{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T05:32:53Z","timestamp":1778909573455,"version":"3.51.4"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1054619"],"award-info":[{"award-number":["1054619"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1078164"],"award-info":[{"award-number":["1078164"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1080404"],"award-info":[{"award-number":["1080404"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1041844"],"award-info":[{"award-number":["1041844"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Renal sympathetic nerves contribute to renal excretory function during volume expansion. We hypothesized that intact renal innervation is required for excretion of a fluid\/electrolyte load in hypertensive chronic kidney disease (CKD) and normotensive healthy settings. Blood pressure, kidney hemodynamic and excretory response to 180\u00a0min of isotonic saline loading (0.13\u00a0ml\/kg\/min) were examined in female normotensive (control) and hypertensive CKD sheep at 2 and 11\u00a0months after sham (control-intact, CKD-intact) or radiofrequency catheter-based RDN (control-RDN, CKD-RDN) procedure. Basal blood pressure was\u2009~\u20097 to 9\u00a0mmHg lower at 2, and 11\u00a0months in CKD-RDN compared with CKD-intact sheep. Saline loading did not alter glomerular filtration rate in any group. At 2\u00a0months, in response to saline loading, total urine and sodium excretion were\u2009~\u200940 to 50% less, in control-RDN and CKD-RDN than intact groups. At 11\u00a0months, the natriuretic and diuretic response to saline loading were similar between control-intact, control-RDN and CKD-intact groups but sodium excretion was\u2009~\u200942% less in CKD-RDN compared with CKD-intact at this time-point. These findings indicate that chronic withdrawal of basal renal sympathetic activity impairs fluid\/electrolyte excretion during volume expansion. Clinically, a reduced ability to excrete a saline load following RDN may contribute to disturbances in body fluid balance in hypertensive CKD.<\/jats:p>","DOI":"10.1038\/s41598-021-94221-5","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T10:26:57Z","timestamp":1626776817000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Blunted natriuretic response to saline loading in sheep with hypertensive kidney disease following radiofrequency catheter-based renal denervation"],"prefix":"10.1038","volume":"11","author":[{"given":"Reetu R.","family":"Singh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoe","family":"McArdle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harshil","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsea C.","family":"Booth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clive N.","family":"May","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey A.","family":"Head","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen M.","family":"Moritz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus P.","family":"Schlaich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate M.","family":"Denton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"issue":"1","key":"94221_CR1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1152\/physrev.1997.77.1.75","volume":"77","author":"G Dibona","year":"1997","unstructured":"Dibona, G. & Kopp, U. Neural control of renal function. Physiol. Rev. 77(1), 75\u2013197 (1997).","journal-title":"Physiol. Rev."