Carlström Mattias, Lai En Yin, Ma Zufu, Patzak Andreas, Brown Russell D, Persson A Erik G
Dept. of Medical Cell Biology, Biomedical Centre, Box 571, SE-75123 Uppsala, Sweden.
Am J Physiol Regul Integr Comp Physiol. 2009 Jan;296(1):R72-9. doi: 10.1152/ajpregu.90718.2008. Epub 2008 Nov 5.
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.
烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NOX）是血管系统中活性氧（ROS）的主要来源，并参与肾灌注的调控。在NOX2基因敲除小鼠和野生型小鼠中研究了NOX2在血压调节和入球小动脉反应性中的作用。与野生型相比，NOX2基因敲除小鼠对血管紧张素II（ANG II，10⁻¹⁴ - 10⁻⁶ mol/L）的小动脉收缩作用较弱。用N⁻硝基⁻L⁻精氨酸甲酯（L⁻NAME，10⁻⁴ mol/L）处理后，NOX2基因敲除小鼠的基础管径显著减小（-18%），大于野生型小鼠（-6%），并且增强了对ANG II的反应。腺苷（10⁻¹¹ - 10⁻⁴ mol/L）使野生型小鼠的小动脉收缩，但对NOX2基因敲除小鼠无效。然而，同时抑制腺苷2型受体可诱导血管收缩，在NOX2基因敲除小鼠中更强。腺苷（10⁻⁸ mol/L）增强了野生型小鼠对ANG II的反应，但对NOX2基因敲除小鼠无效。腺苷的这种致敏作用被阿朴吗啡消除。慢性ANG II预处理（14天）未改变NOX2基因敲除小鼠对ANG II的反应，但增强了野生型小鼠的反应。ANG II预处理增强了NOX2基因敲除小鼠对L⁻NAME的反应（-33%），但对野生型小鼠无效。同时应用L⁻NAME和ANG II导致NOX2基因敲除小鼠的收缩作用更强（-64%），大于野生型小鼠（-46%）。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幅度更大（15±1%），大于NOX2基因敲除小鼠（8±1%）。总之，NOX2在入球小动脉张力控制中起重要作用，并参与对ANG II和/或腺苷的收缩反应。NOX2可被升高的ANG II激活，可能在ANG II诱导的高血压中起重要作用。NOX2产生的ROS清除一氧化氮，导致随后的一氧化氮缺乏。
