Red Blood Cell-Mediated Hypoxic Vasodilatation

James, Philip E.; Tufnell-Barret, Timothy; Milsom, Alex B.; Frenneaux, Michael; Lang, Derek

doi:10.1161/res.95.2.e8

Cited by 10 publications

(5 citation statements)

References 6 publications

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“…One study showed that impaired endothelial production of NO during acute exercise stress in subjects with T2DM was the strongest predictor of exercise intolerance, in a multivariate regression model (3). The ability to conserve and transport NO via the plasma and red blood cells (RBC) (as described in an earlier section) may be dysfunctional in individuals with diabetes (99,147,212). One mechanism outlined for this deficiency is the preferential binding of NO to glycosylated RBC's and decrease in disassociation with changes in PO2.…”

Section: Inorganic Nitrate Supplementation and Exercise Performance In Diabetes Mellitusmentioning

confidence: 99%

Dietary nitrate supplementation in cardiovascular health: an ergogenic aid or exercise therapeutic?

Woessner

McIlvenna

Zevallos

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

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Oral consumption of inorganic nitrate, which is abundant in green leafy vegetables and roots, has been shown to increase circulating plasma nitrite concentration, which can be converted to nitric oxide in low oxygen conditions. The associated beneficial physiological effects include a reduction in blood pressure, modification of platelet aggregation, and increases in limb blood flow. There have been numerous studies of nitrate supplementation in healthy recreational and competitive athletes; however, the ergogenic benefits are currently unclear due to a variety of factors including small sample sizes, different dosing regimens, variable nitrate conversion rates, the heterogeneity of participants' initial fitness levels, and the types of exercise tests used. In clinical populations, the study results seem more promising, particularly in patients with cardiovascular diseases who typically present with disruptions in the ability to transport oxygen from the atmosphere to working tissues and reduced exercise tolerance. Many of these disease-related, physiological maladaptations, including endothelial dysfunction, increased reactive oxygen species, reduced tissue perfusion, and muscle mitochondrial dysfunction, have been previously identified as potential targets for nitric oxide restorative effects. This review is the first of its kind to outline the current evidence for inorganic nitrate supplementation as a therapeutic intervention to restore exercise tolerance and improve quality of life in patients with cardiovascular diseases. We summarize the factors that appear to limit or maximize its effectiveness and present a case for why it may be more effective in patients with cardiovascular disease than as ergogenic aid in healthy populations.

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Section: Inorganic Nitrate Supplementation and Exercise Performance In Diabetes Mellitusmentioning

confidence: 99%

Dietary nitrate supplementation in cardiovascular health: an ergogenic aid or exercise therapeutic?

Woessner

McIlvenna

Zevallos

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

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“…Male New Zealand white rabbits (1.8-2 Kg) were euthanized by intravenous injection of sodium pentobarbital. The aorta was harvested, and endothelium-intact rings were prepared for isometric tension recordings by mounting on a Radnoti vascular ring array (Harvard Apparatus, Holliston, MA, United States): 2 g resting tension, 37 °C, and Krebs (NaCl 118 mM, KCl 4.8 mM, KH 2 PO 4 1.2 mM, MgSO 4 1.2 mM, NaHCO 3 24 mM, glucose 11.0 mM, CaCl 2 2.5 mM, and disodium EDTA 0.03 mM); bath pO 2 was controlled by bubbling appropriate gas mixtures, as described (Pinder et al, (James et al, 2004). In brief, endotheliumintact rings were identified as those producing an ACh relaxation response during preconditioning that was >60% of the maximal induced tension (by PE); rings that did not produce this amount of relaxation were excluded.…”

Section: Rbc Vasoactivity (Hypoxic Vasodilation)mentioning

confidence: 99%

“…Frontiers in Physiology frontiersin.org baseline plateau tension (both under the above hypoxic bath conditions) (James et al, 2004).…”

Section: Rbc Vasoactivity (Hypoxic Vasodilation)mentioning

confidence: 99%

COVID-19 impairs oxygen delivery by altering red blood cell hematological, hemorheological, and oxygen transport properties

Rogers,

Brummet,

Safari

et al. 2024

Front. Physiol.

