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Published in: Clinical Research in Cardiology 1/2018

01-01-2018 | Original Paper

Impact of renal denervation on tissue Na+ content in treatment-resistant hypertension

Authors: Christian Ott, Christoph Kopp, Anke Dahlmann, Axel Schmid, Peter Linz, Alexander Cavallaro, Matthias Hammon, Tilmann Ditting, Roland Veelken, Michael Uder, Jens Titze, Roland E. Schmieder

Published in: Clinical Research in Cardiology | Issue 1/2018

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Abstract

Objectives

Renal denervation (RDN) has been introduced for reducing blood pressure (BP) in treatment-resistant hypertension (TRH). The precise mechanism how RDN exerts its BP-lowering effects are not yet fully understood. It is widely accepted that sodium (Na+) plays a crucial role in the pathogenesis of hypertensive disease. However, there is increasing evidence of osmotically inactive Na+ storage. We investigated the impact of RDN on Na+ homeostasis using estimation of salt intake, and measurement of tissue Na+ content.

Methods

In a study 41 patients with TRH (office BP ≥140/90 mmHg and diagnosis confirmed by 24-h ambulatory BP monitoring) underwent RDN. Tissue Na+ content was assessed non-invasively with 3.0 T magnetic resonance imaging before and 6 months after RDN. In addition, 24-h urinary Na+ excretion as an estimate of salt intake and spot urine Na+/K+ excretion were assessed. The study was registered at http://​www.​clinicaltrials.​gov (ID: NCT01687725).

Results

There was a significant fall in BP (office: −17 ± 20/−10 ± 12 mmHg; 24-h: −11 ± 13/−6 ± 9 mmHg, all p < 0.001) 6 months after RDN. In contrast, tissue Na+ content of the muscle (20.1 ± 3.9 vs. 20.7 ± 4.0 mmol/L, p = 0.229) and skin (24.4 ± 6.5 vs. 24.8 ± 6.6 mmol/L, p = 0.695) did not change after RDN. Moreover, there was also no change in salt intake after RDN, whereas Na+/K+ ratio only acutely increased.