},{"key":"94221_CR2","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3389\/fmed.2018.00082","volume":"5","author":"Y Sata","year":"2018","unstructured":"Sata, Y. et al. Role of the sympathetic nervous system and its modulation in renal hypertension. Front. Med. (Lausanne) 5, 82. https:\/\/doi.org\/10.3389\/fmed.2018.00082 (2018) ((eCollection 2018)).","journal-title":"Front. Med. (Lausanne)"},{"issue":"4","key":"94221_CR3","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1177\/1074248415624156","volume":"21","author":"Y Sata","year":"2016","unstructured":"Sata, Y. & Schlaich, M. P. The potential role of catheter-based renal sympathetic denervation in chronic and end-stage kidney disease. J. Cardiovasc. Pharmacol. Ther. 21(4), 344\u2013352. https:\/\/doi.org\/10.1177\/1074248415624156 (2016) ((Epub 2016 Jan 6)).","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"94221_CR4","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1161\/HYPERTENSIONAHA.118.10265","volume":"72","author":"R Singh","year":"2018","unstructured":"Singh, R. & Denton, K. Renal Denervation: A treatment for hypertension and chronic kidney disease. Hypertension 72, 528\u2013536 (2018).","journal-title":"Hypertension"},{"key":"94221_CR5","first-page":"18","volume":"591","author":"GF DiBona","year":"1990","unstructured":"DiBona, G. F. Role of renal nerves in volume homeostasis. Acta Physiol. Scand. Suppl. 591, 18\u201327 (1990).","journal-title":"Acta Physiol. Scand. Suppl."},{"issue":"3","key":"94221_CR6","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1113\/jphysiol.1969.sp008932","volume":"204","author":"JP Bonjour","year":"1969","unstructured":"Bonjour, J. P., Churchill, P. C. & Malvin, R. L. Change of tubular reabsorption of sodium and water after renal denervation in the dog. J. Physiol. 204(3), 571\u2013582. https:\/\/doi.org\/10.1113\/jphysiol.1969.sp008932 (1969).","journal-title":"J. Physiol."},{"issue":"1","key":"94221_CR7","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1113\/jphysiol.1968.sp008494","volume":"196","author":"WD Blake","year":"1968","unstructured":"Blake, W. D. & Jurf, A. N. Renal sodium reabsorption after acute renal denervation in the rabbit. J. Physiol. 196(1), 65\u201373. https:\/\/doi.org\/10.1113\/jphysiol.1968.sp008494 (1968).","journal-title":"J. Physiol."},{"issue":"8","key":"94221_CR8","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1007\/s00392-015-0832-5","volume":"104","author":"J P\u00f6ss","year":"2015","unstructured":"P\u00f6ss, J. et al. Effects of renal sympathetic denervation on urinary sodium excretion in patients with resistant hypertension. Clin. Res. Cardiol. 104(8), 672\u2013678 (2015).","journal-title":"Clin. Res. Cardiol."},{"issue":"12","key":"94221_CR9","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1172\/JCI103393","volume":"35","author":"NS Bricker","year":"1956","unstructured":"Bricker, N. S. et al. Studies on the functional capacity of a denervated homotransplanted kidney in an identical twin with parallel observations in the donor. J. Clin. Invest. 35(12), 1364\u20131380 (1956).","journal-title":"J. Clin. Invest."},{"key":"94221_CR10","first-page":"1","volume":"56","author":"H Ginn","year":"1960","unstructured":"Ginn, H. et al. Human renal transplantation: An investigation of the functional status of the denervated kidney after successful homotransplantation in identical twins. J. Lab. Clin. Med. 56, 1\u201313 (1960).","journal-title":"J. Lab. Clin. Med."},{"issue":"4","key":"94221_CR11","first-page":"F262","volume":"237","author":"J Sadowski","year":"1979","unstructured":"Sadowski, J., Kurkus, J. & Gellert, R. Denervated and intact kidney responses to saline load in awake and anesthetized dogs. Am. J. Physiol. 237(4), F262\u2013F267 (1979).","journal-title":"Am. J. Physiol."},{"issue":"3 Pt 2","key":"94221_CR12","first-page":"R388","volume":"255","author":"TV Peterson","year":"1988","unstructured":"Peterson, T. V., Benjamin, B. A. & Hurst, N. L. Renal nerves and renal responses to volume expansion in conscious monkeys. Am. J. Physiol. 255(3 Pt 2), R388\u2013R394 (1988).","journal-title":"Am. J. Physiol."},{"issue":"3","key":"94221_CR13","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/S0895-7061(96)00413-X","volume":"10","author":"S Kassab","year":"1997","unstructured":"Kassab, S. et al. Role of renal nerves in mediating the blunted natriuretic response to acute saline load in obese dogs. Am. J. Hypertens. 