Role of NOX2 in the regulation of afferent arteriole responsiveness
Role of NOX2 in the regulation of afferent arteriole responsiveness
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DOI：
10.1152/ajpregu.90718.2008
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发表时间：
2009-01-01
影响因子：
2.8
通讯作者：
Persson, A. Erik G.
中科院分区：
文献类型：
--
作者：
Carlstrom, Mattias;Lai, En Yin;Persson, A. Erik G.
Carlstrom M，Lai EY，Ma Z，Patzak A，Brown RD，Pasterson AE. NOX 2在传入小动脉反应性调节中的作用。Am J Physiol Regul Integr Comp Physiol 296：R72-R79，2009。首次发表于2008年11月5日; doi：10.1152/ajpregu.90718.2008。NADPH氧化酶（NOX）是血管系统中活性氧（ROS）的主要来源，有助于控制肾灌注。在NOX 2（-/-）和野生型小鼠中研究了NOX 2在血压和传入小动脉反应性调节中的作用。与野生型相比，NOX 2（-/-）对ANG II（10（-14）-10（-6）mol/l）的小动脉收缩较弱。N（omega）-硝基-L-精氨酸甲酯（L-NAME; 10（-4）mol/l）处理使NOX 2（-/-）（-18%）的基底直径比野生型（-6%）显著减少，并增强ANG II反应。腺苷（10（-11）-10（-4）mol/l）使野生型的小动脉收缩，但对NOX 2（-/-）无收缩作用。然而，腺苷2型受体的同时抑制诱导血管收缩，这在NOX 2（-/-）中更强。腺苷（10（-8）mol/l）可增强野生型ANG II的反应，但对NOX 2（-/-）无此作用。腺苷的这种增敏作用被夹竹桃麻素消除。慢性ANG II预处理（14天）没有改变NOX 2（-/-）的ANG II反应，但加强了野生型的反应。ANG II预处理增强了NOX 2（-/-）中的L-NAME反应（-33%），但在野生型中没有。同时应用L-NAME和ANG II会导致NOX 2（-/-）（-64%）比野生型（-46%）更强的收缩。两种基因型的基础血压相似，然而，慢性ANG II输注使野生型小鼠的血压升高程度（15 +/- 1%）大于NOX 2（-/-）小鼠（8 +/- 1%）。总之，NOX 2在控制传入小动脉张力中起重要作用，并参与对ANG II和/或腺苷的收缩反应。NOX 2可被升高的ANG II激活，并可能在ANG II诱导的高血压中发挥重要作用。NOX 2衍生的ROS清除一氧化氮，导致随后的一氧化氮缺乏症。
Carlstrom M, Lai EY, Ma Z, Patzak A, Brown RD, Persson AE. Role of NOX2 in the regulation of afferent arteriole responsiveness. Am J Physiol Regul Integr Comp Physiol 296: R72-R79, 2009. First published November 5, 2008; doi:10.1152/ajpregu.90718.2008.-NADPH oxidases (NOX) are the major source of reactive oxygen species (ROS) in the vasculature and contribute to the control of renal perfusion. The role of NOX2 in the regulation of blood pressure and afferent arteriole responsiveness was investigated in NOX2(-/-) and wild-type mice. Arteriole constrictions to ANG II (10(-14)-10(-6) mol/l) were weaker in NOX2(-/-) compared with wild types. N(omega)-nitro-L-arginine methyl ester (L-NAME; 10(-4) mol/l) treatment reduced basal diameters significantly more in NOX2(-/-) (-18%) than in wild types (-6%) and augmented ANG II responses. Adenosine (10(-11)-10(-4) mol/l) constricted arterioles of wild types but not of NOX2(-/-). However, simultaneous inhibition of adenosine type-2 receptors induced vasoconstriction, which was stronger in NOX2(-/-). Adenosine (10(-8) mol/l) enhanced the ANG II response in wild type, but not in NOX2(-/-). This sensitizing effect by adenosine was abolished by apocynin. Chronic ANG II pretreatment (14 days) did not change the ANG II responses in NOX2(-/-), but strengthened the response in wild types. ANG II pretreatment augmented the L-NAME response in NOX2(-/-) (-33%), but not in wild types. Simultaneous application of L-NAME and ANG II caused a stronger constriction in the NOX2(-/-) (-64%) than in wild types (-46%). Basal blood pressures were similar in both genotypes, however, chronic ANG II infusion elevated blood pressure to a greater extent in wild-type (15 +/- 1%) than in NOX2(-/-) (8 +/- 1%) mice. In conclusion, NOX2 plays an important role in the control of afferent arteriole tone and is involved in the contractile responses to ANG II and/or adenosine. NOX2 can be activated by elevated ANG II and may play an important role in ANG II-induced hypertension. NOX2-derived ROS scavenges nitric oxide, causing subsequent nitric oxide-deficiency.