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Up‐regulation of hypothalamic arginine vasopressin by peripherally administered furosemide in transgenic rats expressing arginine vasopressin‐enhanced green fluorescent protein

H. Ueno,M. Yoshimura,Kentarou Tanaka,H. Nishimura,K. Nishimura,S. Sonoda,Y. Motojima,R. Saito,Takashi Maruyama,T. Miyamoto,R. Serino,M. Tamura,T. Onaka,Yutaka Otsuji,Yoichi Ueta

Published 2018 in Journal of neuroendocrinology

ABSTRACT

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, and AVP heteronuclear RNA and eGFP mRNA 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.

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