Abstract P284: Neuron Specific (Pro)renin Receptor Knockout Reduces Sodium Appetite and Attenuates the Development of DOCA-salt Induced Hypertension

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Fatima Trebak ◽  
Wencheng Li ◽  
Yumei Feng
Keyword(s):  
Fluid Intake ◽  
Sodium Intake ◽  
Renin Angiotensin System ◽  
Urinary Sodium Excretion ◽  
Free Access ◽  
Salt Treatment ◽  
Total Fluid Intake ◽  
Sodium Appetite ◽  
Induced Hypertension ◽  
Total Fluid

The (pro) renin receptor (PRR) is a key component of the renin-angiotensin system that is highly expressed in the brain. We previously showed that the neuronal PRR deletion attenuates deoxycorticosterone acetate (DOCA)-salt induced hypertension. However, the mechanism underlying remains unclear. To test our hypothesis that PRR is involved in the regulation of sodium appetite during DOCA-salt hypertension, we used a neuron-specific PRR knockout (PRRKO) mouse model generated using the Cre-LoxP system. The PRRKO and their wildtype controls (WT) were implanted with 50 mg DOCA pellet with free access to regular water and 0.9 % saline as the drinking solution. Blood pressure (BP) was monitored by telemetry system in conscious free moving mice. The fluid intake and urine output were monitored along 21 days of DOCA-Salt treatment. The BP is significantly lower in PRRKO compared with WT mice following 21 days of DOCA-salt treatment (112 ± 2 vs. 134 ± 7 mmHg, P= 0.0186). Interestingly, we found that saline intake (27.8 ± 1.8 vs. 15.9 ± 1.2 ml/day, P=0.0007) and total fluid intake (31.1 ± 1.9 vs. 21.1 ± 1.4 ml/day, P=0.003) were higher; while the regular water intake was lower (3.4 ± 0.6 vs. 5.2 ± 0.3 ml/day, P=0.03) in WT compared to PRRKO mice. PRR deletion in the neurons reduced sodium appetite presented as the ratio of saline intake over total fluid intake (0.75 ± 0.016 vs. 0.89 ± 0.019, P=0.0005), as well as total sodium intake (2.45 ± 0.19 vs. 4.28 ± 0.28 mmol/day, P=0.0007) compared with WT mice at the end of the protocol. In addition, the urinary sodium excretion was lower (13.3±1.17 vs. 20±1.17 mmol/day, P<0.0001), but not potassium excretion (0.64 ± 0.028 vs. 0.56 ± 0.05 mmol/day, P=0.1291) in PRRKO compared with WT mice; however, there is no difference in urine sodium and potassium concentrations. Furthermore, plasma vasopressin level (19.0 ± 2.7 vs. 33.6 ± 2.7 pg/ml, P=0.0037) is lower in the PRRKO compared with WT mice at the end of DOCA-salt treatment. In summary, PRR deletion in the neurons reduced sodium appetite, circulating vasopressin level, and attenuated the development of DOCA-salt induced hypertension. Taken together, the present findings suggest that PRR regulates the BP and plays a key role in salt-sensitive hypertension, at least in part, by modulating sodium appetite.

scholarly journals Neuronal (pro)renin receptor regulates deoxycorticosterone-induced sodium intake

2018 ◽  
Vol 50 (10) ◽  
pp. 904-912 ◽  
Author(s):  
Fatima Trebak ◽  
Wencheng Li ◽  
Yumei Feng
Keyword(s):  
Sodium Intake ◽  
Renin Angiotensin System ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Sodium Balance ◽  
Total Fluid Intake ◽  
Sodium Deficiency ◽  
Sodium Appetite ◽  
The Central Nervous System ◽  
Salt Sensitive Hypertension

