Role of angiotensin in body fluid homeostasis of mice: effect of losartan on water and NaCl intakes

Abstract

Crews, Emily C., and Neil E. Rowland. Role of angiotensin in body fluid homeostasis of mice: effect of losartan on water and NaCl intakes. Am J Physiol Regul Integr Comp Physiol 288: R638 -R644, 2005. First published November 4, 2004 doi:10.1152/ajpregu. 00525.2004.-It is known that mice injected peripherally with ANG II do not show a drinking response but that cFos immunoreactivity (ir) is induced in brain regions similar to those in rats. We now show in Crl:CD1(ICR) mice that peripheral injection of the ANG II type 1 receptor antagonist losartan was sufficient to prevent this induction of Fos-ir in the subfornical organ (SFO). Injection of ANG II into the lateral cerebral ventricle produced a robust water intake in mice and induced Fos-ir in SFO, as well as in median preoptic (MnPO) and paraventricular (PVN) nuclei. Peripheral injection of losartan blocked this drinking response and prevented the induction of Fos-ir in each of these brain regions. Hypovolemia produced by polyethylene glycol (PEG) produced a robust water intake but no evidence of sodium appetite, and it induced Fos-ir in SFO, MnPO, and PVN. Peripheral injection of losartan did not affect this drinking response. Fos-ir induced by PEG in SFO and MnPO was reduced by treatment with losartan, while that induced in the PVN was further increased by losartan. Sodium depletion with furosemide and low-sodium diet produced a strong sodium appetite and induced Fos-ir in SFO and MnPO. Treatment with losartan completely blocked the sodium appetite, as well as the induction of Fos-ir in these brain regions. These data indicate that endogenous production of ANG II and action at forebrain receptors is critically involved in depletion-related sodium appetite in mice. The absence of an effect of losartan on PEG-induced drinking suggests the critical involvement of other factor(s) such as arterial or venous baroreceptor input, and we discuss how this factor could also explain why peripheral ANG II is not dipsogenic in mice.hypovolemia; sodium depletion; subfornical organ; baroreceptors; Fos immunoreactivity THE RENIN-ANGIOTENSIN CASCADE has important signaling functions in many tissues, including an integrative role in the regulation of hydromineral homeostasis by the brain (4, 5). Most of the studies that have led to this knowledge, especially in regard to neural mechanisms, have been performed in a few strains of rats. Contemporary interest in the use of mouse transgenic models has made it important to understand whether and how this rat-based model applies to mice. In particular, studies from this laboratory (12), as well as others (1, 4, 18), performed over a decade ago suggested that mice of several strains did not use ANG II as a signal molecule in precisely the same way as rats. Most prominent among the findings was that mice drank neither water nor NaCl solution when injected peripherally with ANG II (6, 12, 14, 18).There are two general classes of potential explanations for that finding. The first is that ANG II is not dipsogenic because it does not hav...

Osmoregulatory fluid intake but not hypovolemic thirst is intact in mice lacking angiotensin

“…Similarly, our results show that sodium intake stimulated by PEG-induced hypovolemia in WT mice is also dependent on angiotensin II, either of peripheral or central origin. Contrasting with some earlier studies (7,20,38), we were able to observe increased sodium chloride intake in WT mice following PEG administration. The reasons for this difference are not clear; however, there is one other report of increased intake of NaCl solution (0.15 mol/l) in mice following PEG administration (37).…”

“…These data show that activation of neurons in the SFO and OVLT of WT mice in response to hypovolemia is probably caused by the action of circulating angiotensin II that would increase in the circulation due to hypovolemic stimulation of the renin-angiotensin system by PEG treatment in WT mice, but not in AgtϪ/Ϫ mice. Our data are consistent with observations of Crews and Rowland (7), showing that peripheral administration of the AT 1 receptor antagonist losartan prevents c-fos expression in the SFO and OVLT of PEG-treated C57BL6 mice. By contrast, the number of neurons exhibiting Fos-IR in response to hypovolemia increased in the SON of both AgtϪ/Ϫ and WT mice.…”

The Estrogen-Related Receptor Alpha Upregulates Secretin Expressions in Response to Hypertonicity and Angiotensin II Stimulation

“…In view of a recent study revealing a potential function of ERRα in the renin-angiotensin system (RAS) for osmoregulation [9] and the presence of an ERE-half site in the proximal region of the mouse (from −149 to −144 bp, relative to the start codon), rat and human SCT promoters (Fig. 1A), we initially investigated the in vitro function of ERRs to control the mouse SCT gene in a mouse hypothalamic N-42 cell-line.…”

“…In specific brain regions, both plasma hypertonicity and circulating ANGII are able to stimulate the lamina terminalis, consisting of the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT) and median preoptic nucleus (MnPO), which are critical sites for regulating water homeostasis in rodents [9]–[14]. Not just that we found SCT and SCTR expression in these water regulation sites, we found also that SCT injected into the lateral ventricle of the brain could augment water drinking behavior, as well as VP expression and VP protein release.…”

Effect of sex chromosome complement on sodium appetite and Fos-immunoreactivity induced by sodium depletion

“…The MnPO, together with the SFO and OVLT, form the lamina terminalis (LT), which has been shown to play a major role in many aspects of body fluid homeostasis (39). Furo/LSD treatment in mice induces sodium appetite and increased FOS-ir along the SFO and MnPO compared with basal or control values (18). Moreover, in rats the same sodium depletion treatment also induced an increase in c-fos expression along the LT (3).…”