Activation of the sympathetic nervous system increases sodium retention in resistant hypertension. Baroreflex activation therapy (BAT) is an interventional method to reduce sympathetic overactivity in patients with resistant hypertension. This study aimed to assess the effect of BAT on urinary sodium excretion.
From 2012 to 2015, consecutive patients with resistant hypertension and blood pressure (BP) above target despite polypharmacy strategies were consecutively included in this observational study. BAT was provided with the individual adaption of programmed parameters over the first months. 24-h urinary sodium excretion (UNa) was estimated at baseline and after 6 months using the Kawasaki formula in patients undergoing BAT. Additionally, the fractional sodium excretion, plasma renin activity, and aldosterone levels were assessed.
Forty-two patients completed the 6-month follow-up period. Office systolic and ambulatory 24-h systolic BP at baseline were 169 ± 27 mmHg and 148 ± 16 mmHg despite a median intake of 7(3–9) antihypertensive drugs. After 6 months of BAT, systolic office BP decreased to 150 ± 29 mmHg (p < 0.01), 24-h systolic BP to 142 ± 22 mmHg (p = 0.04) and 24-h UNa increased by 37% compared to baseline (128 ± 66 vs. 155 ± 83 mmol/day, p < 0.01). These findings were accompanied by a significant increase in fractional sodium excretion (0.74% [0.43–1.47] to 0.92% [0.61–1.92]; p = 0.02). However, in contrast to the significant BP reduction, eGFR, plasma sodium, renin activity and aldosterone levels did not change during BAT. The increase in sodium excretion was correlated with the change in eGFR (r = 0.371; p = 0.015).
The present study revealed a significant increase of estimated 24-h UNa which may contribute to the long-term BP-lowering effects of this interventional method.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Baroreflex activation therapy
Body mass index
Estimated glomerular filtration rate
Mineralocorticoid receptor antagonists
24-h urinary sodium excretion (UNa)
Renin–angiotensin aldosterone system
Wallbach M, Koziolek MJ (2018) Baroreceptors in the carotid and hypertension-systematic review and meta-analysis of the effects of baroreflex activation therapy on blood pressure. Nephrol Dial Transplant 33(9):1485–1493
Wallbach M, Lehnig LY, Helms HJ, Schroer C, Muller GA, Wachter R et al (2015) Long-term effects of baroreflex activation therapy on glucose metabolism. Acta Diabetol 52(5):829–835
Wallbach M, Lehnig LY, Schroer C, Helms HJ, Luders S, Patschan D et al (2015) Effects of baroreflex activation therapy on arterial stiffness and central hemodynamics in patients with resistant hypertension. J Hypertens 33(1):181–186
Wallbach M, Lehnig LY, Schroer C, Hasenfuss G, Muller GA, Wachter R et al (2014) Impact of baroreflex activation therapy on renal function—a pilot study. Am J Nephrol 40(4):371–380
Bisognano JD, Bakris G, Nadim MK, Sanchez L, Kroon AA, Schafer J et al (2011) Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: results from the double-blind, randomized, placebo-controlled rheos pivotal trial. J Am Coll Cardiol 58(7):765–773
de Leeuw PW, Bisognano JD, Bakris GL, Nadim MK, Haller H, Kroon AA (2017) Sustained reduction of blood pressure with baroreceptor activation therapy: results of the 6-year open follow-up. Hypertension 69(5):836–843
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
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):1020–1025
Hoogerwaard AF, Adiyaman A, de Jong MR, Smit JJJ, Delnoy P, Heeg JE et al (2018) Changes in arterial pressure hemodynamics in response to renal nerve stimulation both before and after renal denervation. Clin Res Cardiol 107(12):1131–1138
Fengler K, Rommel KP, Blazek S, Von Roeder M, Besler C, Lucke C et al (2018) Cardiac magnetic resonance assessment of central and peripheral vascular function in patients undergoing renal sympathetic denervation as predictor for blood pressure response. Clin Res Cardiol 107(10):945–955
