scholarly journals Activation of Orexin 1 Receptors in the Paraventricular Nucleus Contributes to the Development of Deoxycorticosterone Acetate-Salt Hypertension Through Regulation of Vasopressin

2021 ◽  
Vol 12 ◽  
Author(s):  
Jeremy A. Bigalke ◽  
Huanjia Gao ◽  
Qing-Hui Chen ◽  
Zhiying Shan
Keyword(s):  
Paraventricular Nucleus ◽  
Male Rats ◽  
Deoxycorticosterone Acetate ◽  
Hypertensive Animal ◽  
Salt Hypertension ◽  
Group A ◽  
Hypertension Development ◽  
Salt Sensitive Hypertension ◽  
The Impact ◽  
The Brain

Salt-sensitivity is a major factor in the development of hypertension. The brain orexin system has been observed to play a role in numerous hypertensive animal models. However, orexin’s role in the pathology of salt-sensitive hypertension (SSH) remains to be adequately explored. We assessed the impact of orexin hyperactivity in the pathogenesis of the deoxycorticosterone acetate (DOCA) – salt rat model, specifically through modulation of Arginine Vasopressin (AVP). Adult male rats were separated into three groups: vehicle control, DOCA-salt, and DOCA-salt+OX1R-shRNA. DOCA-salt rats received subcutaneous implantation of a 21-day release, 75 mg DOCA pellet in addition to saline drinking water (1% NaCl and 0.2% KCl). DOCA-salt+OX1R-shRNA rats received bilateral microinjection of AAV2-OX1R-shRNA into the paraventricular nucleus (PVN) to knockdown function of the Orexin 1-Receptor (OX1R) within that area. Following 2-week to allow full transgene expression, a DOCA pellet was administered in addition to saline drinking solution. Vehicle controls received sham DOCA implantation but were given normal water. During the 3-week DOCA-salt or sham treatment period, mean arterial pressure (MAP) and heart rate (HR) were monitored utilizing tail-cuff plethysmography. Following the 3-week period, rat brains were collected for either PCR mRNA analysis, as well as immunostaining. Plasma samples were collected and subjected to ELISA analysis. In line with our hypothesis, OX1R expression was elevated in the PVN of DOCA-salt treated rats when compared to controls. Furthermore, following chronic knockdown of OX1R, the hypertension development normally induced by DOCA-salt treatment was significantly diminished in the DOCA-salt+OX1R-shRNA group. A concurrent reduction in PVN OX1R and AVP mRNA was observed in concert with the reduced blood pressure following AAV2-OX1R-shRNA treatment. Similarly, plasma AVP concentrations appeared to be reduced in the DOCA-salt+OX1R-shRNA group when compared to DOCA-salt rats. These results indicate that orexin signaling, specifically through the OX1R in the PVN are critical for the onset and maintenance of hypertension in the DOCA-salt model. This relationship is mediated, at least in part, through orexin activation of AVP producing neurons, and the subsequent release of AVP into the periphery. Our results outline a promising mechanism underlying the development of SSH through interactions with the brain orexin system.

scholarly journals Effects of edible fats and oils on the body weight gain and on weights of some selected organs in rats removing the impact of unequal feed intake

1970 ◽  
pp. 107-110
Author(s):  
N Ahmad ◽  
S Majumder ◽  
MA Miah ◽  
MJ Uddin
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Feed Intake ◽  
Body Weight Gain ◽  
Fats And Oils ◽  
Male Rats ◽  
Edible Fats ◽  
Group A ◽  
Group B ◽  
The Impact

