bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salt‐deficient diet does not attenuate the development of slowly progressive ANG II‐dependent hypertension in Cyp1a1‐Ren2 transgenic rats
Authors: Collins Amy E , Howard Catherine G , Mitchell Kenneth D 
Published: June 2021

The present study was performed to determine the effects of dietary salt restriction on conscious systolic blood pressure (SBP), and 24‐hour urine flow and urinary sodium and protein excretion in Cyp1a1‐Ren2 rats with slowly progressive ANG‐II dependent hypertension. Adult male Cyp1a1‐Ren2 rats (n=5–6/group) were fed either a normal salt (0.6%) or salt‐deficient diet (<0.01%) containing indole‐3‐carbinol (I3C; 0.15%, wt/wt) to induce slowly progressive ANG II‐dependent hypertension. Both normal salt and salt‐deficient groups fed an I3C‐containing diet showed increases in SBP by day 4 of treatment (134±3 to 162±3 and 147±4 to 160±3 mmHg, respectively, P<0.001) and reached similar SBP levels by day 16 (207±8 vs. 194±7 mmHg, NS). Induced rats on salt‐deficient diet exhibited markedly reduced 24‐hour urinary sodium excretion (74.4±15.8 to 0.20±0.07 mEq/day, P<0.001) and urine output (10.2±1.3 vs. 18.8±3.5 mL/day, P<0.05. Urinary protein excretion increased similarly in response to I3C administration regardless of dietary salt intake (7.5±0.8 to 25.2±4.4, and 6.6±0.3 to 35.7±5.7 mg/d, respectively, P<0.05). These findings demonstrate that dietary salt restriction does not attenuate the development of slowly progressive ANG II‐dependent hypertension or the associated proteinuria in Cyp1a1‐Ren2 transgenic rats.Support: NHLBI, Tulane COBRE in Hypertension and Renal Biology.
Tumor necrosis factor alpha activates RhoA and decreases NO synthase type 3 expression in rat thick ascending limbs
Authors: Ramseyer Vanesa Daniela , Hong Nancy , Garvin Jeffrey Lawrence 
Published: June 2021

NO produced by NO synthase type 3 (NOS3) decreases thick ascending limb (THAL) NaCl reabsorption and induces natriuresis. Tumor necrosis factor alpha (TNF) stimulates RhoA GTPase and Rho kinase (ROCK) and decreases NOS3 expression in endothelial cells. Therefore, we hypothesized that TNF decreases NOS3 expression via Rho/ROCK in rat THALs. We measured: 1) NOS3 expression by Western blot and 2) RhoA activity by ELISA. Treatment of THAL primary cultures with 1 nM TNF for 24 hrs decreased NOS3 expression by 54 ± 4% (n= 6, p<0.001). Treatment with TNF for 10 min increased RhoA activity from 0.520 ± 0.038 OD to 0.816 ± 0.090 (Δ= 60±23%, p<0.03). Blockade of RhoA with 0.05 ug/mL C3 exoenzyme inhibited TNF‐induced reductions in NOS3 expression by 30 ± 9% (n=7, p<0.02) while C3 exoenzyme alone did not change NOS3 expression. Blockade of ROCK with 10 μM H‐1152 blunted TNF‐mediated reductions in NOS3 expression by 66 ± 15 % (n=6 p<0.001) while H‐1152 alone did not affect NOS3 expression. Simultaneous blockade of RhoA and ROCK were not additive (inhibition of TNF's effect = 56 ± 19 % n=5, p<0.05). We conclude that: 1) TNF decreases NOS3 expression in THALs; and 2) this effect is partially mediated by Rho/ROCK. Blockade of Rho/ROCK may improve renal function in hypertension by preventing TNF‐induced decreases in NOS3 expression.Sources of funding: NIH HL 028982 to J.L.G. and AHA 11PRE7510005 to V.D.R
Inhibition of KV7 channels causes rat renal vasoconstriction in vivo
Authors: Sorensen Charlotte Mehlin , Holstein-Rathlou Niels-Henrik , Salomonsson Max 
Published: June 2021