10(3), 315\u2013322 (1997).","journal-title":"Am. J. Hypertens."},{"issue":"6 Pt 2","key":"94221_CR14","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1161\/01.HYP.23.6.997","volume":"23","author":"S Kassab","year":"1994","unstructured":"Kassab, S. et al. Blunted natriuretic response to a high-sodium meal in obese dogs. Role of renal nerves. Hypertension 23(6 Pt 2), 997\u20131001 (1994).","journal-title":"Hypertension"},{"issue":"2","key":"94221_CR15","doi-asserted-by":"publisher","first-page":"R319","DOI":"10.1152\/ajpregu.00228.2018","volume":"317","author":"Z McArdle","year":"2019","unstructured":"McArdle, Z. et al. Blunted diuretic and natriuretic responses to acute sodium loading early after catheter-based renal denervation in normotensive sheep. Am. J. Physiol. Regul. Integr. Comp. Physiol. 317(2), R319\u2013R327. https:\/\/doi.org\/10.1152\/ajpregu.00228.2018 (2019) ((Epub 2019 Jun 5)).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"94221_CR16","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1016\/S0140-6736(18)31082-1","volume":"391","author":"M Azizi","year":"2018","unstructured":"Azizi, M. et al. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): A multicentre, international, single-blind, randomised, sham-controlled trial. Lancet 391, 2335\u20132345 (2018).","journal-title":"Lancet"},{"key":"94221_CR17","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.1016\/S0140-6736(18)30951-6","volume":"391","author":"DE Kandzari","year":"2018","unstructured":"Kandzari, D. E. et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet 391, 2346\u20132355 (2018).","journal-title":"Lancet"},{"issue":"9","key":"94221_CR18","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1056\/NEJMc0904179","volume":"361","author":"MP Schlaich","year":"2009","unstructured":"Schlaich, M. P. et al. Renal sympathetic-nerve ablation for uncontrolled hypertension. N. Engl. J. Med. 361(9), 932\u2013934 (2009).","journal-title":"N. Engl. J. Med."},{"issue":"10108","key":"94221_CR19","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1016\/S0140-6736(17)32281-X","volume":"390","author":"RR Townsend","year":"2017","unstructured":"Townsend, R. R. et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): A randomised, sham-controlled, proof-of-concept trial. Lancet 390(10108), 2160\u20132170 (2017).","journal-title":"Lancet"},{"key":"94221_CR20","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.ijcard.2017.01.047","volume":"232","author":"D Hering","year":"2017","unstructured":"Hering, D. et al. Effect of renal denervation on kidney function in patients with chronic kidney disease. Int. J. Cardiol. 232, 93\u201397 (2017).","journal-title":"Int. J. Cardiol."},{"key":"94221_CR21","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.ijcard.2016.08.262","volume":"223","author":"MG Kiuchi","year":"2016","unstructured":"Kiuchi, M. G. & Chen, S. Improvement of renal function after renal sympathetic denervation in CKD patients with controlled vs. uncontrolled hypertension. Int. J. Cardiol. 223, 494\u2013496. https:\/\/doi.org\/10.1016\/j.ijcard.2016.08.262 (2016) ((Epub 2016 Aug 16)).","journal-title":"Int. J. Cardiol."},{"issue":"2","key":"94221_CR22","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1161\/HYPERTENSIONAHA.112.193870","volume":"60","author":"F Mahfoud","year":"2012","unstructured":"Mahfoud, F. et al. Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension. Hypertension 60(2), 419\u2013424. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.112.193870 (2012) ((Epub 2012 Jun 25)).","journal-title":"Hypertension"},{"issue":"2","key":"94221_CR23","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.ijcard.2014.03.017","volume":"173","author":"C Ott","year":"2014","unstructured":"Ott, C. et al. Improvement of albuminuria after renal denervation. Int. J. Cardiol. 173(2), 311\u2013315. https:\/\/doi.org\/10.1016\/j.ijcard.2014.03.017 (2014) ((Epub 2014 Mar 15)).","journal-title":"Int. J. Cardiol."