title: Relationship among circulating hemoglobin, nitric oxide synthase activities and angiogenic poise in red- and white-blooded Antarctic notothenioid fishes.
abstract: Nitric oxide (NO)-mediated angiogenesis may play a role in establishing dense retinal vasculatures of Antarctic hemoglobinless icefishes (suborder: Notothenioidei). We hypothesized that loss of hemoglobin (Hb) leads to elevation in [NO] due to decreased degradation of the compound when the NO-scavenger Hb is absent, thereby inducing vascular growth. We found that total mass of NO metabolites, nitrite plus nitrate (NO(x)), in plasma is greater in icefishes than in red-blooded notothenioids [e.g. C. aceratus (Hb-), 22.7+/-2.9 microM; N. coriiceps (Hb+), 14.7+/-1.7 microM], suggesting a higher NO load in hemoglobinless animals. High NO levels do not appear to be a result of greater NO synthesis; we consistently measured lower activities of the enzyme catalyzing NO production, nitric oxide synthase, in tissues of icefishes than in Hb-expressing notothenioids [e.g. 96+/-10 and 216+/-39 pmol(min g wet wt)(-1) in brain tissue of C. aceratus (Hb-) and G. gibberifrons (Hb+), respectively]. Levels of mRNA for hypoxia-induced (HIF-1alpha and PHD2) and angiogenic genes (VEGF) were similar in red- and white-blooded species, indicating that vascular maintenance in adult animals does not require differences in angiogenic tone. This does not preclude a cause-and-effect relationship between absence of Hb and NO-mediated angiogenesis during earlier ontogenetic stages of icefishes.
authors.affiliation: School of Marine Sciences, University of Maine, 5751 Murray Hall, Orono, Maine 04469-5751, USA.
authors.forename: Jody M
authors.initials: JM
authors.lastname: Beers
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Borley
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Sidell
mesh_terms: D000818:Animals; D000864:Antarctic Regions; D055162:Biocatalysis; D005399:Fishes / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis*; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D011393:Procollagen-Proline Dioxygenase; D019001:Nitric Oxide Synthase