title: Nitric oxide, S-nitrosothiols and hemoglobin: is methodology the key?
abstract: Two main hypotheses describe the role of hemoglobin in the regulation of nitric oxide (NO) bioavailability. It has been suggested that hemoglobin interacts with circulating NO, forming Fe-nitrosyl hemoglobin and then S-nitrosothiols, which deliver NO extracellularly by an allosterically regulated mechanism. Alternatively, the existence of diffusional barriers that protect NO from hemoglobin-mediated degradation has been proposed. The reliability of each model in vivo is supported by the detection of physiological hematic levels of S-nitrosohemoglobin. However, the measured concentrations of S-nitrosohemoglobin are largely divergent between the two models. Moreover, recent reports suggest that circulating levels of S-nitrosohemoglobin in human blood could be significantly lower than assessed previously. We suggest that solving the methodological controversies that make the field of NO research a 'minefield', even for skilled analysts, is fundamental to understanding the role of S-nitrosothiols in the vasculature.
authors.affiliation: Department of Neuroscience, Pharmacology Section, Via A. Moro 4, University of Siena, 53100 Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Giustarini
authors.forename: Aldo
authors.initials: A
authors.lastname: Milzani
authors.forename: Roberto
authors.initials: R
authors.lastname: Colombo
authors.forename: Isabella
authors.initials: I
authors.lastname: Dalle-Donne
authors.forename: Ranieri
authors.initials: R
authors.lastname: Rossi
mesh_terms: D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism*; D026403:S-Nitrosothiols / Q000097:blood / Q000378:metabolism*
chemical_list: D006454:Hemoglobins; D020030:Nitric Oxide Donors; D026403:S-Nitrosothiols; D009569:Nitric Oxide