Abstract P316: Angiotensin-(1-7) Contributes to the Insulin-sensitizing Effects of Renin-angiotensin System Blockade in High Fat Fed Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Amy C Arnold
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Whole Body ◽  
High Fat ◽  
Angiotensin System ◽  
Renin Angiotensin

Angiotensin-converting enzyme (ACE) inhibitors reduce body weight, lower blood pressure, and improve glucose homeostasis in animal models of the cardiometabolic syndrome. These effects are generally attributed to a reduction in angiotensin (Ang) II formation; however, these therapies also increase circulating levels of Ang-(1-7), a peptide with direct anti-hypertensive and insulin-sensitizing effects. In this study, it was hypothesized that endogenous Ang-(1-7) generation contributes to the beneficial cardiometabolic effects of ACE inhibition. To test this hypothesis, diet-induced obesity was produced in adult male C57BL/6J mice by placing them on a 60% high fat diet for 11 weeks. The Ang-(1-7) mas receptor antagonist A779 (400 ng/kg/min) or saline was given after 8 weeks of the high fat diet by subcutaneous osmotic mini-pumps. Immediately following mini-pump implantation, mice received water containing the ACE inhibitor captopril (50 mg/L) or plain tap water. Hyperinsulinemic (4 mU/kg/min) euglycemic clamps were performed in conscious, unrestrained vehicle (n=6), captopril (n=6), or captopril plus A779 (n=13) mice at the end of the 3-week treatment period. Blood pressure was measured via an indwelling carotid artery catheter connected to a transducer on the morning of the clamp. Captopril reduced body weight (28±2 vs. 41±2 g vehicle; p=0.001), lowered blood pressure (systolic: 109±6 vs.144±7 mmHg vehicle; p=0.003), and improved whole-body insulin sensitivity (steady-state glucose infusion rate: 31±4 vs. 16±2 mg/kg/min; p=0.008) in high-fat fed mice. Mas receptor antagonism with A779 attenuated the improvement in insulin sensitivity produced by captopril in high fat fed mice (23±2 mg/kg/min; p=0.042). There was no effect of A779 on the weight loss (32±2 g) or blood pressure lowering effects (111±7 mmHg) of captopril. These findings suggest that the improvement in insulin sensitivity produced by ACE inhibition is at least partly mediated by Ang-(1-7) pathways, and provide new insight into potential mechanisms involved in renin-angiotensin system blockade.

Abstract P198: Increased Urinary Angiotensinogen Reflects Intrarenal Renin-angiotensin System Activation in High Fat Diet Induced-type 2diabetic Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Virginia Reverte ◽  
Diego Castro Musial ◽  
Michael R Gallaty ◽  
Carla B Rosales ◽  
Alberto J Parra-Vitela ◽  
...  
Keyword(s):  
Body Weight ◽  
Renal Injury ◽  
High Fat Diet ◽  
Renin Angiotensin System ◽  
High Fat ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Type 2 Dm ◽  
Intrarenal Ras

Obesity is a risk factor for diabetes mellitus (DM) and patients with DM are often hypertensive and exhibit inappropriate activation of the intrarenal renin-angiotensin system (RAS), which increases the risk for diabetic nephropathy and progression to chronic kidney disease. Enhanced intrarenal AGT levels contribute to increased intrarenal Angiotensin II levels. To examine the role of an activated RAS in DM, we measured urinary AGT along with albuminuria and other metabolic parameters in high fat diet induced-type 2 DM mice. Immediately after weaning, male C57BL/6J mice (N=18) were fed either a normal fat diet (18 % Kcal from fat; CT mice) or high fat diet (42.0 % Kcal from fat; HF mice) for 24 wk. Body weight (BW), food intake, and systolic blood pressure (SBP) by telemetry, were measured weekly. Glucose tolerance test (GTT) and homeostasis model assessment index of insulin resistance (HOMA-IR) were further assayed. At wks 0, 12, and 24 on dietary regimen, measurements of albuminuria and uAGT by ELISA were used as markers of renal injury and intrarenal RAS activation, respectively. Body weight increased by 140% in HF mice compared to 66 % in CT mice (from 18±0.5 to 44±1.4 g and 17±0.6 to 28±0.6 g, respectively) with no differences in daily energy intake (15.02±1.3 kcal/day and 15.4±0.8 kcal/day). Plasma glucose, area under curve (AUC) of GTT, and HOMA-IR were significantly increased in HF mice (121± 6mg/dL; 32,865±6,222; 5±1) compared to CT mice (220± 27mg/dL; 55,549±4,611; 54±9). In HF mice, SBP was augmented by wk 10 compared to CT mice (126±5 vs. 113±1 mmHg; P<0.05). Interestingly, no differences in albuminuria were found between HF and CT mice either at wk 12(50±13 vs. 40±6 ug/day) or at wk 24 (57±7 vs. 43±3 ug/day). However, uAGT excretion was increased by wk 24 in HF mice but not in CT mice ( wk 0 : 4±1.5 vs. 4±1.5ng/day; wk 12 : 4.6±2.3 vs. 2.3±0.9 ng/day; wk 24 : 11.8±2.9 vs. 3.9±0.3 ng/day; P<0.05). During HF diet induced-type 2 DM, the elevation of uAGT reflects the increase of intrarenal RAS which may contribute to the development of renal injury.

