Anaemia occurs frequently in patients with heart failure and its current treatment lacks clear targets. Emerging evidence suggests that erythroid progenitor cell expansion is an integral part of physiological response to anaemia associated with chronic stress. Understanding the underlying mechanism may provide a novel approach to anaemia management. In this study, we aimed to examine a role for nitric oxide (NO) in the regulation of bone marrow erythroid progenitor response to chronic stress. For this purpose, adult male mice were subjected to 2 h daily restraint stress for 7 or 14 consecutive days. The role of NO was assessed by subcutaneous injection with NG-nitro-l-arginine methyl ester, 30 min prior to each restraint. Chronic exposure to stress resulted in significantly increased number of bone marrow erythroid progenitors, and blockade of NO biosynthesis prior to daily stress completely prevented stress-induced erythroid progenitor cell expansion. Furthermore, chronic stress exposure led to altered expression of neural, endothelial and inducible nitric oxide synthases (NOS) in the bone marrow, both on mRNA and protein level. Decreased expression of neural and endothelial NOS, as well as reduced expression of NF-kappaB/p65 in bone marrow nuclear cell fraction, was accompanied by elevated bone marrow expression of inducible NOS in chronically stressed animals. This is the first study to demonstrate a role for NO in adaptive response of erythroid progenitors to chronic stress. Targeting NO production may be beneficial to improve bone marrow dysfunction and reduced erythroid progenitor cell expansion in chronic heart failure patients.

贫血经常发生在心力衰竭患者中，目前的治疗方法尚缺乏明确的目标。越来越多的证据表明，类红细胞祖细胞扩增是对与慢性应激相关的贫血的生理反应的重要组成部分。了解潜在机制可能为贫血管理提供一种新颖的方法。在这项研究中，我们旨在检查一氧化氮（NO）在调节骨髓红系祖细胞对慢性应激反应中的作用。为此，成年雄性小鼠每天连续2或7天每天受到约束应激。NO的作用是通过皮下注射NG硝基评估升-精氨酸甲酯，每次约束前30分钟。长期暴露于压力下会导致骨髓红系祖细胞的数量显着增加，并且在每日应激之前阻断NO生物合成会完全阻止应激诱导的红系祖细胞的扩张。此外，慢性应激暴露导致mRNA和蛋白质水平的神经，内皮和诱导型一氧化氮合酶（NOS）表达在骨髓中改变。在慢性应激动物中，神经和内皮NOS的表达降低，以及NF-κB/ p65在骨髓核细胞级分中的表达降低，同时伴随着诱导型NOS的骨髓表达升高。这是第一个证明NO在红系祖细胞对慢性应激的适应性反应中的作用的研究。