Conclusions

Although RDN resulted in a substantial reduction of BP, tissue Na+ content of the muscle and skin was not mobilized and reduced. These data indicate that the BP reduction after RDN is unrelated to Na+ homeostasis.
Literature
1.
go back to reference Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365(9455):217–223CrossRefPubMed Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365(9455):217–223CrossRefPubMed
2.
go back to reference Lifton RP, Gharavi AG, Geller DS (2001) Molecular mechanisms of human hypertension. Cell 104(4):545–556CrossRefPubMed Lifton RP, Gharavi AG, Geller DS (2001) Molecular mechanisms of human hypertension. Cell 104(4):545–556CrossRefPubMed
3.
go back to reference Meneton P, Jeunemaitre X, de Wardener HE, MacGregor GA (2005) Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev 85(2):679–715CrossRefPubMed Meneton P, Jeunemaitre X, de Wardener HE, MacGregor GA (2005) Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev 85(2):679–715CrossRefPubMed
4.
go back to reference Smithwick RH, Thompson JE (1953) Splanchnicectomy for essential hypertension; results in 1,266 cases. J Am Med Assoc 152(16):1501–1504CrossRefPubMed Smithwick RH, Thompson JE (1953) Splanchnicectomy for essential hypertension; results in 1,266 cases. J Am Med Assoc 152(16):1501–1504CrossRefPubMed
5.
go back to reference Katholi RE (1985) Renal nerves and hypertension: an update. Fed Proc 44(13):2846–2850PubMed Katholi RE (1985) Renal nerves and hypertension: an update. Fed Proc 44(13):2846–2850PubMed
6.
go back to reference Pimenta E, Gaddam KK, Oparil S, Aban I, Husain S, Dell’Italia LJ et al (2009) Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Hypertension 54(3):475–481CrossRefPubMedPubMedCentral Pimenta E, Gaddam KK, Oparil S, Aban I, Husain S, Dell’Italia LJ et al (2009) Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Hypertension 54(3):475–481CrossRefPubMedPubMedCentral
7.
go back to reference Grassi G, Seravalle G, Brambilla G, Pini C, Alimento M, Facchetti R et al (2014) Marked sympathetic activation and baroreflex dysfunction in true resistant hypertension. Int J Cardiol 177(3):1020–1025CrossRefPubMed Grassi G, Seravalle G, Brambilla G, Pini C, Alimento M, Facchetti R et al (2014) Marked sympathetic activation and baroreflex dysfunction in true resistant hypertension. Int J Cardiol 177(3):1020–1025CrossRefPubMed
8.
go back to reference DiBona GF (2005) Physiology in perspective: the wisdom of the body Neural control of the kidney. Am J Physiol Regul Integr Comp Physiol 289(3):R633–R641CrossRefPubMed DiBona GF (2005) Physiology in perspective: the wisdom of the body Neural control of the kidney. Am J Physiol Regul Integr Comp Physiol 289(3):R633–R641CrossRefPubMed
9.
go back to reference Bobrie G, Frank M, Azizi M, Peyrard S, Boutouyrie P, Chatellier G et al (2012) Sequential nephron blockade versus sequential renin-angiotensin system blockade in resistant hypertension: a prospective, randomized, open blinded endpoint study. J Hypertens 30(8):1656–1664CrossRefPubMed Bobrie G, Frank M, Azizi M, Peyrard S, Boutouyrie P, Chatellier G et al (2012) Sequential nephron blockade versus sequential renin-angiotensin system blockade in resistant hypertension: a prospective, randomized, open blinded endpoint study. J Hypertens 30(8):1656–1664CrossRefPubMed
10.
go back to reference Poss J, Ewen S, Schmieder RE, Muhler S, Vonend O, Ott C et al (2015) Effects of renal sympathetic denervation on urinary sodium excretion in patients with resistant hypertension. Clin Res Cardiol 104(8):672–678CrossRefPubMed Poss J, Ewen S, Schmieder RE, Muhler S, Vonend O, Ott C et al (2015) Effects of renal sympathetic denervation on urinary sodium excretion in patients with resistant hypertension. Clin Res Cardiol 104(8):672–678CrossRefPubMed
11.
go back to reference Symplicity HTNI, Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE et al (2010) Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet 376(9756):1903–1909CrossRef Symplicity HTNI, Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE et al (2010) Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet 376(9756):1903–1909CrossRef
12.