We investigated the possible role of KV7 (KCNQ)‐channels in the control of rat renal vascular hemodynamics. We also investigated whether this family of K+ channels participated in the acetylcholine (ACh) mediated renal vasodilation.We measured renal blood flow (RBF) in vivo in Sprague Dawley rats using an ultrasonic flow probe. Basal RBF was 6.0 ± 0.38 ml/min (n=5). Intrarenal infusion of XE991 (a potent blocker of KV7.1‐7.5) at rates of 0.6 nmol/min and 6 nmol/min did not affect RBF (n=5). However, intrarenal infusion of XE991 for 1.5 min at rates of 15 nmol/min and 30 nmol/min (estimated plasma concentrations ~2.5 μM and 5 μM, respectively) significantly decreased RBF by 2.2 ± 0.6 % and 3.1 ± 0.8 %, respectively (n=5). After 4 min XE991 infusion the corresponding RBF decreases were 3.5 ± 0.8 % and 4.6 ± 0.8 %, respectively (n=5). Intrarenal ACh infusion at a rate of 3 nmol/min (estimated plasma concentration ~ 0.5 μM) increased RBF by 26 ± 2.8 % (n=3). Pretreatment with XE991 (30 nmol/min) for 1.5 min did not affect the response to ACh as RBF increased by 28 ± 2.9 % (n=3). In summary, we show that KV7 channels have a potential role in the regulation of renal hemodynamics. Furthermore, we find no indication that these channels play a role in ACh induced renal vasodilation. This study is supported by the Danish National Research Foundation, the Danish Heart Foundation, and the Lundbeck Foundation.
Renal function in T‐type voltage‐gated calcium channel knock‐out mice
Authors: Hansen Pernille B.L. , Andersen Henrik , Cardel Majken , Shin Hee-Sup , Skott Ole , Jensen Boye L. , Bie Peter 
Published: June 2021

T‐type voltage‐gated calcium channels (Cav) are expressed in renal resistance vessels and collecting duct and calcium channels play an essential role in regulation of renal blood flow and glomerular filtration rate. The objective of the present study was to investigate renal function in two T‐type calcium channel knock‐out (KO) mice strains (Cav3.1 and Cav3.2). Continuous recordings of blood pressure (MAP), heart rate and inulin clearance (GFR) were performed in Wt and Cav3.1 and Cav3.2 KO mice using indwelling catheters. The night heart rate was significant lower in Cav3.1 KO compared to Wt with no difference in MAP. GFR was significantly higher in Cav3.2 KO compared to Wt. GFR in Cav3.1 KO were indistinguishable from Wt. No significant difference was observed in water intake, diuresis and electrolyte excretion measured before and after 24 hour water deprivation comparing Wt and Cav3.1 KO mice however a significant increase in sodium excretion rate was observed in both strains after water deprivation. We tested whether the high GFR in Cav3.2 KO was related to an increased contractility of the efferent arteriole in isolated perfused efferent arterioles. However depolarization and endothelin‐1 induced significant and similar constriction in Wt, Cav3.1 and Cav3.2 KO mice. In conclusion, lack of Cav3.1 is associated with a decreased heart rate whereas lack of Cav3.2 T‐type channels is associated with an increased GFR.Research Support: Lundbeck Foundation, The Danish Medical Research Council, The Danish Heart Foundation
Chronic direct renin inhibition with aliskiren normalizes blood pressure and improves renal hemodynamics in Cyp1a1‐Ren2 transgenic rats with ANG II‐dependent malignant hypertension
Authors: Howard Catherine G , Mitchell Kenneth D 
Published: June 2021

The present study determined if direct renin inhibition with aliskiren can normalize blood pressure and improve renal hemodynamics in Cyp1a1‐Ren2 transgenic rats with ANG II‐dependent malignant hypertension. Adult male Cyp1a1‐Ren2 rats (n=6) received 0.3% indole‐3‐carbinol (I3C) in the diet to induce ANG II‐dependent malignant hypertension [systolic blood pressure (SBP): 137±2 to 222±5 mmHg, P<0.001)]. Subsequent chronic renin inhibition with aliskiren (60 mg/kg/d, sc) during continued I3C administration normalized SBP within one day (102±3 mmHg, P<0.001) and maintained SBP at normotensive levels for 10 days (135±2 mmHg, P<0.001). Pentobarbital sodium anesthetized rats treated chronically with aliskiren exhibited lower MAP (138±3 vs. 187±6 mmHg, P<0.001) and renal vascular resistance (19.4±0.8 vs. 39.8±2.3 mmHg/ml/min.g, P<0.001), and increased renal plasma flow (3.8±0.2 vs. 2.4±0.1 ml/min.g, P<0.001) compared to untreated hypertensive rats (n=6). Glomerular filtration rates were comparable in the two groups of rats. The present findings demonstrate that chronic renin inhibition with aliskiren is highly effective in normalizing the elevated arterial blood pressure and in improving renal hemodynamics in ANG II‐dependent malignant hypertension.Support: NHLBI, Tulane COBRE in Hypertension and Renal Biology, Novartis Pharma, AHA Greater Southeast Affiliate Predoctoral Fellowship.
Imaging intracellular calcium signals in intact kidney tissue
Authors: Crawford Carol , Hall Andrew M , Peppiatt-Wildman Claire M 
Published: June 2021

