Abstract
GP.Mur, a red blood cell (RBC) hybrid protein encoded by glycophorin B-A-B, increases expression of erythroid band 3 (Anion Exchanger-1, SLC4A1). GP.Mur is extremely rare but has a prevalence of 1–10% in regions of Southeast Asia. We unexpectedly found slightly higher blood pressure (BP) among healthy Taiwanese adults with GP.Mur. Since band 3 has been suggested to interact with hemoglobin (Hb) to modulate nitric oxide (NO)-dependent hypoxic vasodilation during the respiratory cycle, we hypothesized that GP.Mur red cells could exert differentiable effects on vascular tone. Here we recruited GP.Mur-positive and GP.Mur-negative elite male college athletes, as well as age-matched, GP.Mur-negative non-athletes, for NO-dependent flow-mediated dilation (FMD) and NO-independent dilation (NID). The subjects were also tested for plasma nitrite and nitrate before and after arterial occlusion in FMD. GP.Mur+ and non-GP.Mur athletes exhibited similar heart rates and blood pressure, but GP.Mur+ athletes showed significantly lower FMD (4.8 ± 2.4%) than non-GP.Mur athletes (6.5 ± 2.1%). NO-independent vasodilation was not affected by GP.Mur. As Hb controls intravascular NO bioavailability, we examined the effect of Hb on limiting FMD and found it to be significantly stronger in GP.Mur+ subjects. Biochemically, plasma nitrite levels were directly proportional to individual band 3 expression on the red cell membrane. The increase of plasma nitrite triggered by arterial occlusion also showed small dependency on band 3 levels in non-GP.Mur subjects. By the GP.Mur comparative study, we unveiled comodulation of NO-dependent vasodilation by band 3 and Hb, and verified the long-pending role of erythroid band 3 in this process.
Highlights
Hemoglobin (Hb) modulates vascular tone by controlling nitric oxide bioavailability in the blood stream
The interaction between band 3 and deoxygenated Hb in the submembranous domain has been suggested to assist the transport of nitric oxide (NO) metabolites across the red cell membrane by unclear means [7,8,9,10]
To probe into the potential impacts of GP.Mur/band 3 on NOdependent reactive hyperemia in a uniform cohort, this study recruited primarily male elite college athletes from top-ranking Taiwan sports universities where the prevalence of GP.Mur is much higher than the general Taiwanese population
Summary
Hemoglobin (Hb) modulates vascular tone by controlling nitric oxide bioavailability in the blood stream. The chemical reaction between Hb and NO metabolites is coupled with the dynamics of O2 saturation and desaturation of Hb [1,2,3,4,5]. While intraerythrocytic Hb is considered the most powerful NO scavenger in human body, its effect on NO-associated vasodilation is limited by the RBC membrane [6]. Hb-mediated NO bioavailability has been proposed to require band 3, the main anion transporter on RBCs. The interaction between band 3 and deoxygenated Hb in the submembranous domain has been suggested to assist the transport of NO metabolites (e.g., nitrite and SNO) across the red cell membrane by unclear means [7,8,9,10]. The role of band 3 in RBC-dependent NOx processing and hypoxic vasodilation is enigmatic
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