An investigation on Long Evans male rats fed with different edible fats and oils was conducted in the Department of Physiology, Bangladesh Agricultural University, Mymensingh during a period of 7 weeks (1st April to 19th May, 2005) to determine and to compare the effect of feeds on body weight gain and on weights of some selected organs (heart, liver and kidney) removing the impact of unequal feed intake. A total of 20, six-week old male rats were randomly divided into A, B, C and D groups. Each group consisted of 5 rats. Rats were fed rat pellets purchased from ICDDR,B, Dhaka supplemented with beef fat in group A, fish fat in group B and soybean oil in group C while group D was considered as control and fed only with rat pellets. The concentration of fats and oils were 7% of normal diet and fed for 7 weeks. The highest weekly mean body weight gain (19.90g) adjusted for unequal feed intake was achieved by the rats of beef fat supplemented group A, followed by the rats of soybean oil supplemented group C (19.76g) and fish fat supplemented group B (15.67g). But none of the adjusted means of weekly body weight gain differed significantly (p > 0.05) from the control. Insignificant increases in heart weight were recorded in all treated rats and the maximum weight was in fish oil treated ones. Not much differences were recorded in the kidney weights rather beef oil treated rats' kidney had the lowest mean weight. A significantly (p < 0.01) higher liver weight was recorded in group B & C compared to control (group D), though the differences between A & D were insignificant. It could be concluded that fats and oils are harmful for the rat's body especially on liver and heart. Key words: Edible fats and oils, rat, body weight, organ weight, analysis of variance, covariance DOI = 10.3329/bjvm.v5i1.1326 Bangl. J. Vet. Med. (2007). 5 (1 & 2): 107-110

scholarly journals Exacerbated effects of prorenin on hypothalamic magnocellular neuronal activity and vasopressin plasma levels during salt-sensitive hypertension

2019 ◽  
Vol 317 (3) ◽  
pp. H496-H504
Author(s):  
Soledad Pitra ◽  
Caleb J. Worker ◽  
Yumei Feng ◽  
Javier E. Stern
Keyword(s):  
Plasma Levels ◽  
Renin Angiotensin System ◽  
Membrane Excitability ◽  
Hypertensive Rats ◽  
Deoxycorticosterone Acetate ◽  
Type K ◽  
Neurosecretory Neurons ◽  
Salt Hypertension ◽  
Underlying Mechanisms ◽  
Salt Sensitive Hypertension

Accumulating evidence supports that the brain renin-angiotensin system (RAS), including prorenin (PR) and its receptor (PRR), two newly discovered RAS players, contribute to sympathoexcitation in salt-sensitive hypertension. Still, whether PR also contributed to elevated circulating levels of neurohormones such as vasopressin (VP) during salt-sensitive hypertension, and if so, what are the precise underlying mechanisms, remains to be determined. To address these questions, we obtained patch-clamp recordings from hypothalamic magnocellular neurosecretory neurons (MNNs) that synthesize the neurohormones oxytocin and VP in acute hypothalamic slices obtained from sham and deoxycorticosterone acetate (DOCA)-salt-treated hypertensive rats. We found that focal application of PR markedly increased membrane excitability and firing responses in MNNs of DOCA-salt, compared with sham rats. This effect included a shorter latency to spike initiation and increased numbers of spikes in response to depolarizing stimuli and was mediated by a more robust inhibition of A-type K+ channels in DOCA-salt compared with sham rats. On the other hand, the afterhyperpolarizing potential mediated by the activation of Ca2+-dependent K+ channel was not affected by PR. mRNA expression of PRR, VP, and the Kv4.3 K+ channel subunit in the supraoptic nucleus of DOCA-salt hypertensive rats was increased compared with sham rats. Finally, we report a significant decrease of plasma VP levels in neuron-selective PRR knockdown mice treated with DOCA-salt, compared with wild-type DOCA-salt-treated mice. Together, these results support that activation of PRR contributes to increased excitability and firing discharge of MNNs and increased plasma levels of VP in DOCA-salt hypertension. NEW & NOTEWORTHY Our studies support that prorenin (PR) and its receptor (PRR) within the hypothalamus contribute to elevated plasma vasopressin levels in deoxycorticosterone acetate-salt hypertension, in part because of an exacerbated effect of PR on magnocellular neurosecretory neuron excitability; Moreover, our study implicates A-type K+ channels as key underlying molecular targets mediating these effects. Thus, PR/PRR stands as a novel therapeutic target for the treatment of neurohumoral activation in salt-sensitive hypertension.