Increased sodium appetite is a physiological response to sodium deficiency; however, it has also been implicated in disease conditions such as congestive heart failure, kidney failure, and salt-sensitive hypertension. The central nervous system is the major regulator of sodium appetite and intake behavior; however, the neural mechanisms underlying this behavior remain incompletely understood. Here, we investigated the involvement of the (pro)renin receptor (PRR), a component of the brain renin-angiotensin system, in the regulation of sodium intake in a neuron-specific PRR knockout (PRRKO) mouse model generated previously in our laboratory. Sodium intake following deoxycorticosterone (DOCA) stimulation was tested by assessing the preference of mice for 0.9% saline or regular water in single-animal metabolic cages. Blood pressure was monitored in conscious, freely moving mice by a telemetry system. We found that saline intake and total fluid intake were significantly reduced in PRRKO mice following DOCA treatment compared with that in wild-type (WT) mice, whereas regular water intake was similar between the genotypes. Sodium preference and total sodium intake were significantly reduced in PRRKO mice compared with WT mice. PRRKO mice also excreted less urine and urinary sodium compared with WT mice following DOCA treatment, whereas potassium excretion was similar between the two groups. Finally, we found that the sodium balance, calculated by subtracting urinary sodium excretion from sodium intake, was greater in WT mice than in PRRKO mice. Collectively, these findings suggest that the neuronal PRR plays a regulatory role in DOCA-induced sodium intake.

scholarly journals Total fluid intake of children and adolescents: cross-sectional surveys in 13 countries worldwide

2015 ◽  
Vol 54 (S2) ◽  
pp. 57-67 ◽  
Author(s):  
Iris Iglesia ◽  
Isabelle Guelinckx ◽  
Pilar M. De Miguel-Etayo ◽  
Esther M. González-Gil ◽  
Jordi Salas-Salvadó ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Fluid Intake ◽  
Total Fluid Intake ◽  
Cross Sectional ◽  
Total Fluid

scholarly journals Drinking Water Upon Awakening, a Habit Related To a Higher Total Fluid Intake and Water Intake

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Isabelle Guelinckx ◽  
Rizki Pohan ◽  
Romain Monrozier ◽  
Saptawati Bardosono
Keyword(s):  
Drinking Water ◽  
Water Intake ◽  
Fluid Intake ◽  
Total Fluid Intake ◽  
Total Fluid

scholarly journals Harmonized Cross-Sectional Surveys Focused on Fluid Intake in Children, Adolescents and Adults: The Liq.In7 Initiative

2016 ◽  
Vol 68 (Suppl. 2) ◽  
pp. 12-18 ◽  
Author(s):  
Homero Martinez ◽  
Isabelle Guelinckx ◽  
Jordi Salas-Salvadó ◽  
Joan Gandy ◽  
Stavros A. Kavouras ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Water Intake ◽  
Fluid Intake ◽  
Major Contributor ◽  
Adequate Intake ◽  
Total Fluid Intake ◽  
Cross Sectional ◽  
Increase Water Intake ◽  
Adolescents And Adults ◽  
Total Fluid

Objective: To assess the intake of water and all other beverages in children, adolescents and adults. Methods: Three thousand six hundred eleven children (8 ± 2 years), 8,109 adolescents (13 ± 2 years) and 16,276 adults (40 ± 14 years) (47% men) were recruited in 15 cross-sectional surveys (liquid intake across 7 days, Liq.In7 study) and completed a 7-day fluid-specific record to assess total fluid intake (TFI), where TFI was defined as the sum of drinking water and other type of beverages. Results: The median TFI was 1.2, 1.2 and 1.8 liters/day in children, adolescents and adults respectively, with important differences observed between countries. Only 39% of children, 25% of adolescents and 51% of adults met the European Food Safety Authority adequate intake (AI) recommendations of water from fluids. In the surveys of Spain, France, Belgium, Germany, Turkey, Iran, Indonesia and China, water was the major contributor (47-78%) to TFI. In the adult surveys of UK, Poland, Japan and Argentina, hot beverages were the highest contributor to TFI. The fluid intake of children and adolescents in Mexico, Brazil, Argentina and Uruguay was characterized by a contribution of juices and sweet beverages that was as important as the contribution of water to TFI. Conclusion: Given that a relatively high proportion of subjects, especially children and adolescents, failed to meet the recommended AI of water from fluids and that water intake was not the highest contributor to TFI in all countries, undertaking actions to increase water intake are warranted.