Steinmetz M, Nelles D, Weisser-Thomas J, Schaefer C, Nickenig G, Werner N (2018) Flow-mediated dilation, nitroglycerin-mediated dilation and their ratio predict successful renal denervation in mild resistant hypertension. Clin Res Cardiol 107(7):611–615
Stoiber L, Mahfoud F, Zamani SM, Lapinskas T, Bohm M, Ewen S et al (2018) Renal sympathetic denervation restores aortic distensibility in patients with resistant hypertension: data from a multi-center trial. Clin Res Cardiol 107(8):642–652
Kulenthiran S, Ewen S, Bohm M, Mahfoud F (2017) Hypertension up to date: SPRINT to SPYRAL. Clin Res Cardiol 106(7):475–484
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):322–330
Blaustein MP, Zhang J, Chen L, Hamilton BP (2006) How does salt retention raise blood pressure? Am J Physiol Regul Integr Comp Physiol 290(3):R514–R523
Lohmeier TE, Iliescu R, Liu B, Henegar JR, Maric-Bilkan C, Irwin ED (2012) Systemic and renal-specific sympathoinhibition in obesity hypertension. Hypertension 59(2):331–338
Beevers G, Lip GY, O’Brien E (2001) ABC of hypertension: the pathophysiology of hypertension. Bmj 322(7291):912–916
Plakht Y, Gilutz H, Shiyovich A (2018) Sodium levels during hospitalization with acute myocardial infarction are markers of in-hospital mortality: soroka acute myocardial infarction II (SAMI-II) project. Clin Res Cardiol 107(10):956–964
Stolarz-Skrzypek K, Kuznetsova T, Thijs L, Tikhonoff V, Seidlerova J, Richart T et al (2011) Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. Jama 305(17):1777–1785
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr et al (2003) Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 42(6):1206–1252
Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M et al (2013) 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 34(28):2159–2219
Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M et al (2018) 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 39(33):3021–3104
Tordoir JH, Scheffers I, Schmidli J, Savolainen H, Liebeskind U, Hansky B et al (2007) An implantable carotid sinus baroreflex activating system: surgical technique and short-term outcome from a multi-center feasibility trial for the treatment of resistant hypertension. Eur J Vasc Endovasc Surg 33(4):414–421
Hoppe UC, Brandt MC, Wachter R, Beige J, Rump LC, Kroon AA et al (2012) Minimally invasive system for baroreflex activation therapy chronically lowers blood pressure with pacemaker-like safety profile: results from the Barostim neo trial. J Am Soc Hypertens 6(4):270–276
Wallbach M, Lehnig LY, Schroer C, Luders S, Bohning E, Muller GA et al (2016) Effects of baroreflex activation therapy on ambulatory blood pressure in patients with resistant hypertension. Hypertension 67(4):701–709
Mahfoud F, Ukena C, Schmieder RE, Cremers B, Rump LC, Vonend O et al (2013) Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension. Circulation 128(2):132–140
Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, Kusek JW, Manzi J, Van Lente F, Zhang YL, Coresh J, Levey AS (2012) CKD-EPI Investigators. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 367(1):20–29
Kawasaki T, Itoh K, Uezono K, Sasaki H (1993) A simple method for estimating 24 h urinary sodium and potassium excretion from second morning voiding urine specimen in adults. Clin Exp Pharmacol Physiol 20(1):7–14
Kawamura M, Kusano Y, Takahashi T, Owada M, Sugawara T (2006) Effectiveness of a spot urine method in evaluating daily salt intake in hypertensive patients taking oral antihypertensive drugs. Hypertens Res 29(6):397–402
Mente A, O’Donnell MJ, Dagenais G, Wielgosz A, Lear SA, McQueen MJ et al (2014) Validation and comparison of three formulae to estimate sodium and potassium excretion from a single morning fasting urine compared to 24-h measures in 11 countries. J Hypertens 32(5):1005–1014 (discussion 1015)
