Rezende Flávia, Malacarne Pedro Felipe, Müller Niklas, Rathkolb Birgit, Hrabě de Angelis Martin, Schröder Katrin, P Brandes Ralf
Institute for Cardiovascular Physiology, Goethe University, Theodor-Stern Kai 7, 60590 Frankfurt, Germany.
German Center of Cardiovascular Research (DZHK), Partner Site Rhein Main, 60590 Frankfurt, Germany.
Antioxidants (Basel). 2021 Jul 10;10(7):1103. doi: 10.3390/antiox10071103.
The NADPH oxidase Nox4 is a hydrogen peroxide (HO)-producing enzyme, with the highest expression in the kidney. As the kidney is involved in volume and blood pressure control through sodium handling, we set out to determine the impact of a low sodium diet on these parameters in WT and Nox4-/- mice. Nox4 expression in the murine kidney was restricted to the proximal tubule. Nevertheless, low-sodium-induced weight loss and sodium sparing function was similar in WT and Nox4-/- mice, disputing an important function of renal Nox4 in sodium handling. In contrast, a low sodium diet resulted in a reduction in systolic blood pressure in Nox4-/- as compared to WT mice. This was associated with a selectively lower pressure to heart-rate ratio, as well as heart to body weight ratio. In general, a low sodium diet leads to activation of sympathetic tone and the renin angiotensin system, which subsequently increases peripheral resistance. Our observations suggest that the control by this system is attenuated in Nox4-/- mice, resulting in lower blood pressure in response to low sodium.
烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶Nox4是一种产生过氧化氢（H₂O₂）的酶，在肾脏中表达量最高。由于肾脏通过处理钠来参与调节血容量和血压，我们着手确定低钠饮食对野生型（WT）和Nox4基因敲除（Nox4-/-）小鼠这些参数的影响。Nox4在小鼠肾脏中的表达局限于近端小管。然而，低钠诱导的体重减轻和钠保留功能在WT和Nox4-/-小鼠中相似，这对肾脏Nox4在处理钠方面的重要功能提出了质疑。相比之下，与WT小鼠相比，低钠饮食导致Nox4-/-小鼠的收缩压降低。这与选择性较低的压力心率比以及心脏体重比有关。一般来说，低钠饮食会导致交感神经张力和肾素血管紧张素系统激活，进而增加外周阻力。我们的观察结果表明，该系统在Nox4-/-小鼠中的控制作用减弱，导致对低钠的反应血压降低。