Abstract 018: Neuronal (Pro)renin Receptor Deletion Prevents High-fat Diet Induced High Blood Pressure and Type II Diabetes

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Caleb J Worker ◽  
Wencheng Li ◽  
Yumei Feng
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Angiotensin Ii ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Fasting Blood Glucose ◽  
Renin Angiotensin System ◽  
High Fat

We recently reported that the (pro)renin receptor (PRR) is a key component of the brain renin-angiotensin system, mediating the majority of Ang II formation, and plays a pivotal role in the development of hypertension. Its importance in obesity-related metabolic syndrome is, however, unknown. We hypothesize that brain PRR plays a regulatory role in high-fat diet (HFD) induced metabolic syndrome. To test our hypothesis, neuron-specific PRR knockout (PRRKO) mice and wildtype (WT) littermates were fed with either HFD (60% calories from fat) or normal fat chow (NFD, 10% calories from fat) with matching calories for 16 weeks. Weekly body weight (BW) and monthly fasting blood glucose (FBG) measurements were recorded and end point glucose tolerance (GTT) and insulin sensitivity tests (IST) were performed. Blood pressure (BP) was recorded using radiotelemetry in conscious free moving mice. We observed no difference in BW or food intake between genotypes in either HFD or NFD. The baseline BP and heart rate (HR) were similar between PRRKO and WT mice; however, following 16 weeks HFD the BP (101±6 vs. 111±3 mmHg, P=0.035) and HR (536±12 vs. 578±4 BPM, P=0.046) were significantly lower in PRRKO compared with WT mice. Interestingly, neuronal PRR deletion attenuated the elevation of FBG (127.12±10.46 vs. 167.77±16.57 mg/dl, P=0.039) induced by HFD. Glucose tolerance was significantly improved in PRRKO compared with WT following 16 weeks of HFD (AUC: 20557±894 vs. 29994±2976, P=0.006), while there was no difference in the IST between the groups. We also found that HFD mice had higher levels of plasma (pro)renin (9.95±1.83 vs. 2.74± 0.47 ng/ml, P=0.005) and brain angiotensin II (656.8±94.9 vs. 375.3±32.0 pg/g, P=0.02), as well as higher cardiac (ΔHR to propranolol: -150±6 vs. -82±15 bpm , P=0.0054) and vasomotor (ΔBP to chlorisondamine: -44±3 vs. -22±3 mmHg, P=0.0004) sympathetic tone, suggesting that the HFD-induced rise in BP is sympathetically mediated and associated with elevation of brain angiotensin II. Our data indicates that PRR deletion in the neurons protects against glucose intolerance and BP elevation in HFD mice with no effect on insulin sensitivity or body weight. We conclude that neuronal PRR plays a role in the development of obesity-related metabolic syndrome.

scholarly journals Renin-angiotensin System (RAS)-mediated Antiobesity and Antihypertensive Effects of Korean Traditional Soybean Paste (Doenjang) in Rat Model of Diet-induced Obesity (P08-097-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Hayoung Woo ◽  
Jung Eun Park ◽  
Youn-soo Cha
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
High Fat Diet ◽  
Health Benefits ◽  
Renin Angiotensin System ◽  
Serum Chemistry ◽  
Table Salt ◽  
High Fat ◽  
Angiotensin System ◽  
Renin Angiotensin

