Endogenous angiotensin II-induced p44/42 mitogen-activated protein kinase activation mediates sodium appetite but not thirst or neurohypophysial secretion in male rats.
Endogenous angiotensin II-induced p44/42 mitogen-activated protein kinase activation mediates sodium appetite but not thirst or neurohypophysial secretion in male rats.
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内源性血管紧张素II诱导的P44/42促丝分裂原激活的蛋白激酶激活介导雄性大鼠的钠食欲，而不是口渴或神经型物理分泌。
DOI：
10.1111/j.1365-2826.2012.02376.x
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发表时间：
2013-02
影响因子：
3.2
通讯作者：
Flanagan-Cato LM
中科院分区：
文献类型：
--
作者：
Felgendreger LA;Fluharty SJ;Yee DK;Flanagan-Cato LM
肾素-血管紧张素-醛固酮系统对体液平衡有重要作用，这种内分泌系统的异常与某些形式的高血压有关。肽激素血管紧张素II（AngII）通过作用于外周和脑靶点来调节水矿物质稳态和血压。在大脑中，AngII与血管紧张素1型受体（AT 1 R）结合，刺激口渴、钠食欲以及精氨酸加压素（AVP）和催产素（OT）分泌。本工作使用了内源性血管紧张素II的实验模型，研究p44/42丝裂原活化蛋白激酶（MAPK）作为介导这些反应的信号传导机制的作用。动物给予联合治疗的呋塞米和低剂量的巯甲丙脯酸（furo/cap），利尿剂和血管紧张素转换酶抑制剂，分别提高内源性血管紧张素II水平在大脑中。Furo/cap在表达AT 1 R的关键脑区诱导p44/42 MAPK活化，并且该作用在集中施用的AT 1 R拮抗剂（厄贝沙坦）或p44/42 MAPK抑制剂（U 0126）中降低。此外，furo/cap治疗引起水和钠的摄入，厄贝沙坦显着减少这两种行为。中枢注射U 0126可显著降低furo/cap诱导的钠摄入量，但对水摄入量无影响。此外，p44/42 MAPK信号传导对于furo/cap或外源性AngII诱导的AVP或OT释放不是必需的。总之，这些结果表明，p44/42 MAPK是所需的血管紧张素II诱导的钠食欲，但不口渴或神经垂体分泌。这一结果可能有助于发现p44/42 MAPK更特异的下游靶点，以抑制钠食欲，已知钠食欲会加剧高血压，同时保持口渴和神经垂体激素分泌不受干扰。
The renin-angiotensin-aldosterone system makes a critical contribution to body fluid homeostasis, and abnormalities in this endocrine system have been implicated in certain forms of hypertension. The peptide hormone angiotensin II (AngII) regulates hydromineral homeostasis and blood pressure by acting on both peripheral and brain targets. In the brain, AngII binds to the angiotensin type 1 receptor (AT1R) to stimulate thirst, sodium appetite and both arginine vasopressin (AVP) and oxytocin (OT) secretion. The present work used an experimental model of endogenous AngII to examine the role of p44/42 mitogen-activated protein kinase (MAPK) as a signalling mechanism to mediate these responses. Animals were given a combined treatment of furosemide and a low dose of captopril (furo/cap), a diuretic and an angiotensin converting enzyme inhibitor, respectively, to elevate endogenous AngII levels in the brain. Furo/cap induced p44/42 MAPK activation in key brain areas that express AT1R, and this effect was reduced with either a centrally administered AT1R antagonist (irbesartan) or a p44/42 MAPK inhibitor (U0126). Additionally, furo/cap treatment elicited water and sodium intake, and irbesartan markedly reduced both of these behaviors. Central injection of U0126markedly attenuated furo/cap-induced sodium intake but not water intake. Furthermore, p44/42 MAPK signalling was not necessary for either furo/cap- or exogenous AngII-induced AVP or OT release. Taken together, these results indicate that p44/42 MAPK is required for AngII-induced sodium appetite, but not thirst or neurohypophysial secretion. This result may allow for discovery of more specific downstream targets of p44/42 MAPK to curb sodium appetite, known to exacerbate hypertension, while leaving thirst and neurohypophysial hormone secretion undisturbed.
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影响因子：
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