Neuropeptide Y as an indicator of successful alterations in sympathetic nervous activity after renal sympathetic denervation

Dörr, Oliver; Ewen, Sebastian; Liebetrau, Christoph; Möllmann, Helge; Gaede, Luise; Linz, Dominik; Hohl, Mathias; Troidl, Christian; Bauer, Timm; Böhm, Michael; Hamm, Christian W.; Mahfoud, Felix; Nef, Holger

doi:10.1007/s00392-015-0874-8

Cited by 21 publications

(13 citation statements)

References 38 publications

(71 reference statements)

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“…The neurotransmitter NPY, a marker of sympathetic activity, has been demonstrated to be decreased after RDN. 28 Therefore, decreased NPY after RDN is consistent with the finding of reduced sympathetic nerve density and activity at the site of infarction and suggests that sympathetic nerve activity may also be reduced at noninfarcted sites as well. …”

Section: Presence Of Cardiac Sympathetic Nerves and Npysupporting

confidence: 80%

Effects of Renal Artery Denervation on Ventricular Arrhythmias in a Postinfarct Model

Jackson

Gizurarson

Azam

et al. 2017

Circ: Cardiovascular Interventions

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T he therapeutic potential of renal denervation (RDN) for cardiac arrhythmias was previously explored, yielding case reports and small case series that suggested RDN may be an effective adjunctive treatment in addition to medication and cardiac ablation for patients with ventricular tachycardia (VT) storm and atrial fibrillation.1-5 These promising results call for large-scale, well-controlled trials and detailed mechanistic evaluations. However, findings of the SYMPLICITY HTN-3 study (Renal Denervation in Patients With Uncontrolled Hypertension) have raised grave concerns over the benefits from RDN therapy for hypertension. 4 Hence, although RDN-based treatments are being developed for arrhythmias, it is important to reassess and confirm the antiarrhythmic potential of RDN in experiments designed to clearly demonstrate the impacts on cardiac electrophysiology. More importantly, the mechanistic basis of any antiarrhythmic effects should also be determined. See Editorial by Koruth and DukkipatiRDN has been shown to attenuate elevations in left ventricular end-diastolic pressure, suppress spontaneous premature beats, and reduce the incidence of ventricular fibrillation (VF) immediately post-acute coronary occlusion in pigs.6 RDN was also shown to reduce the incidence of ventricular arrhythmias (VAs) immediately after coronary occlusion in a similar acute canine model, in which RDN prolonged the ventricular effective refractory period (ERP) and the ventricular action potential duration, as well as decreased action potential duration dispersion. Although RDN is known to reduce renal sympathetic activity Background-The therapeutic potential of renal denervation (RDN) for arrhythmias has not been fully explored. Detailed mechanistic evaluation is in order. The objective of the present study was to determine the antiarrhythmic potential of RDN in a postinfarct animal model and to determine whether any benefits relate to RDN-induced reduction of sympathetic effectors on the myocardium. Methods and Results-Pigs implanted with single-chamber implantable cardioverter defibrillators to record ventricular arrhythmias (VAs) were subjected to percutaneous coronary occlusion to induce myocardial infarction. Two weeks later, a sham or real RDN treatment was performed bilaterally using the St Jude EnligHTN basket catheter. Parameters of ventricular remodeling and modulation of cardio-renal sympathetic axis were monitored for 3 weeks after myocardial infarction. Histological analysis of renal arteries yielded a mean neurofilament score of healthy nerves that was significantly lower in the real RDN group than in sham controls; damaged nerves were found only in the real RDN group. There was a 100% reduction in the rate of spontaneous VAs after real RDN and a 75% increase in the rate of spontaneous VAs after sham RDN (P=0.03). In the infarcted myocardium, presence of sympathetic nerves and tissue abundance of neuropeptide-Y, an indicator of sympathetic nerve activities, were significantly lower in the RDN group. Peak and mean sinus t...

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Section: Presence Of Cardiac Sympathetic Nerves and Npysupporting

confidence: 80%

Effects of Renal Artery Denervation on Ventricular Arrhythmias in a Postinfarct Model

Jackson

Gizurarson

Azam

et al. 2017

Circ: Cardiovascular Interventions

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“…As described, NPY is also a major component of the SNS; it is present in renal nerve fibers where it is costored with norepinephrine. Interestingly, several studies also describe direct, protective effects of denervation of the kidney [which is characterized by reduced circulating NPY (62)], independent of changes in blood pressure (63,64). In the context of glomerular disease, renal denervation protects against podocyte injury and albuminuria (64), and drugs to reduce sympathetic nerve activity have been successfully used to treat microalbuminuria in diabetic patients, despite having no effect on blood pressure (65).…”

