Water deprivation upregulates ANG II AT1 binding and mRNA in rat subfornical organ and anterior pituitary

Sanvitto, Gilberto Luiz; Häuser, Walter; Saavedra, Juan M.

doi:10.1152/ajpendo.1997.273.1.e156

Cited by 34 publications

(43 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies in which in situ hybridization and polymerase chain reaction methods were used for the localization and quantification of the mRNA for the AT1-receptor subtypes showed that AT1b receptors were of a lower density and were expressed in brain, testes, adrenal, kidney, and pituitary. 4,7,8,15,18,36 In the rat brain, there is strong evidence for the presence of AT1b mRNA in AP and more controversy regarding its localization in SFO. 4,15,18 The question is whether the mRNA is directly translatable into receptor protein.…”

Section: Discussionmentioning

confidence: 99%

“…To identify the receptor subtypes, 0. 4 14 C to 125 I-Ang II in fmol/mg protein. 26 Different exposure times were used to obtain accurate readings for high, moderate, and low densities of binding according to the linear range of the film.…”

Section: Receptor Autoradiographymentioning

confidence: 99%

“…4 -8 Dehydration in rats produced an increase in Ang type 1 (AT1) receptors in anterior pituitary (AP) and subfornical organ (SFO), with no change noted in the paraventricular nucleus (PVN). 4,5,9 Salt loading caused an increase in SFO and PVN Ang receptors. 8,10 Physiological interactions are also observed, such as Ang-mediated drinking and vasopressin responses, sodium-induced potentiation of the pressor action of Ang, and angiotensinergic modulation of the response to dehydration.…”

mentioning

confidence: 95%

“…In mice, receptor changes were seen after 2 days of dehydration, whereas in rats the earliest time to see changes was after 5 days of dehydration. 4 Given the metabolic rate and water turnover in mice (daily intake of 4 to 6 mL per 30 g animal), water deprivation for 48 hours is a severe challenge, probably a greater stimulus than in rats. The reason for the species differences in the localization of the response, PVN and AP, is not known.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Neuroendocrine Effects of Dehydration in Mice Lacking the Angiotensin AT1a Receptor

Morris

Callahan

et al. 1999

Hypertension

View full text Add to dashboard Cite

Abstract-Angiotensin (Ang) type 1a (AT1a) receptors are critical in the control of blood pressure and water balance.Experiments were performed to determine the influence of dehydration on brain Ang receptors and plasma vasopressin (VP) in mice lacking this receptor. Control or AT1a knockout (AT1aKO) male mice were give water ad libitum or deprived of water for 48 hours. Animals were anesthetized with halothane, blood samples were collected by heart puncture, and brains were processed for Ang-receptor autoradiography with 125 I-sarthran (0.4 nmol/L). Dehydration produced an increase in AT1 receptors in the paraventricular nucleus (PVN) and anterior pituitary (AP) in control mice (PVN: 70Ϯ16 versus 146Ϯ10 fmol/mg protein; AP: 41Ϯ7 versus 86Ϯ15 fmol/mg protein). No changes were noted in the median preoptic nucleus. The majority of the brain receptors were of the AT1 subtype. There was little or no specific Ang binding in AT1aKO mice and no effect of dehydration. Plasma VP levels were elevated in the halothane-anesthetized animals (Ͼ200 pg/mL) with no significant effect of dehydration. A separate experiment was performed with decapitated mice anesthetized with pentobarbital. Dehydration increased plasma VP in control mice, from 3.3Ϯ0.6 to 13.3Ϯ4.7 pg/mL, whereas no change was noted in the AT1aKO mice, 5.1Ϯ0.3 versus 6.1Ϯ0.7 pg/mL (water versus dehydration). These results demonstrate a differential response to dehydration in mice lacking AT1a receptors. There was no evidence for AT1 receptors of any subtype in the brain regions examined and no effect of dehydration on VP secretion or brain Ang receptors. Key Words: central nervous system Ⅲ hypothalamus Ⅲ vasopressin Ⅲ water balance Ⅲ blood pressure T here are strong links between the renin angiotensin system (RAS) and fluid/electrolyte balance. 1-3 Alterations in volume status produced by dehydration, salt loading, or deprivation result in changes in brain and peripheral angiotensin (Ang) receptors. 4 -8 Dehydration in rats produced an increase in Ang type 1 (AT1) receptors in anterior pituitary (AP) and subfornical organ (SFO), with no change noted in the paraventricular nucleus (PVN). 4,5,9 Salt loading caused an increase in SFO and PVN Ang receptors. 8,10 Physiological interactions are also observed, such as Ang-mediated drinking and vasopressin responses, sodium-induced potentiation of the pressor action of Ang, and angiotensinergic modulation of the response to dehydration. [11][12][13][14] The question that has arisen is the role of the specific AT1 subtypes in the responses. Autoradiographic techniques used to measure receptor density do not distinguish between AT1a and AT1b subtypes because of the structural similarity of the receptors. [15][16][17][18] Likewise, specific pharmacological antagonists are not available. Gene deletion or knockout (KO) methods provide a new way of separating the receptor subtypes in an in vivo model. A comparison of the AT1a and AT1b receptor KO strains supports the idea that AT1a receptors are critical in blood pressure and flu...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Receptor Autoradiographymentioning