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Introduction: Coronavirus disease 2019 (COVID-19) is characterized by impaired oxygen (O2) homeostasis, including O2 sensing, uptake, transport/delivery, and consumption. Red blood cells (RBCs) are central to maintaining O2 homeostasis and undergo direct exposure to coronavirus in vivo. We thus hypothesized that COVID-19 alters RBC properties relevant to O2 homeostasis, including the hematological profile, Hb O2 transport characteristics, rheology, and the hypoxic vasodilatory (HVD) reflex.Methods: RBCs from 18 hospitalized COVID-19 subjects and 20 healthy controls were analyzed as follows: (i) clinical hematological parameters (complete blood count; hematology analyzer); (ii) O2 dissociation curves (p50, Hill number, and Bohr plot; Hemox-Analyzer); (iii) rheological properties (osmotic fragility, deformability, and aggregation; laser-assisted optical rotational cell analyzer (LORRCA) ektacytometry); and (iv) vasoactivity (the RBC HVD; vascular ring bioassay).Results: Compared to age- and gender-matched healthy controls, COVID-19 subjects demonstrated 1) significant hematological differences (increased WBC count—with a higher percentage of neutrophils); RBC distribution width (RDW); and reduced hematocrit (HCT), Hb concentration, mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC); 2) impaired O2-carrying capacity and O2 capacitance (resulting from anemia) without difference in p50 or Hb–O2 cooperativity; 3) compromised regulation of RBC volume (altered osmotic fragility); 4) reduced RBC deformability; 5) accelerated RBC aggregation kinetics; and (6) no change in the RBC HVD reflex.Discussion: When considered collectively, homeostatic compensation for these RBC impairments requires that the cardiac output in the COVID cohort would need to increase by ∼135% to maintain O2 delivery similar to that in the control cohort. Additionally, the COVID-19 disease RBC properties were found to be exaggerated in blood-type O hospitalized COVID-19 subjects compared to blood-type A. These data indicate that altered RBC features in hospitalized COVID-19 subjects burden the cardiovascular system to maintain O2 delivery homeostasis, which appears exaggerated by blood type (more pronounced with blood-type O) and likely plays a role in disease pathogenesis.

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“…Recently, it has been observed that levels of SNO-Hb are altered in several disease states characterized by disordered tissue oxygenation[108, 109, 153-160]. In addition, where examined, RBCs from such patients exhibit impaired vasodilatory capacity[90, 108, 109, 157, 159-161]. These data suggest that altered RBC-derived NO bioactivity may contribute to human pathophysiology.…”

Section: Conclusion: Blood Flow Disruption During Critical Illness Bymentioning

confidence: 99%

Red cell physiology and signaling relevant to the critical care setting

Said¹,

Rogers²,

Doctor

2015

Current Opinion in Pediatrics

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Purpose of Review Oxygen (O2) delivery, the maintenance of which is fundamental to supporting those with critical illness, is a function of blood O2 content and flow. Here, we review red blood cell (RBC) physiology relevant to disordered O2 delivery in the critically ill. Recent Findings Flow (rather then content) is the focus of O2 delivery regulation: O2 content is relatively fixed, whereas flow fluctuates by several orders of magnitude. Thus, blood flow volume and distribution vary to maintain coupling between O2 delivery and demand. The trapping, processing and delivery of nitric oxide (NO) by RBCs has emerged as a conserved mechanism through which regional blood flow is linked to biochemical cues of perfusion sufficiency. We will review conventional RBC physiology influencing O2 delivery (O2 affinity & rheology) and introduce a new paradigm for O2 delivery homeostasis based on coordinated gas transport and vascular signaling by RBCs. Summary By coordinating vascular signaling in a fashion that links O2 and NO flux, RBCs couple vessel caliber (and thus blood flow) to O2 need in tissue. Malfunction of this signaling system is implicated in a wide array of pathophysiologies and may be explanatory for the dysoxia frequently encountered in the critical care setting.

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Red Blood Cell-Mediated Hypoxic Vasodilatation

Cited by 10 publications

References 6 publications

Dietary nitrate supplementation in cardiovascular health: an ergogenic aid or exercise therapeutic?

Dietary nitrate supplementation in cardiovascular health: an ergogenic aid or exercise therapeutic?

COVID-19 impairs oxygen delivery by altering red blood cell hematological, hemorheological, and oxygen transport properties

Red cell physiology and signaling relevant to the critical care setting

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