scholarly journals LGR4 and Its Ligands, R-Spondin 1 and R-Spondin 3, Regulate Food Intake in the Hypothalamus of Male Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 429-440 ◽  
Author(s):  
Ji-Yao Li ◽  
Biaoxin Chai ◽  
Weizhen Zhang ◽  
Danielle M. Fritze ◽  
Chao Zhang ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Paraventricular Nucleus ◽  
Median Eminence ◽  
Energy Homeostasis ◽  
Male Rats ◽  
The Third ◽  
The Brain

The hypothalamus plays a key role in the regulation of feeding behavior. Several hypothalamic nuclei, including the arcuate nucleus (ARC), paraventricular nucleus, and ventromedial nucleus of the hypothalamus (VMH), are involved in energy homeostasis. Analysis of microarray data derived from ARC revealed that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is highly expressed. LGR4, LGR5, and LGR6 form a subfamily of closely related receptors. Recently, R-spondin (Rspo) family proteins were identified as ligands of the LGR4 subfamily. In the present study, we investigated the distribution and function of LGR4–LGR6 and Rspos (1–4) in the brain of male rat. In situ hybridization showed that LGR4 is expressed in the ARC, VMH, and median eminence of the hypothalamus. LGR4 colocalizes with neuropeptide Y, proopiomelanocortin, and brain-derived neurotrophic factor neurons. LGR5 is not detectable with in situ hybridization; LGR6 is only expressed in the epithelial lining of the lower portion of the third ventricle and median eminence. Rspo1 is expressed in the VMH and down-regulated with fasting. Rspo3 is expressed in the paraventricular nucleus and also down-regulated with fasting. Rspos 1 and 3 colocalize with the neuronal marker HuD, indicating that they are expressed by neurons. Injection of Rspo1 or Rspo3 into the third brain ventricle inhibited food intake. Rspo1 decreased neuropeptide Y and increased proopiomelanocortin expression in the ARC. Rspo1 and Rspo3 mRNA is up-regulated by insulin. These data indicate that Rspo1 and Rspo3 and their receptor LGR4 form novel circuits in the brain to regulate energy homeostasis.

scholarly journals Importance of the Paraventricular Nucleus of the Hypothalamus as a Component of a Neural Pathway between the Brain and the Testes that Modulates Testosterone Secretion Independently of the Pituitary

Endocrinology ◽  
2003 ◽  
Vol 144 (2) ◽  
pp. 594-598 ◽  
Author(s):  
Daniel J. Selvage ◽  
Catherine Rivier
Keyword(s):  
Paraventricular Nucleus ◽  
Leydig Cell ◽  
Pseudorabies Virus ◽  
Cell Function ◽  
Brain Area ◽  
Male Rats ◽  
Neural Pathway ◽  
Electrolytic Lesions ◽  
The Brain

We previously reported that in adult male rats, the intracerebroventricular (icv) injection of corticotropin-releasing factor (CRF) or the β-adrenergic agonist isoproterenol (ISO) significantly inhibited the ability of human chorionic gonadotropin (hCG) to stimulate testosterone (T) secretion. The finding that this phenomenon also took place when LH release had been blocked with an LHRH antagonist suggested that icv CRF and ISO did not alter Leydig cell function by influencing the activity of pituitary gonadotrophs. We therefore proposed the existence of a neural pathway connecting the brain to the testes, whose activation by icv CRF or ISO interfered with T secretion. Based on the intratesticular injection of the transganglionic tracer pseudorabies virus, we recently identified the paraventricular nucleus (PVN) of the hypothalamus as a component of this neural link. The aim of the present work was to investigate the functional role of this brain area in mediating the ability of CRF and ISO to inhibit the ability of hCG to stimulate T secretion. We first demonstrated that local microinfusion of CRF or ISO directly into the PVN mimicked the effect of their icv injection, suggesting that the PVN does indeed represent a site of action of ISO and CRF in altering Leydig cell responsiveness to gonadotropin. In contrast, neither CRF nor ISO microinfusion into the central amygdala or the frontal cortex influenced hCG-stimulated T secretion. To further investigate the role of the PVN in ISO- and CRF-induced blunting of hCG stimulation of T, we determined the effect of icv CRF or ISO on testicular activity of rats with electrolytic lesions of the PVN. These lesions, which did not in themselves influence Leydig cell responsiveness to hCG, blocked the effect of both icv ISO and CRF on hCG-induced T release. Collectively, these results support the hypothesis that CRF- and ISO-induced activation of cells in the area of the PVN decreases the ability of gonadotropin to release T and suggests that this nucleus represents an important site of the proposed neural connection between the brain and the testes.