Abstract P198: Biphasic And Sex-dependent Roles Of The Prorenin Receptor In The Rostral Ventrolateral Nucleus In Mice Subjected To Deoxycorticosterone Acetate-salt Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Pablo Nakagawa ◽  
Daniel Brozoski ◽  
Natalia M Mathieu ◽  
Ko-Ting Lu ◽  
Javier Gomez ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Urinary Sodium Excretion ◽  
Protective Role ◽  
Salt Treatment ◽  
Deoxycorticosterone Acetate ◽  
Prorenin Receptor ◽  
Ventrolateral Nucleus ◽  
Salt Hypertension

The brain renin angiotensin system (RAS) regulates blood pressure (BP) and autonomic function. However, it remains unclear how and where angiotensin II (Ang II) is generated in conditions eliciting brain RAS overactivation including deoxycorticosterone acetate (DOCA)-salt hypertension (HT). In several tissues, the activation of prorenin requires its binding to the prorenin receptor (PRR). New evidence from this study indicates that prorenin and PRR are co-expressed in the proximity to the rostral ventrolateral nucleus (RVL), an anatomical brain region that controls sympathetic nerve activity. Therefore, we hypothesized that selective ablation of PRR targeting the RVL attenuates BP increase due to DOCA-salt. PRR ablation was targeted to the RVL by stereotactic microinjections of adeno-associated virus (AAV) expressing Cre recombinase-mCherry in PRR-flox mice (PRR RVL-KO ). AAV mCherry was used as control virus (WT). A pressor response to L-glutamate in the injection site served as confirmatory stereotactic target hit. RVL-targeted ablation of PRR resulted in lower BP responses to DOCA-salt in females (WT=115±3 vs KO=104±4 mmHg; p <0.05; n=8), but not males (n=5-8), only during the first 3 days of DOCA-salt treatment. However, at day 13 of DOCA-salt treatment, female PRR RVL-KO unexpectedly exhibited exaggerated increase in systolic BP (WT=149±3 vs KO=163±3 mmHg; p =0.004; n=8) and pulse pressure (WT=31±4 vs KO=45±4 mmHg; p =0.02; n=8) when compared to control. Next, mice were challenged with an intraperitoneal hypertonic saline injection equivalent to 10% of their body weight followed by 4 hours of urine collection. Urinary sodium excretion in female PRR RVL-KO was significantly lower when compared to WT ( p <0.05). These data indicate that the role of PRR in the RVL is sex-dependent and biphasic. That is, PRR contributes to the pressor response during the initial stage of DOCA-salt HT in females, presumably by facilitating the generation of angiotensin peptides in the RVL, while it plays a protective role by promoting renal sodium excretion and preventing elevation of systolic BP during the maintenance stage of DOCA-salt HT. This study suggests that distinct PRR expressing cell populations might elicit diverging physiological functions within the RVL.

Abstract 020: Physiological Significance of Angiotensin AT 1A Receptors in Vasopressin-producing Cells of the Supraoptic Nucleus

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Danny W Linggonegoro ◽  
Jeremy A Sandgren ◽  
Kristin E Claflin ◽  
Katherine J Perschbacher ◽  
Jonathan Ni ◽  
...  
Keyword(s):  
Fluid Intake ◽  
Sodium Intake ◽  
Urine Volume ◽  
Renin Angiotensin System ◽  
Normal Serum ◽  
Serum Osmolality ◽  
Angiotensin System ◽  
Elevated Activity ◽  
Bac Transgene ◽  
The Brain