go back to reference Brinkmann J, Heusser K, Schmidt BM, Menne J, Klein G, Bauersachs J et al (2012) Catheter-based renal nerve ablation and centrally generated sympathetic activity in difficult-to-control hypertensive patients: prospective case series. Hypertension 60(6):1485–1490CrossRefPubMed Brinkmann J, Heusser K, Schmidt BM, Menne J, Klein G, Bauersachs J et al (2012) Catheter-based renal nerve ablation and centrally generated sympathetic activity in difficult-to-control hypertensive patients: prospective case series. Hypertension 60(6):1485–1490CrossRefPubMed
13.
go back to reference Sharp AS, Davies JE, Lobo MD, Bent CL, Mark PB, Burchell AE et al (2016) Renal artery sympathetic denervation: observations from the UK experience. Clin Res Cardiol 105(6):544–552CrossRefPubMedPubMedCentral Sharp AS, Davies JE, Lobo MD, Bent CL, Mark PB, Burchell AE et al (2016) Renal artery sympathetic denervation: observations from the UK experience. Clin Res Cardiol 105(6):544–552CrossRefPubMedPubMedCentral
14.
go back to reference De Jager RL, Sanders MF, Bots ML, Lobo MD, Ewen S, Beeftink MM et al (2016) Renal denervation in hypertensive patients not on blood pressure lowering drugs. Clin Res Cardiol 105(9):755–762 (Epub 2016/04/24) CrossRefPubMedPubMedCentral De Jager RL, Sanders MF, Bots ML, Lobo MD, Ewen S, Beeftink MM et al (2016) Renal denervation in hypertensive patients not on blood pressure lowering drugs. Clin Res Cardiol 105(9):755–762 (Epub 2016/04/24) CrossRefPubMedPubMedCentral
15.
go back to reference Tsioufis C, Ziakas A, Dimitriadis K, Davlouros P, Marketou M, Kasiakogias A et al (2017) Blood pressure response to catheter-based renal sympathetic denervation in severe resistant hypertension: data from the Greek Renal Denervation Registry. Clin Res Cardiol 106(5):322–330CrossRefPubMed Tsioufis C, Ziakas A, Dimitriadis K, Davlouros P, Marketou M, Kasiakogias A et al (2017) Blood pressure response to catheter-based renal sympathetic denervation in severe resistant hypertension: data from the Greek Renal Denervation Registry. Clin Res Cardiol 106(5):322–330CrossRefPubMed
16.
go back to reference Ewen S, Meyer MR, Cremers B, Laufs U, Helfer AG, Linz D et al (2015) Blood pressure reductions following catheter-based renal denervation are not related to improvements in adherence to antihypertensive drugs measured by urine/plasma toxicological analysis. Clin Res Cardiol 104(12):1097–1105CrossRefPubMed Ewen S, Meyer MR, Cremers B, Laufs U, Helfer AG, Linz D et al (2015) Blood pressure reductions following catheter-based renal denervation are not related to improvements in adherence to antihypertensive drugs measured by urine/plasma toxicological analysis. Clin Res Cardiol 104(12):1097–1105CrossRefPubMed
17.
go back to reference Ewen S, Ukena C, Linz D, Kindermann I, Cremers B, Laufs U et al (2015) Reduced effect of percutaneous renal denervation on blood pressure in patients with isolated systolic hypertension. Hypertension 65(1):193–199CrossRefPubMed Ewen S, Ukena C, Linz D, Kindermann I, Cremers B, Laufs U et al (2015) Reduced effect of percutaneous renal denervation on blood pressure in patients with isolated systolic hypertension. Hypertension 65(1):193–199CrossRefPubMed
18.
go back to reference Dorr O, Liebetrau C, Mollmann H, Mahfoud F, Ewen S, Gaede L et al (2015) Beneficial effects of renal sympathetic denervation on cardiovascular inflammation and remodeling in essential hypertension. Clinical Res Cardiol 104(2):175–184CrossRef Dorr O, Liebetrau C, Mollmann H, Mahfoud F, Ewen S, Gaede L et al (2015) Beneficial effects of renal sympathetic denervation on cardiovascular inflammation and remodeling in essential hypertension. Clinical Res Cardiol 104(2):175–184CrossRef
19.
go back to reference Ott C, Schmid A, Toennes SW, Ditting T, Veelken R, Uder M et al (2015) Central pulse pressure predicts BP reduction after renal denervation in patients with treatment-resistant hypertension. EuroIntervention 11(1):110–116CrossRefPubMed Ott C, Schmid A, Toennes SW, Ditting T, Veelken R, Uder M et al (2015) Central pulse pressure predicts BP reduction after renal denervation in patients with treatment-resistant hypertension. EuroIntervention 11(1):110–116CrossRefPubMed
20.
go back to reference Guyton AC, Coleman TC, Cowley AWJ, Manning RD, Norman RAJ, Ferguson JD (1974) A systems analysis approach to understanding long-range arterial blood pressure control and hypertension. Circ Res 35:159–176CrossRef Guyton AC, Coleman TC, Cowley AWJ, Manning RD, Norman RAJ, Ferguson JD (1974) A systems analysis approach to understanding long-range arterial blood pressure control and hypertension. Circ Res 35:159–176CrossRef
