Erythrocyte Nitric Oxide

Abstract

Nitric oxide (NO) is a vasoactive molecule that, by stimulated and functional vascular endothelial cells, is released to the lumen of the vessel and into the surrounding smooth muscle cells. Once in the lumen, NO is captured by red blood cells and scavenged inside through hemoglobin and derived as NO metabolites. The delivery ability of erythrocytes allowing the NO efflux also occurs. Manipulation of NO levels inside the erythrocyte through different external (acetylcholine, acetylcholinesterase inhibitors, fibrinogen and CD47 4N1K peptide) and internal (redox and protein phosphorylation levels) stimuli will be described. The values of NO efflux from the erythrocytes and its association with the data quantified in the hemorheology properties and in clinical parameters obtained from patients with vascular diseases will also be present. The in vivo animal experimental studies highlighting the ability of NO efflux (delivered) from the erythrocytes where is scavenged and its influence in inflammatory and hemorheological responses will be addressed. So, the aim of this chapter is to present the knowledge obtained about the NO signal transduction mechanism in erythrocytes and the association between erythrocyte availability in NO with clinical biomarkers obtained in inflammatory vascular diseases. A final question is raised-namely, could NO be considered a hemorheological parameter?

Understanding Red Blood Cell Rheology in Sepsis and its Role in Clinical Practice. From Biomolecular Aspects to Possible Therapeutic Interventions

“…In sepsis, RBC NO and nitrosothiols production and release can be increased via band 3 phosphorylation and NO interaction with reactive species resulted from hemoglobin autooxidation [69,99]. These mechanisms were described in more detail earlier (see Band 3 phosphorylation).…”

“…Phosphorylation of band 3 protein is of importance in sepsis because it plays a significant role in intraerythrocytic metabolic alterations of glycolysis and oxygen delivery, and by extension influences RBC deformability (through several mechanisms) and RBC NO release behaviour [9,69,70,71,72]. Band 3 protein phosphorylation and dephosphorylation was reported in both in vitro [70,71,72] and in vivo [72] studies, using tyrosine kinase inhibitors.…”

“…ATP will bind to the P2Y receptors, inducing NO synthesis, which will further alter RBC deformability [81]. Moreover, glycolytic pathway stimulation, decreased levels of intraerythrocytic reductants (altered NO-glutathione interaction), band 3 phosphorylation and dephosphorylation influences intraerythrocitic NO chemical reactions and modifies its bioavailability and release from RBCs [69]. Finally, band 3 protein phoshphorylation in presence of high fibrinogen levels determines a higher NO release from RBCs [82,83].…”

“…NO affinity for hemoglobin is high [99] (increased affinity for thiol groups or for the iron ion), but NO binding at Hb is dependent on oxygen partial pressure [69,99]. At arterial oxygen partial pressure (high-pressure, PaO2) NO and oxy-Hb form S-nitrosohemoglo-bin (SNO-HBO2) through NO binding at the thiol group of cysteine β93 [69], but at low oxygen partial pressures (as it happens in sepsis), NO interacts with the iron ion binding to it and resulting in nitrosylhemoglobin molecules formation [165]. In 1996, Jubelin et al [166] suggested that erythrocytes can be able to produce NO.…”

“…Simplyfied, it's important to keep in mind that NO is released from RBCs in conditions of hypoxia, which in sepsis has a significant impact on erythrocyte rheology and microcirculation [81]. NO role in RBC deformability seen in sepsis was reported in several studies [22,27,69,81,153,[169][170][171][172][173]. Petrov et al [174,175] reported presence of soluble guanylate cyclase inside erythrocytes and it is known that NO action is modulated by guanylate cyclase (sGC).…”