},{"issue":"6","key":"94221_CR24","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1097\/HJH.0000000000000556","volume":"33","author":"C Ott","year":"2015","unstructured":"Ott, C. et al. Renal denervation preserves renal function in patients with chronic kidney disease and resistant hypertension. J. Hypertens. 33(6), 1261\u20131266 (2015).","journal-title":"J. Hypertens."},{"issue":"2","key":"94221_CR25","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1161\/HYPERTENSIONAHA.114.04176","volume":"65","author":"LC Booth","year":"2015","unstructured":"Booth, L. C. et al. Reinnervation of renal afferent and efferent nerves at 5.5 and 11 months after catheter-based radiofrequency renal denervation in sheep. Hypertension 65(2), 393\u2013400 (2015).","journal-title":"Hypertension"},{"issue":"2","key":"94221_CR26","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1097\/HJH.0b013e32831bc778","volume":"27","author":"R Singh","year":"2009","unstructured":"Singh, R. et al. Development of cardiovascular disease due to renal insufficiency in male sheep following fetal unilateral nephrectomy. J. Hypertens. 27(2), 386\u2013396 (2009).","journal-title":"J. Hypertens."},{"issue":"8","key":"94221_CR27","doi-asserted-by":"publisher","first-page":"e42400","DOI":"10.1371\/journal.pone.0042400","volume":"7","author":"RR Singh","year":"2012","unstructured":"Singh, R. R. et al. Increased cardiovascular and renal risk is associated with low nephron endowment in aged females: An ovine model of fetal unilateral nephrectomy. PLoS\u00a0One 7(8), e42400. https:\/\/doi.org\/10.1371\/journal.pone.0042400 (2012) ((Epub 2012 Aug 3)).","journal-title":"PLoS\u00a0One"},{"issue":"10","key":"94221_CR28","first-page":"12250","volume":"21","author":"RR Singh","year":"2019","unstructured":"Singh, R. R. et al. Sustained decrease in blood pressure and reduced anatomical and functional reinnervation of renal nerves in hypertensive sheep 30 months after catheter-based renal denervation. Hypertension 21(10), 12250 (2019).","journal-title":"Hypertension"},{"issue":"8","key":"94221_CR29","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.jacc.2016.12.014","volume":"69","author":"RR Singh","year":"2017","unstructured":"Singh, R. R. et al. Catheter-based renal denervation exacerbates blood pressure fall during hemorrhage. J. Am. Coll. Cardiol. 69(8), 951\u2013964 (2017).","journal-title":"J. Am. Coll. Cardiol."},{"issue":"10","key":"94221_CR30","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1093\/ajh\/hpu048","volume":"27","author":"JR Henegar","year":"2014","unstructured":"Henegar, J. R. et al. Catheter-based radiofrequency renal denervation lowers blood pressure in obese hypertensive dogs. Am. J. Hypertens. 27(10), 1285\u20131292 (2014).","journal-title":"Am. J. Hypertens."},{"issue":"9917","key":"94221_CR31","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/S0140-6736(13)62192-3","volume":"383","author":"H Krum","year":"2014","unstructured":"Krum, H. et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: Final 3-year report of the Symplicity HTN-1 study. Lancet 383(9917), 622\u2013629 (2014).","journal-title":"Lancet"},{"issue":"8","key":"94221_CR32","doi-asserted-by":"publisher","first-page":"814","DOI":"10.4330\/wjc.v6.i8.814","volume":"6","author":"A Kannan","year":"2014","unstructured":"Kannan, A. et al. Renal sympathetic nervous system and the effects of denervation on renal arteries. World J. Cardiol. 6(8), 814\u2013823 (2014).","journal-title":"World J. Cardiol."},{"issue":"1","key":"94221_CR33","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3181\/00379727-182-42306","volume":"182","author":"GF DiBona","year":"1986","unstructured":"DiBona, G. F. & Sawin, L. L. Exaggerated natriuresis in experimental hypertension. Proc. Soc. Exp. Biol. Med. 182(1), 43\u201351 (1986).","journal-title":"Proc. Soc. Exp. Biol. Med."