confidence: 99%

mentioning

confidence: 95%

mentioning

confidence: 99%

See 2 more Smart Citations

Neuroendocrine Effects of Dehydration in Mice Lacking the Angiotensin AT1a Receptor

Morris

Callahan

et al. 1999

Hypertension

View full text Add to dashboard Cite

show abstract

“…Water deprivation leads to an up-regulation of ANG II receptor binding and AT 1A receptor gene expression (5,53) as well as an increase in steady state AoGen mRNA levels in the rat SFO (5). The simultaneous increase in TTF-1 mRNA and protein and AoGen mRNA observed in the SFO after 2 days of water deprivation suggests that dehydration up-regulates AoGen synthesis in the SFO via activation of TTF-1 production.…”

Section: Ttf-1 Regulates Ang Transcription In Subfornical Organmentioning

confidence: 99%

TTF-1, a Homeodomain-containing Transcription Factor, Participates in the Control of Body Fluid Homeostasis by Regulating Angiotensinogen Gene Transcription in the Rat Subfornical Organ

Son

Hur

Ryu

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

In recent years, it has become increasingly evident that angiotensins synthesized in the brain contribute to regulating body fluid homeostasis. Although angiotensinogen, the unique angiotensin precursor, is produced in the brain, the factors that regulate its gene expression remain unknown. We recently found that TTF-1, a homeodomain-containing transcription factor essential for the development of the fetal diencephalon, is postnatally expressed in discrete areas of the hypothalamus. We now report that the subfornical organ, an important site of angiotensinogen synthesis, is an extrahypothalamic site of TTF-1 expression. Double in situ hybridization histochemistry demonstrated the presence of TTF-1 mRNA in angiotensinogen-producing cells of the rat subfornical organ. RNase protection assays showed that TTF-1 and angiotensinogen mRNA levels are simultaneously increased in the subfornical organ by water deprivation. The angiotensinogen promoter contains seven presumptive TTF-1 binding motifs, four of which are recognized by the TTF-1 homeodomain. In the C6 glioma cell line, TTF-1 transactivates the angiotensinogen promoter in a dose-dependent manner. This transactivation is abolished by deletion of the TTF-1 binding motif at ؊125. Intracranial administration of an antisense TTF-1 oligodeoxynucleotide decreased angiotensinogen mRNA in the subfornical organ and dramatically reduced the animal's water intake while increasing urine excretion. Moreover, plasma arginine vasopressin content was decreased by the same treatment. These results demonstrate a novel role for TTF-1 in the regulation of body fluid homeostasis, exerted via the transactivational control of angiotensinogen synthesis in the subfornical organ.The control of body fluid volume and blood pressure is a critical homeostatic process required for normalcy of the internal environment and for the preservation of life. Many studies have demonstrated that the renin-angiotensin system (RAS) 1 plays an important role in the regulation of fluid volume balance, blood pressure, and other related biological responses through the generation of angiotensin II (ANG II) (1). The existence of a brain RAS in addition to the peripheral RAS has also been established (2, 3). All components of the peripheral RAS have been found in the brain, most notably in the subfornical organ (SFO). The SFO is a circumventricular organ (CVO) of the lamina terminalis located at the top of the dorsal third ventricle (4). It is composed of fenestrated capillary loops in addition to glial cells, but in contrast to other CVOs such as the median eminence of the hypothalamus, it also contains neuronal cell bodies (1, 5). The SFO of rats contains high concentrations of angiotensinogen (AoGen) (6), the angiotensin precursor; renin-like activity (that converts AoGen to ANG I) (7); angiotensin-converting enzyme (which converts ANG I to ANG II) (8); the peptide ANG II (9); and AT 1 -type ANG II receptors (3). Thus, the SFO is not only a target for circulating ANG II, which exerts a potent dipsogenic ef...

