Upregulation of hypothalamic arginine vasopressin by peripherally administered furosemide in transgenic rats expressing arginine vasopressin-enhanced green fluorescent protein
Upregulation of hypothalamic arginine vasopressin by peripherally administered furosemide in transgenic rats expressing arginine vasopressin-enhanced green fluorescent protein
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表达精氨酸加压素增强绿色荧光蛋白的转基因大鼠中外周注射呋塞米对下丘脑精氨酸加压素的上调
DOI：
10.1111/jne.12603
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发表时间：
2018
影响因子：
3.2
通讯作者：
Ueta Yoichi
中科院分区：
文献类型：
--
作者：
Ueno Hiromichi;Yoshimura Mitsuhiro;Tanaka Kentaro;Nishimura Haruki;Nishimura Kazuaki;Sonoda Satomi;Motojima Yasuhito;Saito Reiko;Maruyama Takashi;Miyamoto Tetsu;Serino Ryota;Tamura Masahito;Onaka Tatsushi;Otsuji Yutaka;Ueta Yoichi
速尿在世界范围内被用作利尿剂，它抑制亨勒氏环中的钠重吸收，导致利尿和利钠。精氨酸加压素(AVP)在下丘脑视上核(SON)、室旁核(PVN)和视交叉上核合成。SON和PVN大细胞神经元AVP的合成受到血浆渗透压和血容量的生理调节，并通过增加集合管对水的重吸收来促进水的动态平衡。外周给药速尿后的中枢AVP动力学尚不清楚。在本研究中，我们研究了ip.速尿(20 mg/kg−-1)对大鼠下丘脑加压素作用的实验研究IP地址。在本研究中，给药速尿不影响血浆渗透压；然而，与对照组相比，给药后室旁核SON和大细胞分裂(MPVN)中的EGFP显著增加。免疫组织化学分析显示，腹腔注射后90min，SON和mPVN的EGFP阳性神经元内有Fos样免疫反应(-IR)。给予速尿和AVP后，其异核RNA和GFP基因表达水平显著升高。在视交叉上AVP神经元中，未观察到速尿引起的上述变化。此外，腹腔注射呋塞米后，血管板层终器、视前正中核、穹隆下器、蓝斑、孤束核和延髓头端腹外侧区Fos-IR显著增加。速尿的用法。总之，我们能够利用AVP-EGFP转基因大鼠来可视化和定量评估外周注射速尿后AVP-EGFP的合成和神经元的激活。本研究的结果可能提供新的见解，并有助于阐明速尿诱导体液内稳态的生理机制。
Furosemide, which is used worldwide as a diuretic agent, inhibits sodium reabsorption in Henle's loop, resulting in diuresis and natriuresis. Arginine vasopressin (AVP) is synthesised in the supraoptic nucleus (SON), paraventricular nucleus (PVN) and suprachiasmatic nucleus of the hypothalamus. The synthesis of AVP in the magnocellular neurones of SON and PVN is physiologically regulated by plasma osmolality and blood volume and contributes to water homeostasis by increasing water reabsorption in the collecting duct. Central AVP dynamics after peripheral administration of furosemide remain unclear. In the present study, we investigated the effects of i.p. administration of furosemide (20 mg kg−1) on hypothalamic AVP using transgenic rats expressing AVP‐enhanced green fluorescent protein (eGFP) under the AVP promoter. The i.p. administration of furosemide did not affect plasma osmolality in the present study; however, eGFP in the SON and magnocellular divisions of the PVN (mPVN) was significantly increased after furosemide administration compared to the control. Immunohistochemical analysis revealed Fos‐like immunoreactivity (‐IR) in eGFP‐positive neurones in the SON and mPVN 90 minutes after i.p. administration of furosemide, andAVPheteronuclear RNA andeGFPmRNA levels were significantly increased. These furosemide‐induced changes were not observed in the suprachiasmatic AVP neurones. Furthermore, furosemide induced a remarkable increase in Fos‐IR in the organum vasculosum laminae terminals, median preoptic nucleus, subfornical organ, locus coeruleus, nucleus of the solitary tract and rostral ventrolateral medulla after i.p. administration of furosemide. In conclusion, we were able to visualise and quantitatively evaluate AVP‐eGFP synthesis and neuronal activation after peripheral administration of furosemide using AVP‐eGFP transgenic rats. The results of the present study may provide new insights and help clarify the physiological mechanisms underlying the body fluid homeostasis induced by furosemide.