Low dose L-NAME induces salt sensitivity associated with sustained increased blood volume and sodium-chloride cotransporter activity in rodents.
Low dose L-NAME induces salt sensitivity associated with sustained increased blood volume and sodium-chloride cotransporter activity in rodents.
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低剂量的 L-NAME 会诱导啮齿类动物对盐敏感，并与持续增加的血容量和氯化钠协同转运蛋白活性相关。
DOI：
10.1016/j.kint.2020.05.050
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发表时间：
2020-06
影响因子：
19.6
通讯作者：
Suang Suang Koid
中科院分区：
文献类型：
--
作者：
Conghui Wang;Xiangmei Chen;Sayoko Ogura;Lei Kang;Tatsuo Shimosawa;Beibei Liu;Latapati Reheman;Toshiro Fujita;Nobuhiro Ayuzawa;Alimila Yeerbolati;Yutaka Yatomi;Fumiko Kawakami-Mori;Suang Suang Koid
为了研究血压正常动物模型中盐敏感性的原因，我们用低剂量的一氧化氮合酶抑制剂 L-NAME 治疗大鼠，该抑制剂本身不会升高血压或诱导肾纤维化。高盐饮食在前 24 小时内增加了 L-NAME 治疗和未治疗动物的循环血量。此后，仅 L-NAME 治疗的大鼠血容量持续增加。从接触高盐饮食开始，L-NAME 治疗组的血压就较高。在盐负荷的前 24 小时内，L-NAME 治疗的动物未能表现出血管舒张，并在响应血容量扩张时保持较高的全身血管阻力。高盐饮食 4 周后，L-NAME 治疗组的压力-尿钠排泄曲线斜率变缓。用氢氯噻嗪治疗后观察到尿钠增加，但阿米洛利没有增加，这种变化与磷酸化氯化钠协同转运蛋白（NCC）增加同时观察到。相比之下，在喂食高盐饮食的 L-NAME 治疗的 NCC 缺陷小鼠中没有观察到血压变化。此外，在小鼠远曲小管细胞中证实了 L-NAME 直接诱导的 NCC 激活。血管扩张剂硝普钠下调磷酸化 NCC 表达。 L-NAME 对磷酸化 NCC 的作用被 SPAK 抑制剂 STOCK2S-26016 和超氧化物歧化酶模拟物 TEMPO 阻断，后者也减轻了盐诱导的高血压。这些结果表明，血压正常的啮齿类动物开始出现盐敏感性可能是由于脉管系统反应性低下所致，而维持血压可能会由于低剂量 L-NAME 模型中不适当的 NCC 活性而导致高循环容量。因此，即使一氧化氮的产生轻微受损，对于健康啮齿动物的盐敏感性调节也可能很重要。
To investigate the cause of salt sensitivity in a normotensive animal model, we treated rats with a low-dose of the nitric oxide synthase inhibitor, L-NAME, that does not elevate blood pressure per se or induce kidney fibrosis. A high salt diet increased the circulating blood volume both in L-NAME-treated and nontreated animals for the first 24 hours. Thereafter, the blood volume increase persisted only in the L-NAME-treated rats. Blood pressure was higher in the L-NAME-treated group from the start of high salt diet exposure. Within the first 24 hours of salt loading, the L-NAME treated animals failed to show vasodilation and maintained high systemic vascular resistance in response to blood volume expansion. After four weeks on the high salt diet, the slope of the pressure-natriuresis curve was blunted in the L-NAME-treated group. An increase in natriuresis was observed after treatment with hydrochlorothiazide, but not amiloride, a change observed in parallel with increased phosphorylated sodium-chloride cotransporter (NCC). In contrast, a change in blood pressure was not observed in L-NAME-treated NCC-deficient mice fed a high salt diet. Moreover, direct L-NAME-induced NCC activation was demonstrated in cells of the mouse distal convoluted tubule. The vasodilatator, sodium nitroprusside, downregulated phosphorylated NCC expression. The effect of L-NAME on phosphorylated NCC was blocked by both the SPAK inhibitor STOCK2S-26016 and the superoxide dismutase mimetic TEMPO which also attenuated salt-induced hypertension. These results suggest that the initiation of salt sensitivity in normotensive rodents could be due to hyporeactivity of the vasculature and that maintaining blood pressure could result in a high circulating volume due to inappropriate NCC activity in the low-dose L-NAME model. Thus, even slightly impaired nitric oxide production may be important in salt sensitivity regulation in healthy rodents.
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影响因子：
1.5
作者：
Mishra S;Ingole S;Jain R
通讯作者：
Jain R
影响因子：
13.6
作者：
Giani, Jorge F.;Janjulia, Tea;Gonzalez-Villalobos, Romer A.
通讯作者：
Gonzalez-Villalobos, Romer A.
影响因子：
12.3
作者：
Amaral, Taline A. S.;Ognibene, Dayane T.;Resende, Angela C.
通讯作者：
Resende, Angela C.
影响因子：
--
作者：
GREENE, AS;YU, ZY;COWLEY, AW
通讯作者：
COWLEY, AW
DOI：
--
发表时间：
2009-05
期刊：
Journal of the American Association for Laboratory Animal Science : JAALAS
影响因子：
--
作者：
V. Braga;N. Prabhakar
通讯作者：
V. Braga;N. Prabhakar