RESUMEN
The aim of the present study was to determine whether the TRPV1 channel is involved in the onset of sodium appetite. For this purpose, we used TRPV1-knockout mice to investigate sodium depletion-induced drinking at different times (2/24 h) after furosemide administration combined with a low sodium diet (FURO-LSD). In sodium depleted wild type and TRPV1 KO (SD-WT/SD-TPRV1-KO) mice, we also evaluated the participation of other sodium sensors, such as TPRV4, NaX and angiotensin AT1-receptors (by RT-PCR), as well as investigating the pattern of neural activation shown by Fos immunoreactivity, in different nuclei involved in hydromineral regulation. TPRV1 SD-KO mice revealed an increased sodium preference, ingesting a higher hypertonic cocktail in comparison with SD-WT mice. Our results also showed in SD-WT animals that SFO-Trpv4 expression increased 2 h after FURO-LSD, compared to other groups, thus supporting a role of SFO-Trpv4 channels during the hyponatremic state. However, the SD-TPRV1-KO animals did not show this early increase, and maybe as a consequence drank more hypertonic cocktail. Regarding the SFO-NaX channel expression, in both genotypes our findings revealed a reduction 24 h after FURO-LSD. In addition, there was an increase in the OVLT-NaX expression of SD-WT 24 h after FURO-LSD, suggesting the participation of OVLT-NaX channels in the appearance of sodium appetite, possibly as an anticipatory response in order to limit sodium intake and to induce thirst. Our work demonstrates changes in the expression of different osmosodium-sensitive channels at specific nuclei, related to the body sodium status in order to stimulate an adequate drinking.
Asunto(s)
Apetito/genética , Encéfalo/metabolismo , Dieta Hiposódica , Sodio en la Dieta/administración & dosificación , Canales Catiónicos TRPV/fisiología , Animales , Apetito/efectos de los fármacos , Dieta Hiposódica/efectos adversos , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Líquidos/genética , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/genética , Furosemida/farmacología , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Sodio en la Dieta/metabolismo , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo , Sed/efectos de los fármacos , Sed/fisiologíaRESUMEN
Clinical and basic findings indicate that angiotensin II (ANG II) differentially modulates hydroelectrolyte and cardiovascular responses in male and female. But are only the activational and organizational hormonal effects to blame for such differences? Males and females not only differ in their sex (males are born with testes and females with ovaries) but also carry different sex chromosome complements and are thus influenced throughout life by different genomes. In this review, we discuss our recent studies in order to evaluate whether sex chromosome complement is in part responsible for gender differences previously observed in ANG II bradycardic-baroreflex response and sodium depletion-induced sodium appetite and neural activity. To test the hypothesis that XX or XY contributes to the dimorphic ANG II bradycardic-baroreflex response, we used the four core genotype mouse model, in which the effects of gonadal sex (testes or ovaries) and sex chromosome complement (XX or XY) are dissociated. The results indicate that ANG II bradycardic-baroreflex sexual dimorphic response may be ascribed to differences in sex chromosomes, indicating an XX-sex chromosome complement facilitatory bradycardic-baroreflex control of heart rate. Furthermore, we evaluated whether genetic differences within the sex chromosome complement may differentially modulate the known sexually dimorphic sodium appetite as well as basal or induced brain activity due to physiological stimulation of the renin-angiotensin system by furosemide and low-sodium treatment. Our studies demonstrate an organizational hormonal effect on sexually dimorphic induced sodium intake in mice, while at the brain level (subfornical organ and area postrema) we showed a sex chromosome complement effect in sodium-depleted mice, suggesting a sex chromosome gene participation in the modulation of neural pathways underlying regulatory response to renin-angiotensin stimulation.