scholarly journals β-Arrestin–Biased Agonist Targeting the Brain AT 1 R (Angiotensin II Type 1 Receptor) Increases Aversion to Saline and Lowers Blood Pressure in Deoxycorticosterone Acetate–Salt Hypertension

Hypertension ◽  
2020 ◽  
Author(s):  
Mario Zanaty ◽  
Fernando A.C. Seara ◽  
Pablo Nakagawa ◽  
Guorui Deng ◽  
Natalia M. Mathieu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Central Administration ◽  
Deoxycorticosterone Acetate ◽  
Intracerebroventricular Infusion ◽  
Salt Hypertension ◽  
Saline Solutions ◽  
The Brain ◽  
Biased Agonist

Activation of central AT 1 Rs (angiotensin type 1 receptors) is required for the increased blood pressure, polydipsia, and salt intake in deoxycorticosterone acetate (DOCA)–salt hypertension. TRV120027 (TRV027) is an AT 1 R-biased agonist that selectively acts through β-arrestin. We hypothesized that intracerebroventricular administration of TRV027 would ameliorate the effects of DOCA-salt. In a neuronal cell line, TRV027 induced AT 1a R internalization through dynamin and clathrin-mediated endocytosis. We next evaluated the effect of chronic intracerebroventricular infusion of TRV027 on fluid intake. We measured the relative intake of water versus various saline solutions using a 2-bottle choice paradigm in mice subjected to DOCA with a concomitant intracerebroventricular infusion of either vehicle, TRV027, or losartan. Sham mice received intracerebroventricular vehicle without DOCA. TRV027 potentiated DOCA-induced water intake in the presence or absence of saline. TRV027 and losartan both increased the aversion for saline—an effect particularly pronounced for highly aversive saline solutions. Intracerebroventricular Ang (angiotensin) II, but not TRV027, increased water and saline intake in the absence of DOCA. In a separate cohort, blood pressure responses to acute intracerebroventricular injection of vehicle, TRV, or losartan were measured by radiotelemetry in mice with established DOCA-salt hypertension. Central administration of intracerebroventricular TRV027 or losartan each caused a significant and similar reduction of blood pressure and heart rate. We conclude that administration of TRV027 a selective β-arrestin biased agonist directly into the brain increases aversion to saline and lowers blood pressure in a model of salt-sensitive hypertension. These data suggest that selective activation of AT 1 R β-arrestin pathways may be exploitable therapeutically.

scholarly journals EXPERIMENTAL STUDY OF THE IMPACT OF LOW FLUORINE CONCENTRATIONS ON THE TISSUE LEVEL OF HSP FAMILY PROTEINS

2018 ◽  
Vol 97 (7) ◽  
pp. 604-608
Author(s):  
Anna G. Zhukova ◽  
L. G. Gorokhova ◽  
A. V. Kiseleva ◽  
T. G. Sazontova ◽  
N. N. Mikhailova
Keyword(s):  
Toxic Effect ◽  
White Male ◽  
Antioxidant Properties ◽  
Tissue Level ◽  
Male Rats ◽  
Laboratory Animals ◽  
Heme Oxygenase 1 ◽  
Sensitive Organ ◽  
The Impact ◽  
The Brain

