Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat

Li, Jian Dong; Cheng, Ai-Yuan; Huo, Yan-Li; Fan, Jie; Zhang, Yuping; Fang, Zhiqin; Sun, Haoran; Peng, Wei; Zhang, Jinshun; Wang, Haiping; Xue, Baojian

doi:10.1155/2016/3562634

Cited by 8 publications

(7 citation statements)

References 46 publications

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“…23 Also, the present findings are reinforced by a recent study showing that RD ameliorated heart failure through down-regulation of the brain RAAS and markers of inflammation in rats. 34 …”

Section: Discussionmentioning

confidence: 99%

Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring

et al. 2017

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P reeclampsia and gestational hypertension are common conditions affecting 5% to 7% of all pregnancies.1 Multiple casecontrol and cohort studies have demonstrated that offspring of hypertensive pregnancies have higher blood pressure (BP) in childhood and adolescence and are at increased risk of developing adult hypertension. [2][3][4][5][6][7] Studies investigating the mechanisms that contribute to the development of hypertension in the offspring of mothers with preeclampsia and gestational hypertension found that male adolescents had increased aldosterone levels, a trend for increased circulating renin activity 8 and increased sympathetic activity before and during isometric exercise. 9 These results suggest the renin-angiotensin-aldosterone system (RAAS) and sympathetic nerve activity (SNA) are involved in the development of higher BP in the offspring of mothers with high BP during pregnancy.Animal experiments have shown that uteroplacental insufficiency, protein restriction, chronic secondary hypertension, or glucocorticoid treatment during pregnancy leads to hypertension in the offspring. 10 Consistent with the RAAS and SNA playing a role in mediating the fetal programming of hypertension, several studies have demonstrated that both captopril, an angiotensin-converting enzyme-1 (ACE1) inhibitor, and losartan, an angiotensin II (ANG II) receptor blocker, administered in the drinking water reduced increased BP in the offspring of dams fed low-protein diet 11,12 and of spontaneously hypertensive rats, 13 whereas renal denervation (RD) abolished hypertension in the offspring from diabetic rats 14 or from pregnant rats with reduced uterine perfusion. 15,16 Moreover, Mizuno et al 17,18 demonstrated that the RAAS contributes to the enhancement of the renalAbstract-Numerous findings demonstrate that there is a strong association between maternal health during pregnancy and cardiovascular disease in adult offspring. The purpose of the present study was to test whether maternal gestational hypertension modulates brain renin-angiotensin-aldosterone system (RAAS) and proinflammatory cytokines that sensitizes angiotensin II-elicited hypertensive response in adult offspring. In addition, the role of renal nerves and the RAAS in the sensitization process was investigated. Reverse transcription polymerase chain reaction analyses of structures of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAAS components and proinflammatory cytokines in 10-week-old male offspring of hypertensive dams. Most of these increases were significantly inhibited by either renal denervation performed at 8 weeks of age or treatment with an angiotensinconverting enzyme inhibitor, captopril, in drinking water starting at weaning. When tested beginning at 10 weeks of age, a pressor dose of angiotensin II resulted in enhanced upregulation of mRNA expression of RAAS components and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented pressor response in mal...

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“…23 Also, the present findings are reinforced by a recent study showing that RD ameliorated heart failure through down-regulation of the brain RAAS and markers of inflammation in rats. 34 …”

Section: Discussionmentioning

confidence: 99%

Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring

et al. 2017

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“…Autonomic dysfunction as a broad term mainly refers to a condition in which tonic and reflex control of autonomic outflows is altered, favouring increased sympathetic nerve activity and depressed parasympathetic function (22). Autonomic dysfunction is associated with increased oxidative stress and elevated levels of proinflammatory cytokines (23,24). Several studies suggest that oxidative stress plays a role in the development of CAN in diabetic patients (25,26).…”

Section: Resultsmentioning

confidence: 99%

Cardiac Autonomic Dysfunction Is Associated With Risk of Diabetic Kidney Disease Progression in Type 2 Diabetes Mellitus

