Nitrite enhances RBC hypoxic ATP synthesis and the release of ATP into the vasculature: a new mechanism for nitrite-induced vasodilation
Nitrite enhances RBC hypoxic ATP synthesis and the release of ATP into the vasculature: a new mechanism for nitrite-induced vasodilation
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DOI：
10.1152/ajpheart.01233.2008
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发表时间：
2009-10-01
影响因子：
4.8
通讯作者：
Rifkind, Joseph M.
中科院分区：
文献类型：
--
作者：
Cao, Zeling;Bell, Jeffrey B.;Rifkind, Joseph M.
曹忠，李建军，李建军，李建军。亚硝酸盐促进红细胞缺氧ATP合成和ATP释放到血管：亚硝酸盐诱导血管舒张的新机制。[J]中国生物医学工程学报，2009,31(2):444 - 444。首次发表于2009年8月21日；doi: 10.1152 / ajpheart.01233.2008。-缺氧红细胞（rbc）在亚硝酸盐还原过程中产生的一氧化氮（NO）在调节血管扩张中的作用已经被提出。然而，目前还没有令人满意的解释，这些一氧化氮是如何从红细胞中释放出来的，而不首先与细胞中的大量氧化血红蛋白和脱氧血红蛋白发生反应。在这项研究中，我们描述了一种亚硝酸盐诱导红细胞血管扩张的机制，该机制不需要从细胞中释放NO。相反，我们发现亚硝酸盐增强了红细胞的ATP释放，这是已知的通过几种不同的方法产生血管舒张，包括与内皮上的嘌呤能受体相互作用，刺激内皮NO合成酶合成NO。这一机制是通过给大鼠注射亚硝酸盐反应的红细胞来测量血压的降低来建立的。如果内皮NO合成酶被n -omega-硝基- l -精氨酸甲酯（L-NAME）抑制或任何释放的ATP被apyrase降解，则没有观察到血压的下降。亚硝酸盐增强的ATP释放涉及亚硝酸盐修饰的血红蛋白与红细胞膜的结合增加，从而取代膜上的糖酵解酶，从而形成从红细胞释放的ATP池。因此，这些结果为解释亚硝酸盐诱导的血管舒张提供了新的机制。
Cao Z, Bell JB, Mohanty JG, Nagababu E, Rifkind JM. Nitrite enhances RBC hypoxic ATP synthesis and the release of ATP into the vasculature: a new mechanism for nitrite-induced vasodilation. Am J Physiol Heart Circ Physiol 297: H1494-H1503, 2009. First published August 21, 2009; doi: 10.1152/ajpheart.01233.2008.-A role for nitric oxide (NO) produced during the reduction of nitrite by deoxygenated red blood cells (RBCs) in regulating vascular dilation has been proposed. It has not, however, been satisfactorily explained how this NO is released from the RBC without first reacting with the large pools of oxyhemoglobin and deoxyhemoglobin in the cell. In this study, we have delineated a mechanism for nitrite-induced RBC vasodilation that does not require that NO be released from the cell. Instead, we show that nitrite enhances the ATP release from RBCs, which is known to produce vasodilation by several different methods including the interaction with purinergic receptors on the endothelium that stimulate the synthesis of NO by endothelial NO synthase. This mechanism was established in vivo by measuring the decrease in blood pressure when injecting nitrite-reacted RBCs into rats. The observed decrease in blood pressure was not observed if endothelial NO synthase was inhibited by N-omega-nitro-L-arginine methyl ester (L-NAME) or when any released ATP was degraded by apyrase. The nitrite-enhanced ATP release was shown to involve an increased binding of nitrite-modified hemoglobin to the RBC membrane that displaces glycolytic enzymes from the membrane, resulting in the formation of a pool of ATP that is released from the RBC. These results thus provide a new mechanism to explain nitrite-induced vasodilation.