Age and sex influence the response in lipid metabolism of dehydrated Wistar rats.

Aging is associated a decrease in thirst sensation, which makes old people more susceptible to dehydration. Dehydration produces energy metabolism alterations. Our objective was to determinate the effect of water deprivation (WD) in the lipid metabolism of old male and female rats. Here we show that in the state of WD, aging and sex alters retroperitoneal white adipose tissue (R-WAT) weight of rats, WD old female rats had more lipolysis products than old male rats, a sexual dimorphism in the hormonal response related with metabolism of the adipose tissue of old rats during WD, the expression of P-para mRNA in R-WAT did not present any alteration in animals submitted to WD, the expression of Aqp7 mRNA in R-WAT is altered by WD, age, and sex. Also, WD stimulated an increase in the plasma concentration of oxytocin and the expression of mRNA of the oxytocin receptors in R-WAT.

17ß-Estradiol attenuates p38MAPK activity but not PKCα induced by angiotensin II in the brain.

17ß-Estradiol (E2) has been shown to modulate the renin-angiotensin system in hydromineral and blood pressure homeostasis mainly by attenuating angiotensin II (ANGII) actions. However, the cellular mechanisms of the interaction between E2 and angiotensin II (ANGII) and its physiological role are largely unknown. The present experiments were performed to better understand the interaction between ANGII and E2 in body fluid control in female ovariectomized (OVX) rats. The present results are the first to demonstrate that PKC/p38 MAPK signaling is involved in ANGII-induced water and sodium intake and oxytocin (OT) secretion in OVX rats. In addition, previous data from our group revealed that the ANGII-induced vasopressin (AVP) secretion requires ERK1/2 signaling. Therefore, taken together, the present observations support a novel concept that distinct intracellular ANGII signaling gives rise to distinct neurohypophyseal hormone release. Furthermore, the results show that E2 attenuates p38 MAPK phosphorylation in response to ANGII but not PKC activity in the hypothalamus and the lamina terminalis, suggesting that E2 modulates ANGII effects through the attenuation of the MAPK pathway. In conclusion, this work contributes to the further understanding of the interaction between E2 and ANGII signaling in hydromineral homeostasis, as well as it contributes to further elucidate the physiological relevance of PKC/p38 MAPK signaling on the fluid intake and neurohypophyseal release induced by ANGII.

Estradiol and angiotensin II crosstalk in hydromineral balance: Role of the ERK1/2 and JNK signaling pathways.

The angiotensin II (ANGII) receptor AT1 plays an important role in the control of hydromineral balance, mediating the dipsogenic and natriorexigenic effects and neuroendocrine responses of ANGII. While estradiol (E2) is known to modulate several actions of ANGII in the brain, the molecular and cellular mechanisms of the interaction between E2 and ANGII and its physiological role in the control of body fluids remain unclear. We investigated the influence of E2 (40 µg/kg) pretreatment and extracellular-signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) cell signaling on the dipsogenic and natriorexigenic effects, as well as the neuroendocrine responses to angiotensinergic central stimulation in ovariectomized rats (OVX). We showed that the inhibitory effect of E2 on ANGII-induced water and sodium intake requires the ERK1/2 and JNK signaling pathways. On the other hand, E2 pretreatment prevents the ANGII-induced phosphorylation of ERK and JNK in the lamina terminalis. E2 therapy decreased oxytocin (OT) and vasopressin (AVP) secretion and decreased ERK1/2 phosphorylation in the supraoptic and paraventricular nuclei (SON and PVN, respectively). We found that the AVP secretion induced by ANGII required ERK1/2 signaling, but OT secretion did not involve ERK1/2 signaling. Taken together, these results demonstrate that E2 modulates ANGII-induced water and sodium intake and AVP secretion by affecting the ERK1/2 and JNK pathways in the lamina terminalis and ERK1/2 signaling in the hypothalamic nuclei (PVN and SON) in OVX rats.

Effects of hydrogen sulfide (H2S) on water intake and vasopressin and oxytocin secretion induced by fluid deprivation.

