Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.; Patel, Kaushik P.

doi:10.1152/ajpheart.00999.2015

Cited by 24 publications

(19 citation statements)

References 49 publications

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“…It is possible that the damage induced by coronary artery ligation is fairly severe and prevalent for four weeks, which are difficult to reverse with reduction in sympathetic outflow mediated by A-RDN. Nevertheless, overall these data are consistent with our previous study showing that total renal denervation (ablation of both afferent and efferent renal nerves) improved cardiac function in rats with CHF 39 .…”

Section: Discussionsupporting

confidence: 93%

Specific Afferent Renal Denervation Prevents Reduction in Neuronal Nitric Oxide Synthase Within the Paraventricular Nucleus in Rats With Chronic Heart Failure

et al. 2018

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Renal denervation (RDN) has been shown to restore endogenous neuronal nitric oxide synthase (nNOS) in the paraventricular nucleus (PVN) and reduce sympathetic drive during chronic heart failure (CHF). The purpose of the present study was to assess the contribution of afferent renal nerves to the nNOS-mediated sympathetic outflow within the PVN in rats with CHF. CHF was induced in rats by ligation of the left coronary artery. Four weeks after surgery, selective afferent RDN (A-RDN) was performed by bilateral perivascular application of capsaicin on the renal arteries. Seven days after intervention, nNOS protein expression, nNOS immunostaining signaling, and diaphorase-positive stained cells were significantly decreased in the PVN of CHF rats, changes that were reversed by A-RDN. A-RDN reduced basal lumbar sympathetic nerve activity in rats with CHF (8.5%±0.5% versus 17.0%±1.2% of max). Microinjection of nNOS inhibitor L-NMMA (L-N-monomethyl arginine citrate) into the PVN produced a blunted increase in lumbar sympathetic nerve activity in rats with CHF. This response was significantly improved after A-RDN (Δ lumbar sympathetic nerve activity: 25.7%±2.4% versus 11.2%±0.9%). Resting afferent renal nerves activity was substantially increased in CHF compared with sham rats (56.3%±2.4% versus 33.0%±4.7%). These results suggest that intact afferent renal nerves contribute to the reduction of nNOS in the PVN. A-RDN restores nNOS and thus attenuates the sympathoexcitation. Also, resting afferent renal nerves activity is elevated in CHF rats, which may highlight a crucial neural mechanism arising from the kidney in the maintenance of enhanced sympathetic drive in CHF.

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Section: Discussionsupporting

confidence: 93%

Specific Afferent Renal Denervation Prevents Reduction in Neuronal Nitric Oxide Synthase Within the Paraventricular Nucleus in Rats With Chronic Heart Failure

et al. 2018

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“…The cardiac characteristics observed in this study are consistent with previous reports using this model of HF [41][42][43]. Additionally, substantial number of previous studies [44][45][46][47][48][49][50][51] demonstrated that natriuretic peptide levels in both the heart and the serum are significantly increased in rats with HF induced by coronary artery ligation used in the current study. Taken together, the ˃ 30% infarct size, increased LVEDP, LVEDD, LVESD, LVEDV and LVESV and decreased dP/dt, FS, EF, SV and CO all indicate that rats in HF group were experiencing cardiac dysfunction.…”