Calcium (Ca2+) is an intracellular secondary messenger with multiple important physiological roles; disturbances in intracellular Ca2+ homeostasis have been implicated in the pathogenesis of various kidney diseases. We have recently demonstrated that multiphoton microscopy can be used to image a range of intracellular signals in ex vivo rat kidney preparations such as tissue slices [1, 2] and isolated perfused organs [3].Here, we demonstrate that the tissue slice model can be used to load established Ca2+ indicators into both tubular and endothelial cells in the kidney. Kidney slices (200 μm thick) were obtained from adult, male sprague dawley rat kidneys (following cervical dislocation) and maintained in a physiological saline solution, bubbled with 95% O2/5% CO2. Loading of exogenous Ca2+ sensitive dyes (Fluo4, Rhod‐2, Fura Red) was achieved ex vivo by using a re‐circulating perfusion system. Confocal microscopy was used to image Ca2+ loading in the renal medulla, and to record changes in signal in response to physiological stimuli, i.e. ATP, Angiotensin II.We believe that the application of these imaging techniques have much potential to enhance understanding of the roles of intracellular Ca2+ signalling in renal physiology and pathophysiology.Research supported by the Medical Research Council
Apurinic/apyrimidinic endonuclease 1 (APE1) inhibits oxidative stress in gastric epithelial cells during H. pylori infection through binding and inhibition of Rac1
Authors: Chattopadhyay Ranajoy , Das Soumita , Hall Emily , Ablack Amber , Ernst Peter , Crowe Sheila 
Published: June 2021

BackgroundWe have shown that H. pylori (Hp) infection of gastric epithelial cells (GEC) increases reactive oxygen species (ROS) and induces APE1 expression. Rac1 and NAPDH oxidase contribute to Hp‐mediated oxidative stress. Thus, we hypothesized that APE1 regulates Rac1 and NADPH oxidase (Nox1).MethodsAfter Hp infection, superoxide was measured by luminol oxidation in stable APE1 deficient AGS cells (shRNA) and wild‐type (WT) cells. Diphenylene iodonium (DPI) and NSC23766 were used to inhibit NADPH oxidase and Rac1 respectively. Rac1 activity was assessed by GST‐PBD pulldown assay. Rac1‐APE1 interaction was measured by co‐immunoprecipitation and confocal microscopy. Nox1 and APE1 mRNA levels in patient gastric tissues were measured by RT‐ PCR.ResultsIncreased ROS, Rac1 activity and Nox1 were measured in shRNA cells compared to WT after Hp infection. APE1 overexpression decreased Hp induced Rac1 activation as well as Nox1 expression. N‐terminal Lys mutation of APE1 reduced the interaction with Rac1. Mutant APE1 overexpression resulted in increased ROS accumulation and Nox1 expression after Hp infection. Both Nox1 and APE1 mRNA levels were elevated in GEC from Hp infected patient tissues.ConclusionsAPE1 acts as a negative regulator of ROS accumulation due to Hp infection by inhibiting Rac1 and Nox1. (Research Support, R01DK061769‐09).
CFTR‐dependent HCO3‐ defect, cause of viscous mucus in distal intestinal obstruction syndrome (DIOS)?
Authors: Yang Ning , Quinton Paul M. 
Published: June 2021