et al. 2022

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BackgroundEvidence on the relationship between heart rate variability (HRV) and albumin-to-creatinine ratio (ACR) combined with estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM) is rare. Thus, this study aimed to investigate the relationship between heart rate variability and the risk of diabetic kidney disease (DKD) progression in diabetes patients.MethodOverall, 747 T2DM patients who were admitted to the Second Affiliated Hospital of Nanchang University underwent 24-hour dynamic electrocardiograms for HRV analysis. Time-domain HRV measures included mean heart rate, standard deviation of the R-R interval (SDNN), SDNN index, root mean squared difference of successive RR intervals (RMSSD), and percent of adjacent RR intervals with a difference greater than 50 ms (PNN50). Frequency-domain measures included low frequency (LF), very low frequency (VLF), high frequency (HF) components and LF-to-HF ratio. The risk of DKD progression was determined by combining ACR and eGFR and stratified as low risk (Group A), moderately increased risk (Group B), high risk (Group C), and very high risk (Group D) based on the Kidney Disease: Improving Global Outcomes guidelines.ResultThere were significant differences in HRV parameters among the four risk groups (SDNN: 113 ms vs 109 ms vs 101 ms vs 81 ms, P<0.01; LF: 240.2 ms2 vs 241.1 ms2 vs 155.2 ms2 vs 141.9 ms2, P<0.01; LF-to-HF ratio: 1.70 vs 1.24 vs 1.12 vs 0.93, P<0.01; VLF: 723.7 ms2 vs 601.1 ms2 vs 446.4 ms2 vs 356.3 ms2, P<0.01). A very high risk of DKD progression was significantly associated with a lower SDNN (β=-19.5, 95% CI: -30.0 to -10.0, P<0.01), and moderately increased, high, and very high risks were associated with lower LF-to-HF ratio and VLF (P<0.05). Logistic regression analysis showed that group D had a higher risk of reduced SDNN, LF-to-HF ratio, and VLF compared with group A after adjusting for systolic blood pressure, glycated haemoglobin, haemoglobin, high-density lipoprotein cholesterol, and age (odds ratio (95% CI): 0.989 (0. 983–0.996), 0.674 (0.498–0.913), and 0.999 (0.999–1.000), respectively).ConclusionCardiac autonomic dysfunction is associated with a risk of DKD progression in adults with T2DM, and reduced heart rate variability increased such risk. Thus, HRV screening may be necessary in patients with T2DM, especially those with high proteinuria.

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“…Stimulation of β-adrenergic receptors induces cardiac myocyte apoptosis and fibrosis in the heart [ 6 ].Prolonged stimulation of the β-adrenergic neurohormonal axis has been shown to contribute to the progression of CHF and mortality in both animal models and humans. Amount of studies, whether clinical studies or animal studies showed that RDN could improve cardiac function in heart failure patients or animals by decreasing sympathetic nerve activity [ 7 – 11 ]. Our research group also showed that RDN improved cardiac function by decreasing cardiac oxidative stress [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Renal denervation improves cardiac function by attenuating myocardiocyte apoptosis in dogs after myocardial infarction

Wang

Song

et al. 2018

BMC Cardiovasc Disord

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BackgroundMyocardial apoptosis is important in the pathogenesis and progression of myocardial infarction-induced heart failure (MI-HF). Renal sympathetic denervation (RDN) has become a promising therapeutic strategy for the treatment of HF. Previous studies have shown that RDN could improve heart function Yao et al. (Exp Ther Med 14:4104-4110, 2017). However, whether and how RDN regulates myocardial apoptosis in MI-HF is unclear. This study sought to evaluate the effects of RDN on cardiac function and apoptosis-related gene expression in MI-HF dogs.MethodsEighteen healthy mongrel dogs were randomly divided into control group(n = 6), model group(n = 6) and treatment group(n = 6). MI-HF was established in model group and treatment group by anhydrous alcohol embolization, after heart failure dogs in the treatment group and model group proceeded bilateral renal artery ablation and bilateral renal arteriography, respectively. The cardiac function parameters were evaluated by echocardiographic; the serum NT-BNP level was detected by ELISA; the degree of myocardial fibrosis was observed through masson staining; the expression of MMP-2, MMP-9 in the cardiac were got by immunohistochemistry. TUNEL method was used to observe cardiomyocyte apoptotsis and calculate the apoptosis index (AI). Relative expression of Bcl-2 and Bax, Caspase3 and GRP78 were detected using RT-PCR and Western Blot. Renal artery H&E staining and serum creatinine were conducted to access the efficacy and safety of RDN.ResultsFour weeks after RDN, the LVEDD, LVESD and LVEDP decreased, and the LVEF and LVSP increased in the treatment group compared with those in the control group (all P < 0.05). Moreover, NT-BNP, an indicator of cardiac function was decreased. Additionally, MMP-2 and MMP-9 levels in the myocardium decreased significantly in the treatment group. Furthermore, the levels of Bax, and caspase 3 decreased, while the level of Bcl-2 increased. Thus, myocardial apoptosis was attenuated in RDN treated dogs. We also found that the level of GRP78 which is activated in response to endoplasmic reticulum (ER) stress, was decreased. However, serum creatinine levels were not significantly different between the RND-treated dogs and the control dogs.ConclusionCardiac function was improved by RDN treatment through regulating apoptosis and ER stress in cardiomyocytes in dogs after MI.

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Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat

Cited by 8 publications

References 46 publications

Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring

Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring

Cardiac Autonomic Dysfunction Is Associated With Risk of Diabetic Kidney Disease Progression in Type 2 Diabetes Mellitus

Renal denervation improves cardiac function by attenuating myocardiocyte apoptosis in dogs after myocardial infarction

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