21.
go back to reference Titze J, Krause H, Hecht H, Dietsch P, Rittweger J, Lang R et al (2002) Reduced osmotically inactive Na storage capacity and hypertension in the Dahl model. Am J Physiol Renal Physiol 283(1):F134–F141CrossRefPubMed Titze J, Krause H, Hecht H, Dietsch P, Rittweger J, Lang R et al (2002) Reduced osmotically inactive Na storage capacity and hypertension in the Dahl model. Am J Physiol Renal Physiol 283(1):F134–F141CrossRefPubMed
22.
go back to reference Titze J, Luft FC, Bauer K, Dietsch P, Lang R, Veelken R et al (2006) Extrarenal Na+ balance, volume, and blood pressure homeostasis in intact and ovariectomized deoxycorticosterone-acetate salt rats. Hypertension 47(6):1101–1107CrossRefPubMed Titze J, Luft FC, Bauer K, Dietsch P, Lang R, Veelken R et al (2006) Extrarenal Na+ balance, volume, and blood pressure homeostasis in intact and ovariectomized deoxycorticosterone-acetate salt rats. Hypertension 47(6):1101–1107CrossRefPubMed
23.
go back to reference Kopp C, Linz P, Wachsmuth L, Dahlmann A, Horbach T, Schofl C et al (2012) (23)Na magnetic resonance imaging of tissue sodium. Hypertension 59(1):167–172 (epub 2011/12/08) CrossRefPubMed Kopp C, Linz P, Wachsmuth L, Dahlmann A, Horbach T, Schofl C et al (2012) (23)Na magnetic resonance imaging of tissue sodium. Hypertension 59(1):167–172 (epub 2011/12/08) CrossRefPubMed
24.
go back to reference Kopp C, Linz P, Dahlmann A, Hammon M, Jantsch J, Muller DN et al (2013) 23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients. Hypertension 61(3):635–640 (epub 2013/01/23) CrossRefPubMed Kopp C, Linz P, Dahlmann A, Hammon M, Jantsch J, Muller DN et al (2013) 23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients. Hypertension 61(3):635–640 (epub 2013/01/23) CrossRefPubMed
25.
go back to reference Schmieder RE, Redon J, Grassi G, Kjeldsen SE, Mancia G, Narkiewicz K et al (2012) ESH position paper: renal denervation—an interventional therapy of resistant hypertension. J Hypertens 30(5):837–841CrossRefPubMed Schmieder RE, Redon J, Grassi G, Kjeldsen SE, Mancia G, Narkiewicz K et al (2012) ESH position paper: renal denervation—an interventional therapy of resistant hypertension. J Hypertens 30(5):837–841CrossRefPubMed
26.
go back to reference Schmieder RE, Redon J, Grassi G, Kjeldsen SE, Mancia G, Narkiewicz K et al (2013) Updated ESH position paper on interventional therapy of resistant hypertension. EuroIntervention. 9(suppl R):R58–R66CrossRefPubMed Schmieder RE, Redon J, Grassi G, Kjeldsen SE, Mancia G, Narkiewicz K et al (2013) Updated ESH position paper on interventional therapy of resistant hypertension. EuroIntervention. 9(suppl R):R58–R66CrossRefPubMed
27.
go back to reference Mahfoud F, Luscher TF, Andersson B, Baumgartner I, Cifkova R, Dimario C et al (2013) Expert consensus document from the European Society of Cardiology on catheter-based renal denervation. Eur Heart J 34(28):2149–2157CrossRefPubMed Mahfoud F, Luscher TF, Andersson B, Baumgartner I, Cifkova R, Dimario C et al (2013) Expert consensus document from the European Society of Cardiology on catheter-based renal denervation. Eur Heart J 34(28):2149–2157CrossRefPubMed
28.
go back to reference Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K et al (2009) Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 373(9671):1275–1281CrossRefPubMed Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K et al (2009) Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 373(9671):1275–1281CrossRefPubMed
29.
go back to reference O’Brien E, Atkins N, Stergiou G, Karpettas N, Parati G, Asmar R et al (2010) European Society of Hypertension International Protocol revision 2010 for the validation of blood pressure measuring devices in adults. Blood Press Monit 15(1):23–38CrossRefPubMed O’Brien E, Atkins N, Stergiou G, Karpettas N, Parati G, Asmar R et al (2010) European Society of Hypertension International Protocol revision 2010 for the validation of blood pressure measuring devices in adults. Blood Press Monit 15(1):23–38CrossRefPubMed
30.
go back to reference Intersalt Cooperative Research Group (1988) Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. BMJ 297(6644):319–328CrossRef Intersalt Cooperative Research Group (1988) Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. BMJ 297(6644):319–328CrossRef
31.