Abstract Objectives Hypertension is becoming more prevalent and one of the main cause is found in the increase of excessive dietary sodium intake. It is also risk factors for cardiovascular and kidney disease. Korean Traditional Fermented Food, doenjang, is made with high salt, so many of them are thinking that there is a lot of relation to hypertension despite reporting many health benefits. Our previous studies reported that doenjang have been associated effect of anti-obesity in human and animal study. Therefore, we expected that doenjang may have different effects on blood pressure and lipid metabolism compared to same concentrations of salt. Methods In this study, Sprague-Dawley rats divided into four groups, normal diet (ND), high fat diet (HD), high fat diet with 8% table salt (HDS), high fat diet with Doenjang contains 8% table salt (HDJ) for 13 weeks. The systolic blood pressure (SBP), serum chemistry, Na+ and K+ concentrations, liver and renal gene expressions were measured. Results Doenjang decreased systolic blood pressure (SBP), body weight and hepatic lipids. Serum chemistry, leptin and aldosterone levels were increased in HD and HDS groups while decreased in HDJ group. Results from analysing feces and urine, Na+, Ca+ and K+concentrations were changed by Doenjang. Furthermore, fatty acid synthesis-related genes expression was decreased in liver and downregulated the renin, AT1 receptor and ACE in renal cortex of doenjang treatment group. Conclusions These results suggest that doenjang may have anti-obesity and anti-hypertension through regulation of the renin angiotensin system. We believed that it is an important result of demonstrating that doenjang has health benefits regardless of salt content. Funding Sources This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (No. 2018R1A2B6006477).

Abolition of long-term vascular influence of renin-angiotensin system

1990 ◽  
Vol 259 (2) ◽  
pp. H543-H553
Author(s):  
R. D. Randall ◽  
B. G. Zimmerman
Keyword(s):  
Blood Pressure ◽  
Vascular Tissue ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Ang Ii ◽  
Flow Measurements ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Normal Controls

Rabbits were bilaterally nephrectomized for 24 h or received an angiotensin-converting enzyme (ACE) inhibitor chronically (5 days) before an acute experiment. Conductance responses to sympathetic nerve stimulation (SNS) (0.25, 0.75, and 2.25 Hz) and norepinephrine (NE) administration (0.2, 0.6, and 1.8 micrograms ia) were determined from simultaneous blood pressure and iliac blood flow measurements. Conductance responses to SNS were significantly reduced in nephrectomized (44, 26, and 20%) and chronic ACE inhibition (39, 31, and 24%) groups compared with normal controls, whereas conductance responses to NE were unchanged. Continuous infusion of angiotensin II (ANG II) for 24 h restored the depressed responses to SNS in nephrectomized and chronic ACE inhibition groups compared with normal controls but did not change conductance responses to NE. Acute ACE inhibition did not affect the conductance responses to SNS or NE compared with controls. Vascular tissue ACE activity was inhibited to a similar degree (50%) in both acute and chronic ACE inhibition groups compared with normal rabbits. Sodium depletion increased the conductance responses to SNS (30 and 24% at 0.25 and 0.75 Hz, respectively), but responses to NE were not affected. Chronic ACE inhibition significantly attenuated the conductance responses to SNS and slightly decreased responses to NE in sodium-depleted rabbits. Thus, in the anesthetized rabbit, the renin-angiotensin system potentiates the effect of SNS, presumably by ANG II acting at a prejunctional site, and this effect of ANG II appears to be long term in nature. Therefore, the renin-angiotensin system exerts a physiological role in the control of blood pressure in addition to the ability of this system to support arterial pressure in pathophysiological states.

scholarly journals The Effect of Angiotensin-Converting Enzyme Inhibition Using Captopril on Energy Balance and Glucose Homeostasis

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4114-4123 ◽  
Author(s):  
Annette D. de Kloet ◽  
Eric G. Krause ◽  
Dong-Hoon Kim ◽  
Randall R. Sakai ◽  
Randy J. Seeley ◽  
...  
Keyword(s):  
Body Weight ◽  
Glucose Tolerance ◽  
Angiotensin Converting Enzyme ◽  
High Fat Diet ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
High Fat ◽  
Angiotensin System ◽  
Converting Enzyme Inhibition