Introduction. Fluoride in high concentrations has a toxic effect not only on bone tissue but also on the heart, liver, kidneys, and brain. In the implementation of the response to toxic doses of fluorine the proteins of the HSP family are involved regulating intracellular and tissue homeostasis under various stress effects. The toxic effect of high fluorine concentrations the mechanisms of which are disclosed in fluorosis can be realized and at a level significantly lower than a toxic one. In the literature, there is little data on the peculiarities of the effects of low fluorine concentrations at the tissue and cellular levels. The aim of the study. To investigate the impact of low fluorine concentrations on the tissue level of HSP family proteins in the brain and liver of laboratory animals. Material and methods. The experiments were carried out on 60 white male rats of the same age weighing 200-250 g. The rats were divided into 2 groups: the control and the group of the animals exposed to sodium fluoride (NaF) within 6 weeks (at a concentration of 10 mg/l corresponding to the daily fluorine dose of 1.2 mg/kg per body weight). We determined the level of inducible HSP72 and HSP32 (heme-oxygenase-1) referred to proteins of HSP family (Heat shock proteins), the activity of free radical processes and antioxidant enzymes (superoxide dismutase (SOD) and catalase) in the brain and liver tissues. Results. The important role of stress-inducible HSP72 protein in protecting the brain from the damage caused by the prolonged exposure to low fluorine concentrations was shown. In the liver, a protective role against fluoride exposure is played by the protein HSP32 with antioxidant properties. At the tissue level, the prolongation of the terms of the development of chronic fluoride intoxication with low fluorine concentrations was revealed. In the liver appeared to be the highly sensitive organ to the fluorine accumulation, the significant lesion was detected.

scholarly journals Brain ACE2 overexpression reduces DOCA-salt hypertension independently of endoplasmic reticulum stress

2015 ◽  
Vol 308 (5) ◽  
pp. R370-R378 ◽  
Author(s):  
Huijing Xia ◽  
Thyago Moreira de Queiroz ◽  
Srinivas Sriramula ◽  
Yumei Feng ◽  
Tanya Johnson ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Fluorescent Protein ◽  
Brain Regions ◽  
Salt Treatment ◽  
Neurogenic Hypertension ◽  
Beneficial Effects ◽  
Salt Hypertension ◽  
The Impact ◽  
The Brain

Endoplasmic reticulum (ER) stress was previously reported to contribute to neurogenic hypertension while neuronal angiotensin-converting enzyme type 2 (ACE2) overexpression blunts the disease. To assess which brain regions are important for ACE2 beneficial effects and the contribution of ER stress to neurogenic hypertension, we first used transgenic mice harboring a floxed neuronal hACE2 transgene (SL) and tested the impact of hACE2 knockdown in the subfornical organ (SFO) and paraventricular nucleus (PVN) on deoxycorticosterone acetate (DOCA)-salt hypertension. SL and nontransgenic (NT) mice underwent DOCA-salt or sham treatment while infected with an adenoassociated virus (AAV) encoding Cre recombinase (AAV-Cre) or a control virus (AAV-green fluorescent protein) to the SFO or PVN. DOCA-salt-induced hypertension was reduced in SL mice, with hACE2 overexpression in the brain. This reduction was only partially blunted by knockdown of hACE2 in the SFO or PVN, suggesting that both regions are involved but not essential for ACE2 regulation of blood pressure (BP). DOCA-salt treatment did not increase the protein levels of ER stress and autophagy markers in NT mice, despite a significant increase in BP. In addition, these markers were not affected by hACE2 overexpression in the brain, despite a significant reduction of hypertension in SL mice. To further assess the role of ER stress in neurogenic hypertension, NT mice were infused intracerebroventricularlly with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, during DOCA-salt treatment. However, TUDCA infusion failed to blunt the development of hypertension in NT mice. Our data suggest that brain ER stress does not contribute to DOCA-salt hypertension and that ACE2 blunts neurogenic hypertension independently of ER stress.

