Inhibition of Nitric Oxide Synthase 1 Induces Salt-Sensitive Hypertension in Nitric Oxide Synthase 1α Knockout and Wild-Type Mice.
Inhibition of Nitric Oxide Synthase 1 Induces Salt-Sensitive Hypertension in Nitric Oxide Synthase 1α Knockout and Wild-Type Mice.
复制标题
一氧化氮合酶 1 的抑制可诱导一氧化氮合酶 1alpha 敲除小鼠和野生型小鼠的盐敏感性高血压。
DOI：
10.1161/hypertensionaha.115.07032
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Liu R
中科院分区：
文献类型：
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作者：
Wang X;Chandrashekar K;Wang L;Lai EY;Wei J;Zhang G;Wang S;Zhang J;Juncos LA;Liu R
我们最近发现，致密斑中表达的神经元型一氧化氮合酶（NOS 1）的α、β和γ剪接变体和NOS 1 β占NO产生的大部分。我们还证明了特异性地从致密斑缺失NOS 1的小鼠发展成盐敏感性高血压。然而，全球NOS 1 KO菌株既不高血压也不盐敏感。这个全球性的NOS 1 KO菌株实际上是一个NOS 1 αKO模型。因此，我们假设在NOS 1 αKO小鼠中抑制NOS 1 β可诱导盐敏感性高血压。将NOS 1 αKO和C57 BL/6 WT小鼠植入遥测发射器，并分为7-硝基吲唑（7-NI）（10 mg/kg/天）给药组和非给药组。所有小鼠均饲喂正常盐（0.4%NaCl）饮食5天，然后饲喂高盐饮食（4%NaCl）。在用7-NI处理的WT和NOS 1 αKO小鼠中，致密斑产生的NO被抑制超过90%。在NOS 1 αKO和WT小鼠中，清醒小鼠的GFR在高盐饮食后增加约40%。在对急性容量扩张的反应中，用7-NI处理的WT和KO小鼠中的GFR、利尿剂和利钠剂反应显著减弱。平均动脉压在喂食高盐饮食的小鼠中没有显著变化，但在用7-NI处理的NOS 1 αKO和WT小鼠中相似地增加了约15 mmHg。我们的结论是，NOS 1 β，而不是NOS 1 α起着重要的作用，在控制钠排泄和血流动力学响应于急性或慢性盐负荷。
We recently shown that α, β, and γ splice variants of neuronal nitric oxide synthase (NOS1) expressed in the macula densa and NOS1β accounts for most of the NO generation. We have also demonstrated that the mice with deletion of NOS1 specifically from the macula densa developed salt-sensitive hypertension. However, the global NOS1KO strain is not hypertensive nor salt-sensitive. This global NOS1KO strain is actually a NOS1αKO model. Consequently, we hypothesized that inhibition of NOS1β in NOS1αKO mice induces salt-sensitive hypertension. NOS1αKO and C57BL/6 WT mice were implanted with telemetry transmitters and divided into 7-nitroindazole (7-NI) (10mg/kg/day)-treated and non-treated groups. All of the mice were fed a normal salt (0.4% NaCl) diet for 5 days, followed by a high salt diet (4%NaCl). NO generation by the macula densa was inhibited by over 90% in WT and NOS1αKO mice treated with 7-NI. GFR in conscious mice was increased by about 40% following a high salt diet in both NOS1αKO and WT mice. In response to acute volume expansion, GFR, diuretic and natriuretic response were significantly blunted in the WT and KO mice treated with 7-NI. Mean arterial pressure had no significant changes in mice fed a high salt diet, but increased about 15 mmHg similarly in NOS1αKO and WT mice treated with 7-NI. We conclude that NOS1β, but not NOS1α plays an important role in control of sodium excretion and hemodynamics in response to either an acute or a chronic salt loading.