The dual roles of red blood cells in tissue oxygen delivery: oxygen carriers and regulators of local blood flow

Frank, Jason

doi:10.1242/jeb.023697

Cited by 209 publications

(165 citation statements)

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“…Assuming a 30 -40% hematocrit in vivo and a linear relationship between [ATP]e and hematocrit, activation of the cAMP pathway in circulating erythrocytes would generate up to 1 M ATPe, a concentration suitable for activating most P2 receptors in erythrocytes as well as in endothelial cells (44,45,58). This is important inasmuch as activation of P2Y 1 and P2Y 2 receptors in endothelial cells induces the generation and release of nitric oxide (59,60), followed by relaxation of smooth muscles surrounding the capillaries of the microcirculation (3) and a corresponding relaxation of vascular tone. In the context of Fig.…”

Section: Discussionmentioning

confidence: 99%

Homeostasis of Extracellular ATP in Human Erythrocytes

Montalbetti

Denis

Pignataro

et al. 2011

Journal of Biological Chemistry

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We explored the intra-and extracellular processes governing the kinetics of extracellular ATP (ATPe) in human erythrocytes stimulated with agents that increase cAMP. Using the luciferinluciferase reaction in off-line luminometry we found both direct adenylyl cyclase activation by forskolin and indirect activation through ␤-adrenergic stimulation with isoproterenol-enhanced [ATP]e in a concentration-dependent manner. A mixture (3V) containing a combination of these agents and the phosphodiesterase inhibitor papaverine activated ATP release, leading to a 3-fold increase in [ATP]e, and caused increases in cAMP concentration (3-fold for forskolin ؉ papaverine, and 10-fold for 3V). The pannexin 1 inhibitor carbenoxolone and a pannexin 1 blocking peptide ( Both for soluble luciferase and proA-luc, ATP efflux was fully blocked by carbenoxolone, pointing to a 3V-induced mechanism of ATP release mediated by pannexin 1. Ecto-ATPase activity was extremely low (ϳ28 fmol ؋ (10 6 cells min) ؊1 ), but nevertheless physiologically relevant considering the high density of erythrocytes in human blood.All cell types appear to possess mechanisms that enable a controlled, nonlytic release of ATP, that is, a release not involving cell membrane rupture, and which occurs in response to osmotic, mechanical, and/or neurohormonal stimuli (1). Specifically human erythrocytes release ATP following exposure to ␤-adrenergic stimulation, mechanical deformation, reduced oxygen tension, or acidosis (2). All of these represent physiological conditions to which erythrocytes are exposed in the vasculature, e.g. when passing through constricted vessels or in the contracting striated muscle (3). Once in the extracellular medium, extracellular ATP (ATPe) 5 can trigger different cellular responses by interacting with P receptors on the cell surface while at the same time its concentration is controlled by the activities of one or more ectonucleotidases (4, 5). Several reports published over recent years have shown that an increase in intracellular cyclic AMP (cAMP) concentration triggered ATP release from human erythrocytes (6, 7). Receptor-mediated ATP release in human erythrocytes involves activation of heterotrimeric G proteins G s or G i/o (3, 8, 9). Regarding the G s pathway, activation of ␤-adrenergic receptors by various agonists was reported to stimulate adenylyl cyclase, with concomitant increases in cAMP levels and protein kinase A activity (6, 10). Moreover, direct activation of adenylyl cyclase by forskolin resulted in both ATP release and cAMP increases in human and rabbit erythrocytes (6).Despite the accumulated knowledge regarding the intracellular signaling events mediating ATP release, comparatively little is known regarding the processes governing the kinetics of ATPe accumulation at the surface in animal cells (11,12), with rates of intracellular ATP release and extracellular ATP hydrolysis being the main actors. The human non-nucleated erythrocyte is an excellent model in this respect, because it lacks intracellular compartments and...

