Effects of acute kidney dysfunction on hypothalamic arginine vasopressin synthesis in transgenic rats
Acute loss of kidney function is a critical internal stressor. Arginine vasopressin (AVP) present in the parvocellular division of the paraventricular nucleus (PVN) plays a key role in the regulation of stress responses. However, hypothalamic AVP dynamics during acute kidney dysfunction remain unclear. In this study, we investigated the effects of bilateral nephrectomy on AVP, using a transgenic rat line that expressed the AVP-enhanced green fluorescent protein (eGFP). The eGFP fluorescent intensities in the PVN were dramatically increased after bilateral nephrectomy. The mRNA levels of eGFP, AVP, and corticotrophin-releasing hormone in the PVN were dramatically increased after bilateral nephrectomy. Bilateral nephrectomy also increased the levels of Fos-like immunoreactive cells in brainstem neurons. These results indicate that bilateral nephrectomy upregulates the AVP-eGFP synthesis. Further studies are needed to identify the neural and/or humoral factors that activate AVP synthesis and regulate neuronal circuits during acute kidney dysfunction.
KeywordsVasopressin Transgenic rat In situ hybridization Hypothalamus Bilateral nephrectomy
We express our appreciation to Ms. Yuki Nonaka for her technical assistance.
Conception or design of the work; HU, RS, TM, MT, YO, YU. Acquisition, analysis, or interpretation of data for the work; HU, KS, YA, KT, HN, KN, SS, YM, RS, MY, TM. Drafting the work or revising it critically for important intellectual content; HU, RS, KS, YA, KT, HN, KN, SS, YM, RS, MY, TM, MT, YO, YU. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated.
This paper was supported by a Grant-in-Aid for Scientific Research (B) (No. 17H04027), (C) (No. 17K08582), and Young Scientist (B) (No. 17K15575) from the Japan Society for the Promotion of Science (JSPS).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures in this study were performed in accordance with the guidelines on the use and care of the laboratory animals as set out care by the Physiological Society of Japan and under control of the Ethics Committee of Animal Care and Experimentation, University of Occupational and Environmental Health (Fukuoka, Japan).
- 1.Ueno H, Yoshimura M, Tanaka K et al (2018) Up-regulation of hypothalamic arginine vasopressin by peripherally administered furosemide in transgenic rats expressing arginine vasopressin-enhanced green fluorescent protein. J Neuroendocrinol 30:1–16. https://doi.org/10.1111/jne.12603 CrossRefGoogle Scholar
- 9.Fujio T, Fujihara H, Shibata M et al (2006) Exaggerated response of arginine vasopressin-enhanced green fluorescent protein fusion gene to salt loading without disturbance of body fluid homeostasis in rats. J Neuroendocrinol 18:776–785. https://doi.org/10.1111/j.1365-2826.2006.01476.x CrossRefGoogle Scholar
- 10.Ueta Y, Fujihara H, Serino R et al (2005) Transgenic expression of enhanced green fluorescent protein enables direct visualization for physiological studies of vasopressin neurons and isolated nerve terminals of the rat. Endocrinology 146:406–413. https://doi.org/10.1210/en.2004-0830 CrossRefGoogle Scholar
- 12.Dos Santos Moreira MC, Naves LM, Marques SM et al (2017) Neuronal circuits involved in osmotic challenges. Physiol Res 8408:411–423Google Scholar
- 13.Cruz JC, Bonagamba LGH, Machado BH et al (2008) Intermittent activation of peripheral chemoreceptors in awake rats induces Fos expression in rostral ventrolateral medulla–projecting neurons in the paraventricular nucleus of the hypothalamus. Neuroscience 157:463–472. https://doi.org/10.1016/j.neuroscience.2008.08.070 CrossRefGoogle Scholar
- 15.Motojima Y, Matsuura T, Yoshimura M et al (2017) Comparison of the induction of c-fos-eGFP and Fos protein in the rat spinal cord and hypothalamus resulting from subcutaneous capsaicin or formalin injection. Neuroscience 356:64–77. https://doi.org/10.1016/j.neuroscience.2017.05.015 CrossRefGoogle Scholar
- 16.Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates. Elsevier Academic Press, AmsterdamGoogle Scholar
- 28.Fernandez BE, Dominguez AE (1990) Effects of angiotensin II and bilateral nephrectomy on norepinephrine catabolism in central nervous system. Arch Int Physiol Biochim 98:307–313Google Scholar
- 29.Domínguez AE, Fernández BE, Vidal NA, Martínez Seeber A (1982) Angiotensin II-norepinephrine relationship in the central nervous system. Arch Int Physiol Biochim 90:269–275Google Scholar
- 30.Plotsky PM (1987) Facilitation of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation after activation of catecholaminergic pathways or central norepinephrine injection. Endocrinology 121:924–930. https://doi.org/10.1210/endo-121-3-924 CrossRefGoogle Scholar
- 37.Oshima N, Onimaru H, Matsubara H et al (2015) Uric acid, indoxyl sulfate, and methylguanidine activate bulbospinal neurons in the RVLM via their specific transporters and by producing oxidative stress. Neuroscience 304:133–145. https://doi.org/10.1016/j.neuroscience.2015.07.055 CrossRefGoogle Scholar
- 39.Domínguez AE, Fernández BE, Vidal NA (1983) The renin–angiotensin system and noradrenaline release in the hypothalamus and medulla oblongata. Rev Esp Fisiol 39:249–252Google Scholar
- 40.Day TA, Ciriello J (1987) Effects of renal receptor activation on neurosecretory vasopressin cells. Am J Physiol 253:R234–R241Google Scholar
- 41.Simon JK, Kasting NW, Ciriello J (1989) Afferent renal nerve effects on plasma vasopressin and oxytocin in conscious rats. Am J Physiol 256:R1240–R1244Google Scholar