Background & AimDistal intestinal obstruction syndrome (DIOS) is a condition unique to Cystic Fibrosis, which is due to the accumulation of abnormally viscous mucus in the intestinal tract. However, the pathogenesis of DIOS has not been determined. This study is to test our hypothesis that the CFTR‐dependent HCO3− defect is a cause of more viscous mucus in DIOS.MethodsSegments of distal small intestine (ileum) and distal colon from CL57B1/6 WT mice were incubated with stimulants in vitro in either NaCl (no HCO3−) or NaHCO3 (with HCO3−) Ringers solution. Mucus samples were collected from the incubated intestines and analyzed by a spot tracking method for mucus viscosity. pH‐stat and Ussing chamber techniques were used to measure HCO3− secretion.ResultsAfter stimulating with 5‐HT (10 μM) and PGE2 (1 μM), we found that the mucus viscosity from both ileal and distal colonic sacs incubated with HCO3− Ringer solution was significantly lower than the mucus from sacs incubated in Ringer solution without HCO3−, indicating that HCO3− secretion decreased the mucus viscosity in both the mouse ileum and distal colon. However, we found that CFTR inhibitor, glyH‐101 (20 μM) significantly inhibited 5‐HT and PGE2‐induced HCO3− secretion only in the ileum, not in the distal colon, suggesting that HCO3− secretion in the ileum is CFTR‐dependent.SummaryThe CFTR‐dependent HCO3−defect in the distal small intestine is probably a cause of the more viscous mucus in DIOS.
1,25‐Dihydroxyvitamin D Enhances Alveolar Fluid Clearance by Up‐Regulating the Expression of Epithelial Sodium Channels
Authors: Nie Hongguang , Yu Tong , Nie Zhuang , Ji Honglong , Li Yan Chun 
Published: June 2021

PurposeVitamin D is implicated in the pathogenesis of asthma, acute lung injury and other respiratory diseases. 1,25‐ dihydroxyvitamin D (1,25‐VD), the hormonal form of vitamin D, has been shown to reduce vascular permeability and ameliorate lung edema (Chen SF, et al. 1995). Therefore, we speculate that 1,25‐VD may regulate alveolar Na+ transport via targeting epithelial Na+ channels (ENaC), a crucial pathway for alveolar fluid clearance (AFC).MethodsKM male mice (20~30g) were treated with active vitamin D analogue paricalcitol (daily i.p. injection) for 2 weeks before the in vivo AFC of these mice was measured. Western blotting was used to determine ENaC protein levels in mouse lungs and in human lung H441 epithelial cells treated with 1,25‐VD (20 nM). Whole cell patch‐clamp technique was used to measure ENaC activity in H441 cells.ResultsIn vivo total AFC was 31.9 ± 3.8% in paricalcitol‐treated mice, significantly greater than vehicle‐treated controls (19.7 ± 1.9%, n=10, P < 0.05). Amiloride‐sensitive AFC was increased approximately 50% by paricalcitol. Western blot showed that the expression of γ‐ENaC was significantly elevated in 1,25‐VD‐treated H441 cells and in paricalcitol‐treated mouse lungs. Amiloride‐sensitive Na+currents were greater (184%) in 1,25‐VD‐treated H441 cells compared to vehicle‐treated cells.ConclusionsThese observations suggest that vitamin D augments transalveolar fluid clearance, and vitamin D therapy may potentially be used to ameliorate pulmonary edema.This study was supported by the NSFC (30971181) to HG Nie, and NIH HL87017 to HL Ji.
The Role of the 2‐Pore Domain Potassium Channel Trek‐1 in Regulation of Cytokine Secretion from Alveolar Epithelial Cells
Authors: Schwingshackl Andreas , Teng Bin , Ghosh Manik , Makena Patrudu , Waters Christopher M 
Published: June 2021