During dehydration, responses of endocrine and autonomic control systems are triggered by central and peripheral osmoreceptors and peripheral baroreceptors to stimulate thirst and sodium appetite. Specifically, it is already clear that endocrine system acts by secreting vasopressin (AVP), oxytocin (OT) and angiotensin II (ANG II), and that gaseous molecules, such as nitric oxide (NO) and carbon monoxide (CO), play an important role in modulating the neurohypophyseal secretion as well as ANG II production and thirst. More recently, another gas-hydrogen sulfide (H2S)-has been studied as a neuronal modulator, which is involved in hypothalamic control of blood pressure, heart frequency and temperature. In this study, we aimed to investigate whether H2S and its interaction with NO system could participate in the modulatory responses of thirst and hormonal secretion induced by fluid deprivation. For this purpose, Wistar male rats were deprived of water for 12 and 24h, and the activity of sulfide-generating enzymes was measured. Surprisingly, 24-h water deprivation increased the activity of sulfide-generating enzymes in the medial basal hypothalamus (MBH). Furthermore, the icv injection of sodium sulfide (Na2S, 260nmol), a H2S donor, reduced water intake, increased AVP, OT and CORT plasma concentrations and decreased MBH nitrate/nitrite (NOX) content of 24-h water-deprived animals compared to controls. We thus suggest that H2S system has an important role in the modulation of hormonal and behavioral responses induced by 24-h fluid deprivation.

The role of estradiol in adrenal insufficiency and its interaction with corticosterone on hydromineral balance.

Estradiol (E2) plays an important role in controlling the homeostasis of body fluids. Several studies have reported the involvement of the hypothalamic pituitary adrenal axis (HPA) in the homeostatic control of hydromineral balance and the influence of estrogens on the modulation of this system. Nevertheless, until now, the physiological relevance of HPA axis activity on the hydromineral balance in females has not yet been fully elucidated. Therefore, the objective of the present study was to evaluate the effects of E2 (20 µg/animal) pretreatment on neuroendocrine and hydroelectrolyte changes induced by adrenalectomy (ADX) with or without glucocorticoid hormone replacement (corticosterone, CORT; 10 mg/kg) in ovariectomized rats (OVX). The results show that sodium appetite, natriuresis and the elevated plasma angiotensin II (ANG II) concentration induced by ADX were attenuated by E2 pretreatment. Additionally, a reduction of AT1 mRNA expression in the subfornical organ (SFO) and an increase in plasma atrial natriuretic peptide (ANP) concentrations by E2 pretreatment were observed. E2 pretreatment reversed the reduction in water intake induced by ADX in ADX CORT-replaced rats. Moreover, E2 pretreatment attenuated corticotropin releasing factor (CRF) mRNA expression in the paraventricular nucleus (PVN) induced by ADX. In contrast, E2 pretreatment increased CRF mRNA expression in the PVN in ADX CORT-replaced rats. Taken together, these results suggest that E2 has an important role in the modulation of behavioral and neuroendocrine responses involved in the maintenance of body fluid homeostasis in ADX rats with or without glucocorticoid replacement therapy.

Behavioural changes induced by angiotensin-converting enzyme inhibition during pregnancy and lactation in adult offspring rats.

1. The use of angiotensin-converting enzyme (ACE) inhibitors during pregnancy is contraindicated because of their association with increased risks of fetopathy, including central nervous systems malformations. In addition, some reports have shown that renin-angiotensin system components are expressed differently during embryonic development and adulthood in the rat. 2. Because angiotensin II and its derivative peptides have been implicated in anxiety and modulation of nociception, the aim of the present study was to investigate whether inhibiting ACE during prenatal and neonatal periods would alter behavioural plasticity in adult male offspring rats. 3. Female Wistar rats were treated with captopril (2 mg/mL water; approximately 200 mg/kg per day) during pregnancy and lactation. At adulthood, the offspring were subjected to the open field, elevated plus maze, social interaction, forced swimming and tail flick tests. 4. Perinatal captopril treatment significantly increased ambulation (33%; P < 0.05) and decreased resting time (37.5%; P < 0.05) in the open field test. Perinatal captopril treatment did not alter any of the behavioural parameters of the elevated plus maze; however, captopril treatment did cause a significant increase in social interaction (75.3%; P < 0.05). In the forced swimming test, there was an increased latency period (102.9%; P < 0.001) and a decreased immobility period (38.7, P < 0.05) in rats treated with perinatal captopril. In the tail flick test, perinatal captopril treatment significantly reduced the latency time (26.3%; P < 0.01). 5. The data show that ACE inhibition during prenatal and neonatal periods affects behavioural responses in adult offspring rats, suggesting that ACE is required for the development of neural systems that are associated with adult anxiety and nociceptive behavioural responses.