},{"issue":"2","key":"94221_CR34","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/j.1748-1716.1981.tb06800.x","volume":"112","author":"SE Ricksten","year":"1981","unstructured":"Ricksten, S. E. et al. Renal nerve activity and exaggerated natriuresis in conscious spontaneously hypertensive rats. Acta Physiol. Scand. 112(2), 161\u2013167 (1981).","journal-title":"Acta Physiol. Scand."},{"issue":"5","key":"94221_CR35","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1097\/00004872-198510000-00013","volume":"3","author":"NH Holstein-Rathlou","year":"1985","unstructured":"Holstein-Rathlou, N. H., Svendsen, U. G. & Leyssac, P. P. Effects of acute volume loading on kidney function in patients with essential hypertension, as estimated by the lithium clearance method. J. Hypertens. 3(5), 511\u2013516 (1985).","journal-title":"J. Hypertens."},{"issue":"6 Pt 2","key":"94221_CR36","first-page":"F1085","volume":"255","author":"A Mimran","year":"1988","unstructured":"Mimran, A. et al. Response of atrial natriuretic peptide to acute saline loading in essential hypertension. Am. J. Physiol. 255(6 Pt 2), F1085\u2013F1090 (1988).","journal-title":"Am. J. Physiol."},{"issue":"2","key":"94221_CR37","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1172\/JCI106509","volume":"50","author":"FD Gutmann","year":"1971","unstructured":"Gutmann, F. D. & Rieselbach, R. E. Disproportionate inhibition of sodium reabsorption in the unilaterally diseased kidney of dog and man after an acute saline load. J. Clin. Invest. 50(2), 422\u2013431 (1971).","journal-title":"J. Clin. Invest."},{"issue":"2","key":"94221_CR38","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1172\/JCI107195","volume":"52","author":"SF Wen","year":"1973","unstructured":"Wen, S. F. et al. Micropuncture studies of sodium transport in the remnant kidney of the dog. The effect of graded volume expansion. J. Clin. Invest. 52(2), 386\u2013387 (1973).","journal-title":"J. Clin. Invest."},{"issue":"2","key":"94221_CR39","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1111\/j.1748-1716.1984.tb00133.x","volume":"120","author":"S Lundin","year":"1984","unstructured":"Lundin, S., Ricksten, S. E. & Thor\u00e9n, P. Renal sympathetic activity in spontaneously hypertensive rats and normotensive controls, as studied by three different methods. Acta Physiol. Scand. 120(2), 265\u2013272 (1984).","journal-title":"Acta Physiol. Scand."},{"issue":"18","key":"94221_CR40","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1093\/eurheartj\/ehu091","volume":"35","author":"M Esler","year":"2014","unstructured":"Esler, M. Renal denervation for hypertension: Observations and predictions of a founder. Eur. Heart J. 35(18), 1178\u20131185 (2014).","journal-title":"Eur. Heart J."},{"issue":"3","key":"94221_CR41","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1097\/01.ASN.0000113320.57127.B9","volume":"15","author":"HA Koomans","year":"2004","unstructured":"Koomans, H. A., Blankestijn, P. J. & Joles, J. A. Sympathetic hyperactivity in chronic renal failure: A wake-up call. J. Am. Soc. Nephrol. 15(3), 524\u2013537 (2004).","journal-title":"J. Am. Soc. Nephrol."},{"issue":"17","key":"94221_CR42","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1056\/NEJM199904293401704","volume":"340","author":"G Ligtenberg","year":"1999","unstructured":"Ligtenberg, G. et al. Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure. N. Engl. J. Med. 340(17), 1321\u20131328 (1999).","journal-title":"N. Engl. J. Med."},{"key":"94221_CR43","first-page":"5","volume":"21","author":"MR Noh","year":"2020","unstructured":"Noh, M. R. et al. Renal sympathetic nerve-derived signaling in acute and chronic kidney diseases. Int. J. Mol. Sci. 21, 5 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"94221_CR44","doi-asserted-by":"publisher","first-page":"218","DOI":"10.3389\/fphys.2015.00218","volume":"6","author":"IM Salman","year":"2015","unstructured":"Salman, I. M. et al. Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease. Front. Physiol. 6, 218 (2015).","journal-title":"Front. Physiol."},{"issue":"3","key":"94221_CR45","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1161\/CIRCULATIONAHA.114.013930","volume":"131","author":"YR Lankadeva","year":"2015","unstructured":"Lankadeva, Y. R. et al. Renal dysfunction is associated with a reduced contribution of nitric oxide and enhanced vasoconstriction after a congenital renal mass reduction in sheep. Circulation 131(3), 280\u2013288 (2015).","journal-title":"Circulation"},{"issue":"10","key":"94221_CR46","doi-asserted-by":"publisher","first-page":"e47528","DOI":"10.1371\/journal.pone.0047528","volume":"7","author":"YR Lankadeva","year":"2012","unstructured":"Lankadeva, Y. R. et al. Blunted sodium excretion in response to a saline load in 5 year old female sheep following fetal uninephrectomy. PLoS\u00a0One 7(10), e47528 (2012).","journal-title":"PLoS\u00a0One"},{"issue":"1 Pt 2","key":"94221_CR47","first-page":"R278","volume":"268","author":"MD Esler","year":"1995","unstructured":"Esler, M. D. et al. Aging effects on human sympathetic neuronal function. Am. J. Physiol. 268(1 Pt 2), R278\u2013R285 (1995).","journal-title":"Am. J. Physiol."},{"issue":"1","key":"94221_CR48","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1161\/01.HYP.11.1.3","volume":"11","author":"M Esler","year":"1988","unstructured":"Esler, M. et al. Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension 11(1), 3\u201320 (1988).","journal-title":"Hypertension"},{"issue":"5","key":"94221_CR49","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1161\/01.HYP.7.5.714","volume":"7","author":"HA Koomans","year":"1985","unstructured":"Koomans, H. A. et al. Sodium balance in renal failure. A comparison of patients with normal subjects under extremes of sodium intake. Hypertension 7(5), 714\u2013721 (1985).","journal-title":"Hypertension"},{"issue":"1 Pt 2","key":"94221_CR50","first-page":"F15","volume":"248","author":"GF DiBona","year":"1985","unstructured":"DiBona, G. F. & Sawin, L. L. Renal nerve activity in conscious rats during volume expansion and depletion. Am. J. Physiol. 248(1 Pt 2), F15-23 (1985).","journal-title":"Am. J. Physiol."},{"issue":"6 Pt 2","key":"94221_CR51","first-page":"F890","volume":"260","author":"MS Mozaffari","year":"1991","unstructured":"Mozaffari, M. S. et al. High-NaCl diets increase natriuretic and diuretic responses in salt-resistant but not salt-sensitive SHR. Am. J. Physiol. 260(6 Pt 2), F890\u2013F897 (1991).","journal-title":"Am. J. Physiol."},{"issue":"6","key":"94221_CR52","doi-asserted-by":"publisher","first-page":"F1168","DOI":"10.1152\/ajprenal.00463.2011","volume":"301","author":"RR Singh","year":"2011","unstructured":"Singh, R. R. et al. Urine-concentrating defects exacerbate with age in male offspring with a low-nephron endowment. Am. J. Physiol. Renal Physiol. 301(6), F1168\u2013F1176. https:\/\/doi.org\/10.1152\/ajprenal.00463.2011 (2011) ((Epub 2011 Sep 14)).","journal-title":"Am. J. Physiol. Renal Physiol."},{"issue":"5","key":"94221_CR53","doi-asserted-by":"publisher","first-page":"H958","DOI":"10.1152\/ajpheart.00299.2019","volume":"317","author":"H Zheng","year":"2019","unstructured":"Zheng, H. et al. Renal denervation improves sodium excretion in rats with chronic heart failure: Effects on expression of renal ENaC and AQP2. Am. J. Physiol. Heart Circ. Physiol. 317(5), H958-h968 (2019).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"issue":"11","key":"94221_CR54","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1042\/CS20090479","volume":"118","author":"RR Singh","year":"2010","unstructured":"Singh, R. R. et al. Reduced nephron endowment due to fetal uninephrectomy impairs renal sodium handling in male sheep. Clin. Sci. (Lond.) 118(11), 669\u2013680. https:\/\/doi.org\/10.1042\/CS20090479 (2010).","journal-title":"Clin. Sci. (Lond.)"