Release of inflammatory mediators from epithelial cells contributes to the development of Acute Lung Injury, but the underlying mechanisms are poorly understood. We have previously shown that deficiency of the 2‐pore domain potassium (K2P) channel Trek‐1 resulted in decreased IL‐6 and RANTES secretion and increased MCP‐1 secretion from MLE‐12 cells. The objective of this study was to investigate the mechanisms of TNF‐α‐induced cytokine release from Trek‐1‐deficient alveolar epithelial cells.MethodsWe studied expression of protein kinase C (including its isoforms α, β, μ, δ, θ, λ, μ, and ζ), of JNK and p36 kinase, and of the transcription factor p65/NFκB in Trek‐1 deficient (shRNA) MLE‐12 cells after stimulation with TNF‐α.ResultsTrek‐1‐deficiency resulted in decreased expression of total and phosphorylated PKC after stimulation with TNF‐α. In particular, phosphorylation of the PKC isoforms α, β, μ, δ, θ and μ, but not λ and ζ was decreased in Trek‐1‐deficient cells. TNF‐α caused increased phosphorylation of JNK 1/2/3 and decreased phosphorylation of p38 kinase in Trek‐1 deficient cells. Trek‐1‐deficiency did not affect expression of p65/NFκB after stimulation with TNF‐α.ConclusionTrek‐1 may regulate cytokine secretion from alveolar epithelial cells via PKC‐, JNK‐ and p38‐dependent pathways.This study was supported by NIH grant HL 094366 and the Children's Foundation Research Center.
Reduction of Alveolar Type II Cell Volume in Klotho‐deficient Mice With Premature Aging
Authors: Ravikumar Priya , Bellotto Dennis J. , Kuro-o Makoto , Moe Orson W. , Hsia Connie C.W. 
Published: June 2021

Klotho mitigates aging in multiple organs. Genetic Klotho deficiency (KL−/−) leads to premature senescence, organ degeneration and death. Age‐related airspace enlargement has been reported in the lungs of KL−/− and haplo‐insufficient (KL+/−) mice (Nature 1997;390:45–51). To examine the relationship between Klotho deficiency and lung structure, we performed morphometry on the right lung of 8–12 wk old KL−/− (n=9) and wild type (KL+/+, n=5) mice. Lungs were fixed by tracheal instillation of 2.5% glutaraldehyde (25cmH2O airway pressure). τhb, harmonic mean thickness of diffusion barrier Mean±SD.

Genotype
KL+/+
KL−/−

Body weight (g)
18.9±3.8
10.1±3.9 *

Right lung vol (mL/kg)
25.55±4.21
28.87±8.03

τhb (μm)
0.549±0.028
0.556±0.049

Volume‐to‐lung volume ratio

Alveolar ducts
0.045±0.007
0.056±0.020 †

Septum
0.113±0.019
0.102±0.004

Capillary blood
0.040±0.007
0.036±0.002

Epithelium–type I
0.018±0.003
0.018±0.001

–type II
0.007±0.001
0.005±0.000 *

Interstitium–collagen
0.026±0.004
0.023±0.002

–cell/matrix
0.004±0.001
0.004±0.001

Endothelium
0.018±0.003
0.018±0.001

p≤0.001,
p<0.05 vs. WT.

KL−/− mice were small and frail. Per kg of body weight, volumes and surface areas of the lung and alveolar components were similar to WT except the volume density of alveolar ducts was 24% higher and that of alveolar type II cells 30% lower. We conclude that Klotho deficiency is associated with diminished reservoir of alveolar progenitor cells, which could contribute to premature aging of the lung.Supported by NIH F32 HL103043, RO1 AG19712
Upregulation of TMEM16A Underlies Chronic Hypoxia‐induced Increase of Ca2+‐activated Cl− Current in Pulmonary Arterial Smooth Muscle
Authors: Sun Hui , Xia Yang , Paudel Omkar , Yang Xiao-Ru , Sham James SK 
Published: June 2021

Ca2+‐activated Cl− channels (CaCCs), encoded by TMEM16A, play an important role in the regulation of vascular tone. We have previously observed an increase in CaCC current (ICl.Ca) and TMEM16A expression in pulmonary arterial smooth muscle cells (PASMCs) and tissue of rats with chronic hypoxic pulmonary hypertension (CPHP, 10 ±0.5% O2 for 3–4 weeks). This study aimed to determine whether chronic hypoxia (CH) alters the Ca2+‐or voltage‐dependence of CaCCs in PASMCs, thereby contributes to the enhanced ICl.Ca. Perforated and conventional whole‐cell patch clamp techniques were used to record the caffeine‐induced ICl.Ca and Ca2+ transients simultaneously on fluo 3/AM‐loaded PASMCs, and ICl.Ca evoked by depolarization at constant high Ca2+, respectively. The activation rates of caffeine‐induced ICl.Ca and Ca2+ release were not different between control and hypoxic PASMCs, and their strong correlation was unaltered by CH at both 0 and −80 mV. At 750 nM of [Ca2+]I, the current‐voltage relation exhibited a strong outward rectification in both control and CH cells with similar rectification index (I+60/I−60=8.7±0.5 vs 8.2±0.8, P>0.05). The steady‐state activation curves from both groups were almost overlapped. The time‐dependent activation of ICl.Ca during depolarization, reflecting the voltage‐dependent Ca2+ binding to the channel, were unchanged in hypoxic PASMCs. These results suggest Ca2+‐ or voltage‐dependent properties of CaCC were unaffected by CH. Thus, the enhanced ICl.Ca is mainly attributable to increased channel expression.Supported by grants from NIH and AHA.
Control of sympathetic and phrenic nerve activity by cholinergic mechanisms in the nucleus of the solitary tract (NTS)
Authors: Furuya Werner Issao , Bassi Mirian , Menani José Vanderlei , Colombari Eduardo , Zoccal Daniel Breseghello , de Almeida Colombari Débora Simões 
Published: June 2021

