Role of the b93cys, ATP and adenosine in red cell dependent hypoxic vasorelaxation

International Journal of Physiology, Pathophysiology and Pharmacology

Jaideep Honavar¹  Tim Townes¹  Rakesh P Patel¹  Chiao-Wang Sun¹  Yanping Liu¹ 

关键词: Hemoglobin;    nitric oxide;    vasorelaxation;    thiol;    hypoxia;    blood flow;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

Two of the proposed mechanisms by which red blood cells (RBC) mediate hypoxic vasorelaxation by coupling hemoglobin deoxygenation to the activation of nitric oxide signaling involve ATP-release from RBC and S-nitrosohemoglobin (b93C(SNO)Hb) dependent bioactivity. However, different studies have reached opposite conclusions regarding the aforementioned mechanisms. Using isolated vessels, hypoxic vasorelaxation induced by human, C57BL/6 or mouse RBC which exclusively express either native human hemoglobin (HbC93) or human hemoglobin in which the conserved b93cys was replaced with Ala (HbC93A) were compared. All RBCs stimulated hypoxic vasodilation to similar extents suggesting the b93cys is not required for this RBC-mediated function. Hypoxic vasorelaxation was inhibited by co-incubation of ATP-pathway blockers including L-NAME (eNOS inhibitor) and Apyrase. Moreover, we tested if modulation of adenosine-dependent signaling affected RBC-dependent vasorelaxation using pan- or subtype specific adenosine receptor blockers, or adenosine deaminase (ADA). Interestingly, ADA and adenosine A₂ receptor blockade, but not A₁ receptor blockade, inhibited HbC93, HbC93A dependent hypoxic vasorelaxation. Equivalent results were obtained with human RBC. These data suggest that using isolated vessels, RBC do not require the presence of the b93cys to elicit hypoxic vasorelaxation and mediate this response via ATP- and a novel adenosine-dependent mechanism.

【 授权许可】

Unknown