Section: Cardiac Characteristics Of the Hf Modelsupporting

confidence: 92%

GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation

Katsurada

Nandi

Zheng

et al. 2020

Cardiovasc Diabetol

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Background: Glucagon-like peptide-1 (GLP-1) induces diuresis and natriuresis. Previously we have shown that GLP-1 activates afferent renal nerve to increase efferent renal sympathetic nerve activity that negates the diuresis and natriuresis as a negative feedback mechanism in normal rats. However, renal effects of GLP-1 in heart failure (HF) has not been elucidated. The present study was designed to assess GLP-1-induced diuresis and natriuresis in rats with HF and its interactions with renal nerve activity. Methods: HF was induced in rats by coronary artery ligation. The direct recording of afferent renal nerve activity (ARNA) with intrapelvic injection of GLP-1 and total renal sympathetic nerve activity (RSNA) with intravenous infusion of GLP-1 were performed. GLP-1 receptor expression in renal pelvis, densely innervated by afferent renal nerve, was assessed by real-time PCR and western blot analysis. In separate group of rats after coronary artery ligation selective afferent renal denervation (A-RDN) was performed by periaxonal application of capsaicin, then intravenous infusion of GLP-1-induced diuresis and natriuresis were evaluated. Results: In HF, compared to sham-operated control; (1) response of increase in ARNA to intrapelvic injection of GLP-1 was enhanced (3.7 ± 0.4 vs. 2.0 ± 0.4 µV s), (2) GLP-1 receptor expression was increased in renal pelvis, (3) response of increase in RSNA to intravenous infusion of GLP-1 was enhanced (132 ± 30% vs. 70 ± 16% of the baseline level), and (4) diuretic and natriuretic responses to intravenous infusion of GLP-1 were blunted (urine flow 53.4 ± 4.3 vs. 78.6 ± 4.4 µl/min/gkw, sodium excretion 7.4 ± 0.8 vs. 10.9 ± 1.0 µEq/min/gkw). A-RDN induced significant increases in diuretic and natriuretic responses to GLP-1 in HF (urine flow 96.0 ± 1.9 vs. 53.4 ± 4.3 µl/min/gkw, sodium excretion 13.6 ± 1.4 vs. 7.4 ± 0.8 µEq/min/gkw). Conclusions: The excessive activation of neural circuitry involving afferent and efferent renal nerves suppresses diuretic and natriuretic responses to GLP-1 in HF. These pathophysiological responses to GLP-1 might be involved in the interaction between incretin-based medicines and established HF condition. RDN restores diuretic and natriuretic effects of GLP-1 and thus has potential beneficial therapeutic implication for diabetic HF patients.

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“…During HF, downregulation and desensitization of β‐adrenoceptors may be associated with the impairment of the PI3K/AKT/eNOS signaling pathway 33. On the other hand, it has been demonstrated that RDN blunted loss of β 1 ‐adrenoceptor and β 2 ‐adrenoceptor protein expression in HF models 34. Therefore, the beneficial effect of RDN on cardiac remodeling may be related to prevention of the downregulation of the PI3K/AKT/eNOS signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Impact of Renal Denervation on Atrial Arrhythmogenic Substrate in Ischemic Model of Heart Failure

Yamada

Fong

Hsiao

et al. 2018

JAHA

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BackgroundMyocardial infarction increases the risk of heart failure (HF) and atrial fibrillation. Renal denervation (RDN) might suppress the development of atrial remodeling. This study aimed to elucidate the molecular mechanism of RDN in the suppression of atrial fibrillation in a HF model after myocardial infarction.Methods and Results HF rabbits were created 4 weeks after coronary ligation. Rabbits were classified into 3 groups: normal control (n=10), HF (n=10), and HF‐RDN (n=6). Surgical and chemical RDN were approached through midabdominal incisions in HF‐RDN. Left anterior descending coronary artery in HF and HF‐RDN was ligated to create myocardial infarction. After electrophysiological study, the rabbits were euthanized and the left atrial appendage was harvested for real‐time polymerase chain reaction analysis and Trichrome stain. Left atrial dimension and left ventricular mass were smaller in HF‐RDN by echocardiography compared with HF. Attenuated atrial fibrosis and tyrosine hydroxylase levels were observed in HF‐RDN compared with HF. The mRNA expressions of Cav1.2, Nav1.5, Kir2.1, KvLQT1, phosphoinositide 3‐kinase, AKT, and endothelial nitric oxide synthase in HF‐RDN were significantly higher compared with HF. The effective refractory period and action potential duration of HF‐RDN were significantly shorter compared with HF. Decreased atrial fibrillation inducibility was noted in HF‐RDN compared with HF (50% versus 100%, P<0.05).Conclusions RDN reversed atrial electrical and structural remodeling, and suppressed the atrial fibrillation inducibility in an ischemic HF model. The beneficial effect of RDN may be related to prevention of the downregulation of the phosphoinositide 3‐kinase/AKT/endothelial nitric oxide synthase signaling pathway.

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Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

Cited by 24 publications

References 49 publications

Specific Afferent Renal Denervation Prevents Reduction in Neuronal Nitric Oxide Synthase Within the Paraventricular Nucleus in Rats With Chronic Heart Failure

Specific Afferent Renal Denervation Prevents Reduction in Neuronal Nitric Oxide Synthase Within the Paraventricular Nucleus in Rats With Chronic Heart Failure

GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation

Impact of Renal Denervation on Atrial Arrhythmogenic Substrate in Ischemic Model of Heart Failure

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