Erythroid anion transport, nitric oxide, and blood pressure

Kate Hsu

doi:10.3389/fphys.2024.1363987

Erythroid anion transport, nitric oxide, and blood pressure

Front Physiol. 2024 Apr 10:15:1363987. doi: 10.3389/fphys.2024.1363987. eCollection 2024.

Author

Kate Hsu^{1

2

3}

Affiliations

¹ The Laboratory of Immunogenetics, Department of Medical Research, MacKay Memorial Hospital, New Taipei City, Taiwan.
² MacKay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan.
³ Institute of Biomedical Sciences, MacKay Medical College, New Taipei City, Taiwan.

Abstract

Glycophorin A and glycophorin B are structural membrane glycoproteins bound in the band 3 multiprotein complexes on human red blood cells (RBCs). Band 3 is an erythroid-specific anion exchanger (AE1). AE1-mediated HCO₃ ^- transport provides the substrate for the enzyme-catalyzed conversion HCO₃ ^- _(aq) ⇌ CO_2(g), which takes place inside the RBCs. Bicarbonate transport via AE1 supports intravascular acid-base homeostasis and respiratory excretion of CO₂. In the past decade, we conducted several comparative physiology studies on Taiwanese people having the glycophorin variant GPMur RBC type (which accompanies greater AE1 expression). We found that increased anion transport across the erythrocyte membrane not only enhances gas exchange and lung functions but also elevates blood pressure (BP) and reduces nitric oxide (NO)-dependent vasodilation and exhaled NO fraction (FeNO) in healthy individuals with GP.Mur. Notably, in people carrying the GPMur blood type, the BP and NO-dependent, flow-mediated vasodilation (FMD) are both more strongly correlated with individual hemoglobin (Hb) levels. As blood NO and nitrite (NO₂ ^-) are predominantly scavenged by intraerythrocytic Hb, and NO₂ ^- primarily enters RBCs via AE1, could a more monoanion-permeable RBC membrane (i.e., GPMur/increased AE1) enhance NO₂ ^-/NO₃ ^- permeability and Hb scavenging of NO₂ ^- and NO to affect blood pressure? In this perspective, a working model is proposed for the potential role of AE1 in intravascular NO availability, blood pressure, and clinical relevance.

Keywords: GP.Mur (Miltenberger subtype III, Mi.III); band 3 (anion exchanger-1, AE1); blood pressure; dipyridamole; erythrocyte; glycophorin; nitric oxide; vasodilation.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Taiwan Ministry of Science and Technology (MOST 108-2628-B-195-001; 109-2628-B-195-001; 110-2628-B-195-001) and from MacKay Memorial Hospital to KH(MMH 111-26; 112-63; MMH 111-38; MMH 112-128; MMH 113-67).