Bernstein AM, Willett WC (2010) Trends in 24-h urinary sodium excretion in the United States, 1957–2003: a systematic review. Am J Clin Nutr 92(5):1172–1180
Evans RG, Bie P (2016) Role of the kidney in the pathogenesis of hypertension: time for a neo-Guytonian paradigm or a paradigm shift? Am J Physiol Regul Integr Comp Physiol 310(3):R217–R229
Volz S, Svedlund S, Andersson B, Li-Ming G, Rundqvist B (2017) Coronary flow reserve in patients with resistant hypertension. Clin Res Cardiol 106(2):151–157
Hoogerwaard AF, de Jong MR, Adiyaman A, Smit JJJ, Delnoy P, Heeg JE et al (2019) Renal sympathetic denervation induces changes in heart rate variability and is associated with a lower sympathetic tone. Clin Res Cardiol 108(1):22–30
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–R641
Lohmeier TE, Hildebrandt DA, Dwyer TM, Barrett AM, Irwin ED, Rossing MA et al (2007) Renal denervation does not abolish sustained baroreflex-mediated reductions in arterial pressure. Hypertension 49(2):373–379
Hildebrandt DA, Irwin ED, Lohmeier TE (2016) Prolonged baroreflex activation abolishes salt-induced hypertension after reductions in kidney mass. Hypertension 68:1400–1406
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):672–678
Titze J, Dahlmann A, Lerchl K, Kopp C, Rakova N, Schroder A et al (2014) Spooky sodium balance. Kidney Int 85(4):759–767
Ott C, Kopp C, Dahlmann A, Schmid A, Linz P, Cavallaro A et al (2018) Impact of renal denervation on tissue Na(+) content in treatment-resistant hypertension. Clin Res Cardiol 107(1):42–48
Mancia G, Parati G (2004) Office compared with ambulatory blood pressure in assessing response to antihypertensive treatment: a meta-analysis. J Hypertens 22(3):435–445
Doumas M, Anyfanti P, Bakris G (2012) Should ambulatory blood pressure monitoring be mandatory for future studies in resistant hypertension: a perspective. J Hypertens 30(5):874–876
Peters TK, Kaczmarczyk G (1994) Plasma renin activity during hypotensive responses to electrical stimulation carotid sinus nerves in conscious dogs. Clin Exp Pharmacol Physiol 21(1):1–8
Lohmeier TE, Dwyer TM, Hildebrandt DA, Irwin ED, Rossing MA, Serdar DJ et al (2005) Influence of prolonged baroreflex activation on arterial pressure in angiotensin hypertension. Hypertension 46(5):1194–1200
Kirchheim HR, Finke R, Hackenthal E, Lowe W, Persson P (1985) Baroreflex sympathetic activation increases threshold pressure for the pressure-dependent renin release in conscious dogs. Pflugers Arch 405(2):127–135
Fyhrquist F, Kurppa K, Huuskonen M (1975) Plasma renin activity, blood pressure and sodium excretion during treatment with clonidine. Acta Med Scand 197(6):457–461
Jung O, Gechter JL, Wunder C, Paulke A, Bartel C, Geiger H et al (2013) Resistant hypertension? Assessment of adherence by toxicological urine analysis. J Hypertens 31(4):766–774
The authors thank Mrs. C. Biegler for assistance, Dr. D. Zenker, Dept. of thoracic-cardiac-vascular surgery, for BAT implantation, and the employees of CVRx for technical support.
Conflict of interest
MW and MK declare lecture fees and/or funding of CVRx. Research program, Faculty of Medicine, Georg-August-University Göttingen, to MW and a research grant from CVRx to MK and MW. ML, LYL, AKS, GM and SL declare that they have no conflict of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Lipphardt, M., Koziolek, M.J., Lehnig, L. et al. Effect of baroreflex activation therapy on renal sodium excretion in patients with resistant hypertension. Clin Res Cardiol 108, 1287–1296 (2019). https://doi.org/10.1007/s00392-019-01464-4
- Resistant hypertension
- Urinary sodium excretion
- Kawasaki formula
- Sympathetic nervous system
- Baroreflex activation therapy