Red blood cell nitric oxide as an endocrine vasoregulator - A potential role in congestive heart failure
Red blood cell nitric oxide as an endocrine vasoregulator - A potential role in congestive heart failure
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DOI：
10.1161/01.cir.0000124450.07016.1d
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发表时间：
2004-03-23
期刊：
影响因子：
37.8
通讯作者：
James, P
中科院分区：
文献类型：
--
作者：
Datta, B;Tufnell-Barrett, T;James, P
背景-一氧化氮（NO）的呼吸循环涉及肺氧合过程中NO和血红蛋白之间血管活性代谢产物的形成。我们研究了这些代谢产物在缺氧组织中的作用，在体外和体内的健康受试者和充血性心力衰竭（CHF）的患者。方法和结果-我们研究了红细胞（RBC）的能力，以扩张preconstricted主动脉环下各种O-2张力。红细胞在缺氧时诱导环磷酸鸟苷依赖性血管舒张（1%O-2时为35 +/-4%，95%O-2时为4.7 +/-1.6%，P < 0.05）. RBC在缺氧时引起的舒张与S-亚硝基血红蛋白（SNO-Hb）（R-2 = 0.88）相关，但与铁亚硝基血红蛋白（HbFeNO）含量无关。红细胞的弛豫反应进行了比较，S-亚硝基谷胱甘肽在一系列的O-2张力。在1%和2%O-2条件下，红细胞诱发的舒张倍数显著高于95%条件下诱发的舒张倍数（P < 0.05），这与缺氧性血管舒张的变构机制一致。我们还测量了健康对照受试者和CHF患者的NO代谢产物的跨肺梯度。在CHF患者而非对照组中，SNO-Hb水平从0.00293 +/- 0.00089增加至0.00585 +/- 0.00137 mol NO/mol血红蛋白四聚体（P = 0.005），而HbFeNO从0.00361 +/- 0.00109降低到0.00081 +/- 0.00040 mol NO/mol血红蛋白四聚体（P = 0.03），因为血红蛋白在肺循环中被氧合。这些代谢物梯度与血红蛋白O-2饱和度梯度（P < 0.05）和心脏指数（P < 0.05）呈负相关，CHF患者和对照subjects.Conclusions -我们证实，RBC结合NO介导缺氧血管舒张在体外。血红蛋白结合的NO的跨肺梯度在CHF患者中是明显的，并且与心脏指数呈负相关。血红蛋白可以通过变构机制将NO生物活性转运和释放到组织缺氧区域或在外周氧提取增加期间。
Background - A respiratory cycle for nitric oxide ( NO) would involve the formation of vasoactive metabolites between NO and hemoglobin during pulmonary oxygenation. We investigated the role of these metabolites in hypoxic tissue in vitro and in vivo in healthy subjects and patients with congestive heart failure (CHF).Methods and Results - We investigated the capacity for red blood cells (RBCs) to dilate preconstricted aortic rings under various O-2 tensions. RBCs induced cyclic guanylyl monophosphate - dependent vasorelaxation during hypoxia (35 +/- 4% at 1% O-2, 4.7 +/- 1.6% at 95% O-2; P < 0.05). RBC-induced relaxations during hypoxia correlated with S-nitrosohemoglobin (SNO-Hb) (R-2 = 0.88) but not iron nitrosylhemoglobin (HbFeNO) content. Relaxation responses for RBCs were compared with S-nitrosoglutathione across a range of O-2 tensions. The fold increases in relaxation evoked by RBCs were significantly greater at 1% and 2% O-2 compared with relaxations induced at 95% (P < 0.05), consistent with an allosteric mechanism of hypoxic vasodilation. We also measured transpulmonary gradients of NO metabolites in healthy control subjects and in patients with CHF. In CHF patients but not control subjects, levels of SNO-Hb increase from 0.00293 +/- 0.00089 to 0.00585 +/- 0.00137 mol NO/mol hemoglobin tetramer (P = 0.005), whereas HbFeNO decreases from 0.00361 +/- 0.00109 to 0.00081 +/- 0.00040 mol NO/mol hemoglobin tetramer (P = 0.03) as hemoglobin is oxygenated in the pulmonary circulation. These metabolite gradients correlated with the hemoglobin O-2 saturation gradient (P < 0.05) and inversely with cardiac index (P < 0.05) for both CHF patients and control subjects.Conclusions - We confirm that RBC-bound NO mediates hypoxic vasodilation in vitro. Transpulmonary gradients of hemoglobin-bound NO are evident in CHF patients and are inversely dependent on cardiac index. Hemoglobin may transport and release NO bioactivity to areas of tissue hypoxia or during increased peripheral oxygen extraction via an allosteric mechanism.