Low-renin and salt-sensitive forms of hypertension are characterized by elevated activity of the brain renin-angiotensin system and secretion of arginine vasopressin (AVP). While angiotensin in the brain is a known stimulant of AVP secretion through its AT 1 receptor, the localization of relevant AT 1 receptors remains unclear. We tested whether AT 1A receptors localized to AVP-producing cells are important for AVP secretion. To examine AVP and AT 1A co-localization, mice expressing Cre-recombinase via the AVP gene (AVP-Cre) were bred with mice expressing a conditional red fluorescent ROSA-stop flox -tdTomato construct and GFP via an AT 1A BAC transgene. Dual-fluorescent cells were detected in supraoptic nuclei (SON) but not paraventricular nuclei. Mice lacking AT 1A specifically in AVP-producing cells (AT 1A AVP-KO ) were then generated by breeding AVP-Cre mice with mice harboring a conditional endogenous AT 1A gene. AT 1A AVP-KO mice exhibited normal serum (littermate n=13, 353±69 vs AT 1A AVP-KO n=7, 207±37 pg/mL, p=NS) and urine (n=26, 145±33 vs n=11, 170±54 pg/mL, p=NS) copeptin (the stable C-terminal fragment of AVP) as well as hematocrit (n=14, 46.3±0.7 vs n=7, 47.5±1.3 %, p=NS) despite increased serum osmolality (n=33, 324±1.3 vs n=19, 330±1.6 mOsm/kg, p<0.01), supporting a role for AT 1A in AVP-producing cells in modulating the osmotic control of AVP release. Systolic blood pressure (SBP) (n=18, 109±1.3 vs n=5, 107±1.2 mmHg), urine volume (n=27, 1.1±0.1 vs n=12, 0.9±0.2 mL/d), and fluid intake (n=27, 4.0±0.2 vs n=12, 3.9±0.2 mL/d) were all normal (p=NS) in AT 1A AVP-KO mice. Two-bottle choice between water and escalating concentrations of NaCl uncovered minor alterations in sodium intake behavior. Serum osmolality (n=22, 336±2 vs n=9, 333±3 mOsm/kg), SBP (n=23, +10.4±2.1 vs n=8, +12.9±2.0 mmHg), urine output (n=23, +12.7±0.8 vs n=9, +12.7±1.5 g/day), and fluid intake (n=23, +16.2±1.3 vs n=9, +14.8±2.5 mL/day) all increased normally (p=NS) in response to deoxycorticosterone acetate (DOCA)-salt treatment. Collectively these data support a role for AT 1A receptors, localized specifically to AVP-expressing cells of the SON, in the normal osmotic control of AVP secretion.

Extreme Variation of Nutritional Composition and Osmolality of Commercially Available Carbohydrate Energy Gels

2015 ◽  
Vol 25 (5) ◽  
pp. 504-509 ◽  
Author(s):  
Xuguang Zhang ◽  
Niamh O’Kennedy ◽  
James P. Morton
Keyword(s):  
Fluid Intake ◽  
Energy Content ◽  
Sugar Content ◽  
Nutritional Composition ◽  
Sports Nutrition ◽  
Free Sugar ◽  
Total Fluid Intake ◽  
Extreme Variation ◽  
Serving Size ◽  
Total Fluid

The provision of exogenous carbohydrate (CHO) in the form of energy gels is regularly practiced among endurance and team sport athletes. However, in those instances where athletes ingest suboptimal fluid intake, consuming gels during exercise may lead to gastrointestinal (GI) problems when the nutritional composition of the gel is not aligned with promoting gastric emptying. Accordingly, the aim of the current study was to quantify the degree of diversity in nutritional composition of commercially available CHO gels intended for use in the global sports nutrition market. We surveyed 31 product ranges (incorporating 51 flavor variants) from 23 brands (Accelerade, CNP, High5, GU, Hammer, Maxim, Clif, USN, Mule, Multipower, Nectar, Carb-Boom, Power Bar, Lucozade, Shotz, TORQ, Dextro, Kinetica, SiS, Zipvit, Maxifuel, Gatorade and Squeezy). Gels differed markedly in serving size (50 ± 22 g: 29–120), energy density (2.34 ± 0.7 kcal/g: 0.83–3.40), energy content (105 ± 24 kcal: 78–204), CHO content (26 ± 6 g: 18–51) and free sugar content (9.3 ± 7.0 g: 0.6–26.8). Most notably, gels displayed extreme variation in osmolality (4424 ± 2883 mmol/kg: 303–10,135) thereby having obvious implications for both GI discomfort and the total fluid intake likely required to optimize CHO delivery and oxidation. The large diversity of nutritional composition of commercially available CHO gels illustrate that not all gels should be considered the same. Sports nutrition practitioners should therefore consider the aforementioned variables to make better-informed decisions regarding which gel product best suits the athlete’s specific fueling and hydration requirements.

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