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Section: Discussionmentioning

confidence: 99%

Homeostasis of Extracellular ATP in Human Erythrocytes

Montalbetti

Denis

Pignataro

et al. 2011

Journal of Biological Chemistry

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“…In mammals, it has been proposed that Hb nitrosated at Cys93 of the  chain represents a blood-borne NO activity that can be released upon deoxygenation in hypoxic tissues and contribute to hypoxic vasodilation (Jia et al, 1996). Fish Hbs do not contain this particular cysteine but may be nitrosated at other cysteines (Jensen, 2009b). Goldfish Hb contains four Cys residues in the  chain, of which three are internal whereas one is placed in a surface crevice of the Hb molecule (Reischl et al, 2007) and therefore is potentially available for S-nitrosation.…”

Section: Influence Of Hypoxia On No Metabolitesmentioning

confidence: 99%

Nitric oxide metabolites in goldfish under normoxic and hypoxic conditions

Hansen

Frank

2010

Journal of Experimental Biology

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SUMMARYNitric oxide (NO), produced by nitric oxide synthases (NOS enzymes), regulates multiple physiological functions in animals. NO exerts its effects by binding to iron (Fe) of heme groups (exemplified by the activation of soluble guanylyl cyclase) and by Snitrosylation of proteins -and it is metabolized to nitrite and nitrate. Nitrite is used as a marker for NOS activity but it is also a NO donor that can be activated by various cellular proteins under hypoxic conditions. Here, we report the first systematic study of NO metabolites (nitrite, nitrate, S-nitroso, N-nitroso and Fe-nitrosyl compounds) in multiple tissues of a non-mammalian vertebrate (goldfish) under normoxic and hypoxic conditions. NO metabolites were measured in blood (plasma and red cells) and heart, brain, gill, liver, kidney and skeletal muscle, using highly sensitive reductive chemiluminescence. The severity of the chosen hypoxia levels was assessed from metabolic and respiratory variables. In normoxic goldfish, the concentrations of NO metabolites in plasma and tissues were comparable with values reported in mammals, indicative of similar NOS activity. Exposure to hypoxia [at P O2 (partial pressure of O 2 ) values close to and below the critical P O2 ] for two days caused large decreases in plasma nitrite and nitrate, which suggests reduced NOS activity and increased nitrite/nitrate utilization or loss. Tissue NO metabolites were largely maintained at their tissue-specific values under hypoxia, pointing at nitrite transfer from extracellular to intracellular compartments and cellular NO generation from nitrite. The data highlights the preference of goldfish to defend intracellular NO homeostasis during hypoxia.

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“…Such endurance is especially required for the following: in different competitions; in trainings; in everyday life of studentsathletes [42,53]. In such case EPB is a convenient object for such researches: they participate in processes, connected with sustaining of the whole organism's homeostasis [34,44,49]. In our research we found that in 57% of 2 nd group's volleyball players, under influence of PL max negative morphological changes of EPB appear.…”

Section: Discussionmentioning

confidence: 54%

Special aspects of hemo-dynamic and reaction of erythrocytes in blood to standard physical load of different qualification female volleyball players

Pоpеl

Tsap

Yatciv

et al. 2017

PPS

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Purpose:to study the aspects of organism's cardio-hemo-dynamic and blood erythrocytes reaction of female volleyball players to standard physical load. Material:with functional methods we studied cardio-hemo-dynamic and with the help of scanning electronic microscopy -erythrocytes' structure in 18 female volleyball players of different qualification (age -22.0±0.60 years). Results:it was found that maximal physical load causes substantial changes in cardio-hemo-dynamic, which depend on female volleyball players' qualification. These changes have intrinsic to them type of blood circulation system reacting, which is manifested in the following: appropriate changes of some indicators; natural changes of periphery blood erythrocytes. In the article possible mechanisms of realization of female volleyball players' organism's typological features, depending on blood circulation type and erythrocytes' conformation, are discussed. Conclusions:In relaxed state all female volleyball players have non-uniform cardio-hemo-dynamic of blood circulation.With hyper-dynamic blood circulation type, higher indicators of strike and minute blood volume were observed. With hypo-kinetic blood circulation type the opposite picture was observed: indicators of strike and minute blood volume, heart index, load on cardio-vascular system in different periods of day were low.

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The dual roles of red blood cells in tissue oxygen delivery: oxygen carriers and regulators of local blood flow

Cited by 209 publications

References 57 publications

Homeostasis of Extracellular ATP in Human Erythrocytes

Homeostasis of Extracellular ATP in Human Erythrocytes

Nitric oxide metabolites in goldfish under normoxic and hypoxic conditions

Special aspects of hemo-dynamic and reaction of erythrocytes in blood to standard physical load of different qualification female volleyball players

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