Cholinergic receptors are present in the NTS and acetylcholine (ACH) microinjected into the medial NTS (mNTS) induces hypotension and bradycardia in rats (da Silva et al., 2008; AJP, 295, p R1774). In the present study, we tested the changes in the sympathetic and phrenic nerve activities produced by ACH injected alone or combined with atropine (ATR, muscarinic antagonist) into the mNTS or into the commissural NTS (cNTS). Decorticated arterially‐perfused in situ preparations of male Holtzman rats (60–90 g, n=5–6) were used to record thoracic sympathetic (tSNA) and phrenic nerve (PNA) activities. ACH (10 mM in 60 nL) was injected into the mNTS or cNTS before and 10 min after ATR (17 and 67 mM in 60 nL). Saline was injected as control. ACH into the mNTS reduced the tSNA (−66.1 ± 6.0 % vs. saline: −0.6 ± 3.3 % of baseline) and PNA frequency (−39.7 ± 2.7 % vs. saline: −2.4 ± 2.6 % of baseline), a response attenuated by ATR (67 mM) into the mNTS (tSNA: −29.7 ± 5.2 % and PNA: −12.8 ± 4.6 %, p<0.05). ACH into the cNTS increased PNA frequency (33.1 ± 6.8 %, vs. saline: −6.4 ± 2.7 %), without changing tSNA. ATR (17 mM) into the cNTS reduced the ACH‐induced increase in PNA frequency (8.6 ± 6.4 %, p<0.05). These data suggest that ACH acting on muscarinic receptors in the NTS may play an important role in the control of sympathetic and respiratory activities with distinct responses depending on the NTS level.Supported by: FAPESP, CNPq.
Blockade of brain angiotensin II type 1 receptor attenuates angiotensin II‐induced left ventricular end‐diastolic pressure elevation and myocardial hypertrophy via sympathoinhibition
Authors: Shinohara Keisuke , Hirooka Yoshitaka , Kishi Takuya , Sunagawa Kenji 
Published: June 2021

BackgroundCentral sympathoexcitation is a cardinal manifestation of heart failure. The aims of the present study were to investigate whether central sympathoexcitation induced by slow presser dose of peripheral angiotensin II (Ang II) infusion deteriorates cardiac function in rats, and if so, to investigate whether blockade of Ang II type 1 receptor (AT1R) in the brain improve the changes of cardiac function via central sympathoinhibition.Methods and ResultsIn Sprague‐Dawley rats, the subcutaneous infusion of Ang II at 100 ng·kg−1·min−1 for 14 days increased gradually systolic blood pressure from baseline (+ 15±4 mmHg, n=11). Compared with vehicle infusion, Ang II‐infusion increased plasma Ang II (100±10 vs. 48±8 pg/ml, n=5~9, p<0.05), urinary norepinephrine excretion (1.25±0.03 vs. 0.92±0.05 μg/24 hrs, n=8~12, p<0.001), left ventricular end‐diastolic pressure (LVEDP) (5.0±0.4 vs. 2.7±0.3 mmHg, n=5~8, p<0.001) with myocardial hypertrophy. Chronic intracerebroventricular infusion of AT1R blocker, losartan, attenuated these Ang II‐induced changes. The percent fractional shortening evaluated by echocardiography did not differ between the groups.ConclusionCentral sympathoexcitation induced by increased plasma Ang II increases LVEDP with myocardial hypertrophy. Furthermore, the blockade of AT1R in the brain reduces the Ang II‐induced changes via sympathoinhibition.