Nitric oxide in red blood cell adaptation to hypoxia

Abstract

Nitric oxide (NO) appears to be involved in virtually every aspect of cardiovascular biology. Most attention has been focused on the role of endothelial-derived NO in basal blood flow regulation by relaxing vascular smooth muscle; however, it is now known that NO derived from red blood cells (RBCs) plays a fundamental role in vascular homeostasis by enhancing oxygen (O2) release at the cellular and physiological level. Hypoxia is an often seen problem in diverse conditions; systemic adaptations to hypoxia permit people to adjust to the hypoxic environment at high altitudes and to disease processes. In addition to the cardiopulmonary and hematologic adaptations that support systemic O2 delivery in hypoxia, RBCs assist through newly described NO-based mechanisms, in line with their vital role in O2 transport and delivery. Furthermore, to increase the local blood flow in proportion to metabolic demand, NO regulates membrane mechanical properties thereby modulating RBC deformability and O2 carrying-releasing function. In this review article, we focus on the effect of NO bioactivity on RBC-based mechanisms that regulate blood flow and RBC deformability. RBC adaptations to hypoxia are summarized, with particular attention to NO-dependent S-nitrosylation of membrane proteins and hemoglobin (S-nitrosohemoglobin). The NO/S-nitrosylation/RBC vasoregulatory cascade contributes fundamentally to the molecular understanding of the role of NO in human adaptation to hypoxia and may inform novel therapeutic strategies.

A Translational In Vivo and In Vitro Metabolomic Study Reveals Altered Metabolic Pathways in Red Blood Cells of Type 2 Diabetes

“…Moreover, cells may be less sensitive to on-off changes than plasma/serum samples, reducing false positive/negative results [ 37 ]. Furthermore, metabolomics profiling of RBCs can improve the study on the effect of hypoxia in T2D since these cell act as oxygen delivering systems [ 38 , 39 , 40 ]. Finally, RBCs represent approximately the 70% of the total cell body counting [ 41 ], thus it is important to know more about how their metabolism is affected by T2D.…”

Physiological and pathophysiological significance of erythrocyte senescence, density and deformability: Important but unnoticed trinity

“…Less deformable erythrocytes subpopulation is easy to suffer the mechanical stress in microvascular perfusion, which in turn elevates [Ca 2+ ] i leading to further impairment of deformability [59,60]. Therefore, it is not surprising that impairment of deformability is proportional to HbA1c [49,61], because HbA1c reduces the availability of NO, which regulates the cellular deformability [62,63].…”

Raman Spectroscopy of Hemoglobin and Dielectrophoresis of Erythrocytes in the Diagnosis of the Resistant Arterial Hypertension

“…It has been suggested that there should be a unique mechanism for controlling the resistance of pulmonary vessels, according to which the ATP release from the erythrocytes occurs in response to their mechanical deformation, causing stimulation of the synthesis of a NO vasodilator [33].…”