go back to reference Land MA, Webster J, Christoforou A, Praveen D, Jeffery P, Chalmers J et al (2014) Salt intake assessed by 24 h urinary sodium excretion in a random and opportunistic sample in Australia. BMJ Open 4(1):e003720CrossRefPubMedPubMedCentral Land MA, Webster J, Christoforou A, Praveen D, Jeffery P, Chalmers J et al (2014) Salt intake assessed by 24 h urinary sodium excretion in a random and opportunistic sample in Australia. BMJ Open 4(1):e003720CrossRefPubMedPubMedCentral
32.
go back to reference Langenfeld MR, Schobel H, Veelken R, Weihprecht H, Schmieder RE (1998) Impact of dietary sodium intake on left ventricular diastolic filling in early essential hypertension. Eur Heart J 19(6):951–958CrossRefPubMed Langenfeld MR, Schobel H, Veelken R, Weihprecht H, Schmieder RE (1998) Impact of dietary sodium intake on left ventricular diastolic filling in early essential hypertension. Eur Heart J 19(6):951–958CrossRefPubMed
33.
34.
go back to reference O’Donnell MJ, Yusuf S, Mente A, Gao P, Mann JF, Teo K et al (2011) Urinary sodium and potassium excretion and risk of cardiovascular events. JAMA 306(20):2229–2238PubMed O’Donnell MJ, Yusuf S, Mente A, Gao P, Mann JF, Teo K et al (2011) Urinary sodium and potassium excretion and risk of cardiovascular events. JAMA 306(20):2229–2238PubMed
35.
go back to reference Cao W, Li A, Wang L, Zhou Z, Su Z, Bin W et al (2015) A salt-induced reno-cerebral reflex activates renin-angiotensin systems and promotes CKD progression. J Am Soc Nephrol 26(7):1619–1633CrossRefPubMedPubMedCentral Cao W, Li A, Wang L, Zhou Z, Su Z, Bin W et al (2015) A salt-induced reno-cerebral reflex activates renin-angiotensin systems and promotes CKD progression. J Am Soc Nephrol 26(7):1619–1633CrossRefPubMedPubMedCentral
36.
go back to reference Rakova N, Juttner K, Dahlmann A, Schroder A, Linz P, Kopp C et al (2013) Long-term space flight simulation reveals infradian rhythmicity in human Na(+) balance. Cell Metab 17(1):125–131 (Epub 2013/01/15) CrossRefPubMed Rakova N, Juttner K, Dahlmann A, Schroder A, Linz P, Kopp C et al (2013) Long-term space flight simulation reveals infradian rhythmicity in human Na(+) balance. Cell Metab 17(1):125–131 (Epub 2013/01/15) CrossRefPubMed
37.
go back to reference Dahlmann A, Dorfelt K, Eicher F, Linz P, Kopp C, Mossinger I et al (2015) Magnetic resonance-determined sodium removal from tissue stores in hemodialysis patients. Kidney Int 87(2):434–441CrossRefPubMed Dahlmann A, Dorfelt K, Eicher F, Linz P, Kopp C, Mossinger I et al (2015) Magnetic resonance-determined sodium removal from tissue stores in hemodialysis patients. Kidney Int 87(2):434–441CrossRefPubMed
38.
go back to reference Mahfoud F, Schmieder RE, Azizi M, Pathak A, Sievert H, Tsioufis C, et al (2017) Proceedings from the 2nd European Clinical Consensus Conference for device-based therapies for hypertension: state of the art and considerations for the future. Eur Heart J. doi:10.1093/eurheartj/ehx215 Mahfoud F, Schmieder RE, Azizi M, Pathak A, Sievert H, Tsioufis C, et al (2017) Proceedings from the 2nd European Clinical Consensus Conference for device-based therapies for hypertension: state of the art and considerations for the future. Eur Heart J. doi:10.​1093/​eurheartj/​ehx215
39.
go back to reference Bhatt DL, Kandzari DE, O’Neill WW, D’Agostino R, Flack JM, Katzen BT et al (2014) A controlled trial of renal denervation for resistant hypertension. N Engl J Med 370(15):1393–1401CrossRefPubMed Bhatt DL, Kandzari DE, O’Neill WW, D’Agostino R, Flack JM, Katzen BT et al (2014) A controlled trial of renal denervation for resistant hypertension. N Engl J Med 370(15):1393–1401CrossRefPubMed
40.
41.
go back to reference Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M et al (2015) Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. Eur Heart J 36(4):219–227CrossRefPubMed Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M et al (2015) Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. Eur Heart J 36(4):219–227CrossRefPubMed
Metadata
Title
Impact of renal denervation on tissue Na+ content in treatment-resistant hypertension
Authors
Christian Ott
Christoph Kopp
Anke Dahlmann
Axel Schmid
Peter Linz
Alexander Cavallaro
Matthias Hammon
Tilmann Ditting
Roland Veelken
Michael Uder
Jens Titze
Roland E. Schmieder
Publication date
01-01-2018
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology / Issue 1/2018
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-017-1156-4

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