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Endothelial Cell Hbα Can Regulate Blood Pressure
Author(s) -
Butcher Joshua,
DeLalio Leon,
Biwer Lauren,
Lang Susan,
Weaver Rachel,
BestCampbell Angela,
Good Miranda,
Isakson Brant
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.789.14
Subject(s) - enos , phenylephrine , nitric oxide , hemoglobin , blood pressure , medicine , endocrinology , endothelium , vasodilation , constriction , chemistry , nitric oxide synthase
We have recently shown that the alpha subunit of hemoglobin (Hbα) is found in endothelial cells (EC) of resistance arteries and that it closely associates with endothelial NO synthase (eNOS) to regulate nitric oxide (NO) diffusion from the EC to smooth muscle cells (SMC) after adrenergic constriction. Hypertensive mouse models have shown significantly increased Hbα/eNOS association, whereas application of a peptide (HbαX) intended to disrupt the interaction and functionally ablate NO‐scavenging significantly decreased Hbα/eNOS association. In order to test this proposed mechanism in humans, we used ~100 µm arterioles from gluteal biopsies and found that hypertensive humans had significantly increased Hbα/eNOS association and constrictive arteries; both the Hbα/eNOS association and hyperconstriction were reversed with HbαX. In addition we used a mouse model that disrupts one of the two alpha globin genes (HBA1 ‐/‐ ). We find that the resistance arteries from HBA1 ‐/‐ response to phenylephrine is severely blunted, but can be restored to litter mate control levels of constriction with administration of L‐NAME. This functional observation was supported by depleted Hbα in endothelium of HBA1 ‐/‐ resistance arteries. HBA1 ‐/‐ mice showed a significant decrease in blood pressure, independent of anemia. Mouse blood transfusion experiments between HBA1 ‐/‐ and C57Bl6 mice have been performed to validate this observation. Taken together, these data provide crucial evidence for the novel concept that Hbα in the EC of resistance arteries can directly regulate blood pressure and could be an important pharmacological target for hypertension.