},{"issue":"8","key":"94221_CR55","doi-asserted-by":"publisher","first-page":"F848","DOI":"10.1152\/ajprenal.00515.2014","volume":"308","author":"RB Pontes","year":"2015","unstructured":"Pontes, R. B. et al. Renal nerve stimulation leads to the activation of the Na+\/H+ exchanger isoform 3 via angiotensin II type I receptor. Am. J. Physiol. Renal Physiol. 308(8), F848\u2013F856 (2015).","journal-title":"Am. J. Physiol. Renal Physiol."},{"issue":"3","key":"94221_CR56","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/0002-9343(86)90291-3","volume":"81","author":"NK Hollenberg","year":"1986","unstructured":"Hollenberg, N. K. et al. Abnormal renal sodium handling in essential hypertension. Relation to failure of renal and adrenal modulation of responses to angiotensin II. Am. J. Med. 81(3), 412\u2013418 (1986).","journal-title":"Am. J. Med."},{"issue":"2","key":"94221_CR57","doi-asserted-by":"publisher","first-page":"R428","DOI":"10.1152\/ajpregu.90753.2008","volume":"296","author":"P Bie","year":"2009","unstructured":"Bie, P., Molstrom, S. & Wamberg, S. Normotensive sodium loading in conscious dogs: Regulation of renin secretion during beta-receptor blockade. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296(2), R428\u2013R435. https:\/\/doi.org\/10.1152\/ajpregu.90753.2008 (2009) ((Epub 2008 Dec 10)).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"issue":"2","key":"94221_CR58","doi-asserted-by":"publisher","first-page":"R436","DOI":"10.1152\/ajpregu.90754.2008","volume":"296","author":"S Molstrom","year":"2009","unstructured":"Molstrom, S. et al. Normotensive sodium loading in normal man: Regulation of renin secretion during beta-receptor blockade. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296(2), R436\u2013R445. https:\/\/doi.org\/10.1152\/ajpregu.90754.2008 (2009) ((Epub 2008 Dec 10)).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"issue":"6","key":"94221_CR59","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1161\/HYPERTENSIONAHA.107.087213","volume":"49","author":"M Carlstr\u00f6m","year":"2007","unstructured":"Carlstr\u00f6m, M. et al. Uninephrectomy in young age or chronic salt loading causes salt-sensitive hypertension in adult rats. Hypertension 49(6), 1342\u20131350 (2007).","journal-title":"Hypertension"},{"issue":"5","key":"94221_CR60","first-page":"807","volume":"88","author":"P Ylitalo","year":"1976","unstructured":"Ylitalo, P. et al. Effects of varying sodium intake on blood pressure and renin-angiotensin system in subtotally nephrectomized rats. J. Lab. Clin. Med. 88(5), 807\u2013816 (1976).","journal-title":"J. Lab. Clin. Med."},{"issue":"7639","key":"94221_CR61","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S0140-6736(70)90404-6","volume":"1","author":"DJ Warren","year":"1970","unstructured":"Warren, D. J. & Ferris, T. F. Renin secretion in renal hypertension. Lancet 1(7639), 159\u2013162 (1970).","journal-title":"Lancet"},{"issue":"3","key":"94221_CR62","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/0002-9343(73)90137-X","volume":"55","author":"MA Schalekamp","year":"1973","unstructured":"Schalekamp, M. A. et al. Hypertension in chronic renal failure. An abnormal relation between sodium and the renin\u2013angiotensin system. Am. J. Med. 55(3), 379\u2013390 (1973).","journal-title":"Am. J. Med."},{"issue":"5","key":"94221_CR63","first-page":"1426","volume":"45","author":"J Schnermann","year":"1986","unstructured":"Schnermann, J. & Briggs, J. Role of the renin-angiotensin system in tubuloglomerular feedback. Fed. Proc. 45(5), 1426\u20131430 (1986).","journal-title":"Fed. Proc."},{"issue":"1","key":"94221_CR64","doi-asserted-by":"publisher","first-page":"e00208","DOI":"10.1002\/phy2.208","volume":"2","author":"YR Lankadeva","year":"2014","unstructured":"Lankadeva, Y. R. et al. Impaired ability to modulate glomerular filtration rate in aged female sheep following fetal uninephrectomy. Physiol. Rep. 2(1), e00208 (2014).","journal-title":"Physiol. Rep."