Abstract Increasing evidence suggests that the renin-angiotensin-system contributes to the etiology of obesity. To evaluate the role of the renin-angiotensin-system in energy and glucose homeostasis, we examined body weight and composition, food intake, and glucose tolerance in rats given the angiotensin-converting enzyme inhibitor, captopril (∼40 mg/kg · d). Rats given captopril weighed less than controls when fed a high-fat diet (369.3 ± 8.0 vs. 441.7 ± 8.5 g after 35 d; P &lt; 0.001) or low-fat chow (320.1 ± 4.9 vs. 339.8 ± 5.1 g after 21 d; P &lt; 0.0001). This difference was attributable to reductions in adipose mass gained on high-fat (23.8 ± 2.0 vs. 65.12 ± 8.4 g after 35 d; P &lt; 0.0001) and low-fat diets (12.2 ± 0.7 vs. 17.3 ± 1.3 g after 21 d; P &lt; 0.001). Rats given captopril ate significantly less [3110.3 ± 57.8 vs. 3592.4 ± 88.8 kcal (cumulative 35 d high fat diet intake); P &lt; 0.001] despite increased in neuropeptide-Y mRNA expression in the arcuate nucleus of the hypothalamus and had improved glucose tolerance compared with free-fed controls. Comparisons with pair-fed controls indicated that decreases in diet-induced weight gain and adiposity and improved glucose tolerance were due, primarily, to decreased food intake. To determine whether captopril caused animals to defend a lower body weight, animals in both groups were fasted for 24 h and subsequently restricted to 20% of their intake for 2 d. When free food was returned, captopril and control rats returned to their respective body weights and elicited comparable hyperphagic responses. These results suggest that angiotensin-converting enzyme inhibition protects against the development of diet-induced obesity and glucose intolerance.

scholarly journals Dysregulation of the Renin-Angiotensin System and Cardiometabolic Status in Mice Fed a Long-Term High-Fat Diet

2019 ◽  
Vol 25 ◽  
pp. 6605-6614 ◽  
Author(s):  
Nana Jin ◽  
Yu Wang ◽  
Lin Liu ◽  
Feng Xue ◽  
Tingbo Jiang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Renin Angiotensin System ◽  
High Fat ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Açaí seed extract prevents the renin-angiotensin system activation, oxidative stress and inflammation in white adipose tissue of high-fat diet–fed mice

2020 ◽  
Vol 79 ◽  
pp. 35-49 ◽  
Author(s):  
Izabelle Barcellos Santos ◽  
Graziele Freitas de Bem ◽  
Cristiane Aguiar da Costa ◽  
Lenize Costa Reis Marins de Carvalho ◽  
Amanda Faria de Medeiros ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Renin Angiotensin System ◽  
Seed Extract ◽  
High Fat ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
System Activation

Activation of the systemic and adipose renin-angiotensin system in rats with diet-induced obesity and hypertension

2004 ◽  
Vol 287 (4) ◽  
pp. R943-R949 ◽  
Author(s):  
Carine M. Boustany ◽  
Kalyani Bharadwaj ◽  
Alan Daugherty ◽  
David R. Brown ◽  
David C. Randall ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Body Weight Gain ◽  
Plasma Concentrations ◽  
Renin Angiotensin System ◽  
Sprague Dawley ◽  
High Fat ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Arterial Blood

In obesity-related hypertension, activation of the renin-angiotensin system (RAS) has been reported despite marked fluid volume expansion. Adipose tissue expresses components of the RAS and is markedly expanded in obesity. This study evaluated changes in components of the adipose and systemic RAS in diet-induced obese hypertensive rats. RAS was quantified in adipose tissue and compared with primary sources for the circulating RAS. Male Sprague-Dawley rats were fed either a low-fat (LF; 11% kcal as fat) or moderately high-fat (32% kcal as fat) diet for 11 wk. After 8 wk, rats fed the moderately high-fat diet segregated into obesity-prone (OP) and obesity-resistant (OR) groups based on their body weight gain (body weight: OR, 566 ± 10; OP, 702 ± 20 g; P < 0.05). Mean arterial blood pressure was increased in OP rats (LF: 97 ± 2; OR: 97 ± 2; OP: 105 ± 1 mmHg; P < 0.05). Quantification of mRNA expression by real-time PCR demonstrated a selective increase (2-fold) in angiotensinogen gene expression in retroperitoneal adipose tissue from OP vs. OR and LF rats. Similarly, plasma angiotensinogen concentration was increased in OP rats (LF: 390 ± 48; OR: 355 ± 24; OP: 530 ± 22 ng/ml; P < 0.05). In contrast, other components of the RAS were not altered in OP rats. Marked increases in the plasma concentrations of angiotensin peptides were observed in OP rats (angiotensin II: LF: 95 ± 31; OR: 59 ± 20; OP: 295 ± 118 pg/ml; P < 0.05). These results demonstrate increased activity of the adipose and systemic RAS in obesity-related hypertension.

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