show abstract

Ontogeny of angiotensin II type 1 receptor mRNAs in fetal and neonatal rat brain

Nuyt

Lenkei

Corvol

et al. 2001

J of Comparative Neurology

View full text Add to dashboard Cite

Studies have demonstrated a specific function of the angiotensin II (Ang II) type 1 receptor (AT(1)) in regulation of adult central cardiovascular, fluid, and pituitary hormone release and a predominant role of the renin-angiotensin system in fetal and neonatal cardiovascular homeostasis. The pattern of brain AT(1) mRNA expression during fetal and neonatal development is currently unknown. We used radiolabeled cRNA probes for in situ hybridization histochemistry to determine the ontogenic development of the two AT(1) subtypes (AT(1a) and AT(1b)) mRNA in rat brain, from 11 days of gestation (E11) to 28 days after birth (P28). No AT(1b) mRNA was detected in the developing brain, whereas AT(1a) mRNA was first detected at E19. The age at which AT(1a) mRNA is first detected varied among different brain areas and expression predominates in areas involved in fluid homeostasis, pituitary hormone release, and cardiovascular regulation, where it persists until P28. AT(1a) mRNA expression is present from E19 onward in the median preoptic nucleus, the vascular organ of the lamina terminalis, the paraventricular nucleus, the periaqueductal gray, the nucleus raphe pallidus, the motor facial nucleus, and very weakly in the nucleus of the solitary tract and the ambiguous nucleus, and at E21 in the subfornical organ, the anterior olfactory nucleus and the piriform cortex. AT(1a) mRNA expression is present after birth in many regions, including the preoptic and lateral hypothalamic areas, the area postrema and medullary reticular nuclei. In conclusion, during brain development, expression of AT(1a) mRNA, appears in late gestation at E19, predominantly in forebrain areas involved in fluid homeostasis and cardiovascular regulation. In contrast, AT(1a) mRNA expression is absent or present only in very small amounts until after birth in many medullary nuclei, known to play an important role in cardiovascular modulation. Our results suggest that, in perinatal life, AT(1a) is involved in fluid and perhaps cardiovascular homeostasis and that the role of Ang II in modulating medullary cardiovascular centers matures later in postnatal life.

show abstract

Water deprivation upregulates ANG II AT1 binding and mRNA in rat subfornical organ and anterior pituitary

Cited by 34 publications

References 25 publications

Neuroendocrine Effects of Dehydration in Mice Lacking the Angiotensin AT1a Receptor

Neuroendocrine Effects of Dehydration in Mice Lacking the Angiotensin AT1a Receptor

TTF-1, a Homeodomain-containing Transcription Factor, Participates in the Control of Body Fluid Homeostasis by Regulating Angiotensinogen Gene Transcription in the Rat Subfornical Organ

Ontogeny of angiotensin II type 1 receptor mRNAs in fetal and neonatal rat brain

Contact Info

Product

Resources

About