},{"key":"94221_CR65","doi-asserted-by":"publisher","first-page":"S40","DOI":"10.1046\/j.1523-1755.1998.06708.x","volume":"67","author":"J Schnermann","year":"1998","unstructured":"Schnermann, J. et al. Tubuloglomerular feedback: New concepts and developments. Kidney Int. Suppl. 67, S40\u2013S45 (1998).","journal-title":"Kidney Int. Suppl."},{"issue":"1","key":"94221_CR66","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/j.1748-1716.1995.tb09832.x","volume":"153","author":"C Thorup","year":"1995","unstructured":"Thorup, C. et al. Acute renal denervation causes time-dependent resetting of the tubuloglomerular feedback mechanism. Acta Physiol. Scand. 153(1), 43\u201349 (1995).","journal-title":"Acta Physiol. Scand."},{"issue":"2","key":"94221_CR67","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1046\/j.1365-201X.1996.433168000.x","volume":"156","author":"C Thorup","year":"1996","unstructured":"Thorup, C. et al. Effects of acute and chronic unilateral renal denervation on the tubuloglomerular feedback mechanism. Acta Physiol. Scand. 156(2), 139\u2013145 (1996).","journal-title":"Acta Physiol. Scand."},{"issue":"2","key":"94221_CR68","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1038\/ki.1994.52","volume":"45","author":"ME Rosenberg","year":"1994","unstructured":"Rosenberg, M. E. et al. The paradox of the renin-angiotensin system in chronic renal disease. Kidney Int. 45(2), 403\u2013410 (1994).","journal-title":"Kidney Int."},{"issue":"2","key":"94221_CR69","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/S0002-9440(10)65139-5","volume":"155","author":"RE Gilbert","year":"1999","unstructured":"Gilbert, R. E. et al. Pathological expression of renin and angiotensin II in the renal tubule after subtotal nephrectomy. Implications for the pathogenesis of tubulointerstitial fibrosis. Am. J. Pathol. 155(2), 429\u2013440 (1999).","journal-title":"Am. J. Pathol."},{"issue":"1","key":"94221_CR70","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1681\/ASN.V9172","volume":"9","author":"HN Ibrahim","year":"1998","unstructured":"Ibrahim, H. N. & Hostetter, T. H. The renin\u2013aldosterone axis in two models of reduced renal mass in the rat. J. Am. Soc. Nephrol. 9(1), 72\u201376 (1998).","journal-title":"J. Am. Soc. Nephrol."},{"key":"94221_CR71","doi-asserted-by":"publisher","first-page":"26777","DOI":"10.1038\/srep26777","volume":"6","author":"RR Singh","year":"2016","unstructured":"Singh, R. R. et al. Renal nitric oxide deficiency and chronic kidney disease in young sheep born with a solitary functioning kidney. Sci. Rep. 6, 26777 (2016).","journal-title":"Sci. Rep."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-94221-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-94221-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-94221-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T11:20:59Z","timestamp":1670066459000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-94221-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,20]]},"references-count":71,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["94221"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-94221-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,20]]},"assertion":[{"value":"29 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Prof Kate Denton and has received honoraria from Medtronic for presentations. Dr Schlaich is an investigator in studies sponsored by Medtronic and his laboratories have received research funding from Medtronic. Dr Schlaich serves on scientific advisory boards for Abbott (formerly Solvay) Pharmaceuticals, Boehringer Ingelheim, Novartis Pharmaceuticals, and Medtronic and has received honoraria and travel support from Abbott, Boehringer Ingelheim, Servier, Novartis, and Medtronic. Prof May has received honoraria and travel support for presentations from Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14795"}}