Section: Discussionmentioning

confidence: 99%

A role for NPY-NPY2R signaling in albuminuric kidney disease

Lay

Barrington

Hurcombe

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Albuminuria is an independent risk factor for the progression to end-stage kidney failure, cardiovascular morbidity, and premature death. As such, discovering signaling pathways that modulate albuminuria is desirable. Here, we studied the transcriptomes of podocytes, key cells in the prevention of albuminuria, under diabetic conditions. We found thatNeuropeptide Y (NPY)was significantly down-regulated in insulin-resistant vs. insulin-sensitive mouse podocytes and in human glomeruli of patients with early and late-stage diabetic nephropathy, as well as other nondiabetic glomerular diseases. This contrasts with the increased plasma and urinary levels of NPY that are observed in such conditions. Studying NPY-knockout mice, we found that NPY deficiency in vivo surprisingly reduced the level of albuminuria and podocyte injury in models of both diabetic and nondiabetic kidney disease. In vitro, podocyte NPY signaling occurred via the NPY2 receptor (NPY2R), stimulating PI3K, MAPK, and NFAT activation. Additional unbiased proteomic analysis revealed that glomerular NPY-NPY2R signaling predicted nephrotoxicity, modulated RNA processing, and inhibited cell migration. Furthermore, pharmacologically inhibiting the NPY2R in vivo significantly reduced albuminuria in adriamycin-treated glomerulosclerotic mice. Our findings suggest a pathogenic role of excessive NPY-NPY2R signaling in the glomerulus and that inhibiting NPY-NPY2R signaling in albuminuric kidney disease has therapeutic potential.

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“…Up until today, no feedback is provided to the interventionist during the procedure and performing too few ablations per artery or targeting the wrong arterial segments could result in high variability of BP reduction or even in a complete adverse outcome. Several biomarkers have been investigated but did not provide relevant prognostic information for future BP response [13][14][15]. Renal nerve stimulation, which acutely raises BP, has yet not been investigated in larger, randomized, controlled trials [16].…”

Section: Discussionmentioning

confidence: 99%

A drug-induced hypotensive challenge to verify catheter-based radiofrequency renal denervation in an obese hypertensive swine model

et al. 2020

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Objective Sham-controlled trials provided proof-of-principle for the blood pressure-lowering effect of catheter-based renal denervation (RDN). However, indicators for the immediate assessment of treatment success are lacking. This study sought to investigate the impact of RDN on renal renin arteriovenous difference (renal renin AV-Δ) following a hypotensive challenge (HC). Methods Twelve hypertensive Ossabaw swine underwent either combined surgical and chemical (n = 3) or catheter-based RDN (n = 9). A telemetry monitor was implanted to acquire hemodynamic data continuously. Before and after RDN, a sodium nitroprusside-induced HC was performed. Renal renin AV-Δ was calculated as the difference of plasma renin concentrations drawn from the renal artery and vein. Results In total, complete renal renin AV data were obtained in eight animals at baseline and six animals at baseline and 3 months of follow-up. Baseline renal renin AV-Δ correlated inversely with change in 24-h minimum systolic (− 0.764, p = 0.02), diastolic (r = − 0.679, p = 0.04), and mean (r = − 0.663, p = 0.05) blood pressure. In the animals with complete renin secretion data at baseline and follow-up, the HC increased renal renin AV-Δ at baseline, while this effect was attenuated following RDN (0.55 ± 0.34 pg/ml versus − 0.10 ± 0.16 pg/ml, p = 0.003). Renin urinary excretion remained unchanged throughout the study (baseline 0.286 ± 0.187 pg/ml versus termination 0.305 ± 0.072 pg/ml, p = 0.789). Conclusion Renin secretion induced by HC was attenuated following RDN and may serve as an indicator for patient selection and guide successful RDN procedures.

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Neuropeptide Y as an indicator of successful alterations in sympathetic nervous activity after renal sympathetic denervation

Abstract: This study demonstrates an effect of RSD on serum NPY levels, a specific marker for sympathetic activity. The association between RSD-related changes in SBP and NPY levels provides further evidence of the effect of RSD on the sympathetic nervous system.

Cited by 21 publications

References 38 publications

Effects of Renal Artery Denervation on Ventricular Arrhythmias in a Postinfarct Model

Effects of Renal Artery Denervation on Ventricular Arrhythmias in a Postinfarct Model

A role for NPY-NPY2R signaling in albuminuric kidney disease

A drug-induced hypotensive challenge to verify catheter-based radiofrequency renal denervation in an obese hypertensive swine model

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