2002Pubmed ID
12426562DOI
10.1038/nm1202-799Scopus ID
2-s2.0-0036908599 (requires institutional sign-in at Scopus site) 1058 CitationsAbstract
Although the deleterious vasoconstrictive effects of cell-free, hemoglobin-based blood substitutes have been appreciated, the systemic effects of chronic hemolysis on nitric oxide bioavailability have not been considered or quantified. Central to this investigation is the understanding that nitric oxide reacts at least 1,000 times more rapidly with free hemoglobin solutions than with erythrocytes. We hypothesized that decompartmentalization of hemoglobin into plasma would divert nitric oxide from homeostatic vascular function. We demonstrate here that plasma from patients with sickle-cell disease contains cell-free ferrous hemoglobin, which stoichiometrically consumes micromolar quantities of nitric oxide and abrogates forearm blood flow responses to nitric oxide donor infusions. Therapies that inactivate plasma hemoglobin by oxidation or nitric oxide ligation restore nitric oxide bioavailability. Decompartmentalization of hemoglobin and subsequent dioxygenation of nitric oxide may explain the vascular complications shared by acute and chronic hemolytic disorders.
Author List
Reiter CD, Wang X, Tanus-Santos JE, Hogg N, Cannon RO 3rd, Schechter AN, Gladwin MTAuthor
Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAnemia, Sickle Cell
Biological Availability
Heme
Hemocyanins
Hemoglobins
Hemolysis
Humans
Middle Aged
Nitric Oxide
Oxidation-Reduction