scholarly journals Vasopressin Administration into the Paraventricular Nucleus Normalizes Plasma Oxytocin and Corticosterone Levels in Brattleboro Rats

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2791-2798 ◽  
Author(s):  
Dóra Zelena ◽  
Kristina Langnaese ◽  
Ágnes Domokos ◽  
Ottó Pintér ◽  
Rainer Landgraf ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Stress Responses ◽  
Extracellular Fluid ◽  
Plasma Corticosterone ◽  
Forced Swimming ◽  
Male Rats ◽  
Congenital Absence ◽  
Mrna Levels ◽  
Intact Control ◽  
The Impact

Adult male rats of the Brattleboro strain were used to investigate the impact of the congenital absence of vasopressin on plasma adrenocorticotropin, corticosterone, and oxytocin concentrations as well as the release pattern of oxytocin within the hypothalamic paraventricular nucleus (PVN), in response to a 10-min forced swimming session. Measurement of adrenocorticotropin in plasma samples collected via chronically implanted jugular venous catheters revealed virtually identical stress responses for vasopressin-lacking Brattleboro (KO) and intact control animals. In contrast, plasma corticosterone and oxytocin levels were found to be significantly elevated 105 min after onset of the stressor in KO animals only. Microdialysis samples collected from the extracellular fluid of the PVN showed significantly higher levels of oxytocin both under basal conditions and in response to stressor exposure in KO vs. intact control animals accompanied by elevated oxytocin mRNA levels in the PVN of KO rats. These findings suggest that the increased oxytocin levels in the PVN caused by the congenital absence of vasopressin may contribute to normal adrenocorticotropin stress responses in KO animals. However, whereas the stressor-induced elevation of plasma oxytocin in KO rats may be responsible for their maintained corticosterone levels, oxytocin seems unable to fully compensate for the lack of vasopressin. This hypothesis was tested by retrodialyzing synthetic vasopressin into the PVN area concomitantly with blood sampling in KO animals. Indeed, this treatment normalized plasma oxytocin and corticosterone levels 105 min after forced swimming. Thus, endogenous vasopressin released within the PVN is likely to act as a paracrine signal to facilitate the return of plasma oxytocin and corticosterone to basal levels after acute stressor exposure.

Effect of suckling on gastric motility in lactating rats

1991 ◽  
Vol 261 (1) ◽  
pp. R38-R43 ◽  
Author(s):  
D. L. Helmreich ◽  
E. Thiels ◽  
A. F. Sved ◽  
J. G. Verbalis ◽  
E. M. Stricker
Keyword(s):  
Gastric Emptying ◽  
Paraventricular Nucleus ◽  
Gastric Motility ◽  
Male Rats ◽  
Inhibitory Effects ◽  
Gastric Function ◽  
Systemic Injection ◽  
Pituitary Secretion ◽  
Oxytocinergic Neurons ◽  
The Brain

Recent reports indicate that in male rats dehydration, LiCl, and cholecystokinin (CCK) each stimulate pituitary oxytocin (OT) secretion and also decrease gastric emptying and motility. In contrast, the present experiments demonstrate that nipple attachment and sucking by pups, a well-known stimulus for neurohypophysial secretion of OT, did not decrease gastric motility in lactating rats. Moreover, systemic injection of naloxone, which is known to potentiate the inhibitory effects of LiCl and CCK on gastric motility in male rats, had no effect on gastric motility of lactating rats while nursing. These data indicate that pituitary OT secretion from magnocellular neurons is not invariably linked to decreased gastric motility in rats. As such, our results support previous findings that inhibition of gastric motility is not secondary to the pituitary secretion of OT but allow a possible role for parvocellular oxytocinergic neurons that project from the hypothalamic paraventricular nucleus to the brain stem in the control of gastric function.

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