Asunto(s)
Barorreflejo/fisiología , Líquidos Corporales/fisiología , Bradicardia/fisiopatología , Homeostasis/fisiología , Caracteres Sexuales , Sodio en la Dieta , Angiotensina II/farmacología , Animales , Apetito/efectos de los fármacos , Apetito/genética , Apetito/fisiología , Barorreflejo/efectos de los fármacos , Barorreflejo/genética , Líquidos Corporales/efectos de los fármacos , Bradicardia/genética , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/genética , Frecuencia Cardíaca/fisiología , Homeostasis/efectos de los fármacos , Homeostasis/genética , Masculino , Ratones , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/genética , Sistema Renina-Angiotensina/fisiología , Cromosomas SexualesRESUMEN
Exposure to an altered osmotic environment during a pre/postnatal period can differentially program the fluid intake and excretion pattern profile in a way that persists until adulthood. However, knowledge about the programming effects on the underlying brain neurochemical circuits of thirst and hydroelectrolyte balance, and its relation with behavioral outputs, is limited. We evaluated whether early voluntary intake of hypertonic NaCl solution may program adult offspring fluid balance, plasma vasopressin, neural activity, and brain vasopressin and angiotensinergic receptor type 1a (AT1a)-receptor gene expression. The manipulation (M) period covered dams from 1 week before conception until offspring turned 1-month-old. The experimental groups were (i) Free access to hypertonic NaCl solution (0.45 M NaCl), food (0.18% NaCl) and water [M-Na]; and (ii) Free access to food and water only [M-Ctrol]. Male offspring (2-month-old) were subjected to iv infusion (0.15 ml/min) of hypertonic (1.5M NaCl), isotonic (0.15M NaCl) or sham infusion during 20 min. Cumulative water intake (140 min) and drinking latency to the first lick were recorded from the start of the infusion. Our results indicate that, after systemic sodium overload, the M-Na group had increased water intake, and diminished neuronal activity (Fos-immunoreactivity) in the subfornical organ (SFO) and nucleus of the solitary tract. They also showed reduced relative vasopressin (AVP)-mRNA and AT1a-mRNA expression at the supraoptic nucleus and SFO, respectively. The data indicate that the availability of a rich source of sodium during the pre/postnatal period induces a long-term effect on drinking, neural activity, and brain gene expression implicated in the control of hydroelectrolyte balance.
Asunto(s)
Encéfalo/citología , Ingestión de Líquidos/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Neuronas/metabolismo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Solución Salina Hipertónica/efectos adversos , Factores de Edad , Animales , Animales Recién Nacidos , Femenino , Estudios de Seguimiento , Masculino , Embarazo , Ratas , Ratas Wistar , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 1/metabolismo , Factores de Tiempo , Vasopresinas/genética , Vasopresinas/metabolismo , Equilibrio Hidroelectrolítico/efectos de los fármacosRESUMEN
Our aim was to analyze the participation of inhibitory and stimulatory signals in the temporal dissociation between sodium depletion (SD) induced by peritoneal dialysis (PD) and the appearance of sodium appetite (SA), particularly 2h after PD, when the rats are hypovolemic/natremic but SA is not evident. We investigated the effects of bilateral injections of the serotonin (5-HT) receptor antagonist, methysergide, into the lateral parabrachial nucleus (LPBN) on hypertonic NaCl and water intake 2h vs. 24h after PD. We also studied plasma renin activity (PRA) and aldosterone (ALDO) concentration 2h vs. 24h after PD. Additionally, we combined the analysis of brain Fos immunoreactivity (Fos-ir) with the detection of double immunoreactivity in 5HT and oxytocinergic (OT) cells 2h after PD. Bilateral LPBN injections of methysergide (4µg/200nl at each site) increased NaCl intake when tested 2h after PD compared to controls. We found a significant increase in PRA and ALDO concentration after PD but no differences between 2 and 24h after PD. We also found for the first time a significant increase 2h after PD in the number of Fos-ir neurons in the brainstem nuclei that have been shown to be involved in the inhibition of SA. In summary, the results show that 5HT-mechanisms in the LPBN modulate sodium intake during the delay of SA when the renin angiotensin aldosterone system (RAAS) is increased. In addition, the activation of brainstem areas previously associated with the satiety phase of SA is in part responsible for the temporal dissociation between SD and behavioral arousal.
Asunto(s)
Apetito/fisiología , Encéfalo/metabolismo , Conducta de Ingestión de Líquido/fisiología , Sodio/metabolismo , Administración Oral , Aldosterona/sangre , Animales , Apetito/efectos de los fármacos , Conducta de Ingestión de Líquido/efectos de los fármacos , Glucosa/administración & dosificación , Masculino , Metisergida/farmacología , Proteínas Oncogénicas v-fos/metabolismo , Oxitocina/metabolismo , Núcleos Parabraquiales/efectos de los fármacos , Ratas , Ratas Wistar , Renina/sangre , Solución Salina Hipertónica/administración & dosificación , Serotonina/metabolismo , Antagonistas de la Serotonina/farmacología , Factores de Tiempo , Equilibrio HidroelectrolíticoRESUMEN
Osmoregulatory mechanisms can be vulnerable to electrolyte and/or endocrine environmental changes during the perinatal period, differentially programming the developing offspring and affecting them even in adulthood. The aim of this study was to evaluate whether availability of hypertonic sodium solution during the perinatal period may induce a differential programming in adult offspring osmoregulatory mechanisms. With this aim, we studied water and sodium intake after Furosemide-sodium depletion in adult offspring exposed to hypertonic sodium solution from 1 week before mating until postnatal day 28 of the offspring, used as a perinatal manipulation model [PM-Na group]. In these animals, we also identified the cell population groups in brain nuclei activated by Furosemide-sodium depletion treatment, analyzing the spatial patterns of Fos and Fos-vasopressin immunoreactivity. In sodium depleted rats, sodium and water intake were significantly lower in the PM-Na group vs. animals without access to hypertonic sodium solution [PM-Ctrol group]. Interestingly, when comparing the volumes consumed of both solutions in each PM group, our data show the expected significant differences between both solutions ingested in the PM-Ctrol group, which makes an isotonic cocktail; however, in the PM-Na group there were no significant differences in the volumes of both solutions consumed after Furosemide-sodium depletion, and therefore the sodium concentration of total fluid ingested by this group was significantly higher than that in the PM-Ctrol group. With regard to brain Fos immunoreactivity, we observed that Furosemide-sodium depletion in the PM-Na group induced a higher number of activated cells in the subfornical organ, ventral subdivision of the paraventricular nucleus and vasopressinergic neurons of the supraoptic nucleus than in the PM-Ctrol animals. Moreover, along the brainstem, we found a decreased number of sodium depletion-activated cells within the nucleus of the solitary tract of the PM-Na group. Our data indicate that early sodium availability induces a long-term effect on fluid drinking and on the cell activity of brain nuclei involved in the control of hydromineral balance. These results also suggest that availability of a rich source of sodium during the perinatal period may provoke a larger anticipatory response in the offspring, activating the vasopressinergic system and reducing thirst after water and sodium depletion, as a result of central osmosensitive mechanism alterations.
Asunto(s)
Solución Salina Hipertónica/farmacología , Equilibrio Hidroelectrolítico/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Líquidos/fisiología , Femenino , Furosemida/farmacología , Masculino , Imagen Molecular/métodos , Imagen Molecular/estadística & datos numéricos , Embarazo , Ratas , Ratas Wistar , Sodio/deficiencia , Sodio/metabolismo , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
In the present study, we investigated the degree to which ß-endorphin plays a role in the alpha 2-adrenergic/imidazoline receptor agonist attenuation of salt appetite. In order to evaluate whether the inhibitory action of clonidine (an α2-adrenergic/imidazoline receptor agonist) on induced sodium intake is mediated by the ß-endorphinergic system, we used a ß-endorphin deficient mouse line. ß-endorphin knockout (ßend(-/-)), heterozygous (ßend(+/-)) and wild-type (ßend(+/+)) mice were submitted to acute sodium depletion by a combined treatment of furosemide and low sodium diet and, 20h later, were administered with clonidine (0.5mg/kg). An hour later, the animals were subjected to a two-bottle choice test (water/2% NaCl). The results indicate that clonidine administration during the first stage of the test exerts an equivalent inhibition on sodium intake regardless of the genotype; however, in the final stage of the test, a reversal of the inhibitory response on induced sodium appetite becomes evident in the mice lacking ß-endorphin. Moreover no differences in dipsogenic response were observed between the genotypes. Considering these results and the fact that plasma half-life of clonidine at the dose administered is approximately 3h, it is possible to speculate that the inhibitory effect of clonidine on sodium appetite may be independent of ß-endorphin modulation during the first stage; however, the long-lasting inhibitory effect of clonidine may be mediated by the ß-endorphinergic system. This evidence supports the existence of adrenergic and ß-endorphinergic system interaction in the osmoregulatory response to achieve sodium balance.