{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:49:52Z","timestamp":1768589392352,"version":"3.49.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We investigated the impact of short-acting and extended release nifedipine on sympathetic activity using radiotracer methodology in patients with stable coronary artery disease in order to more accurately document the response of the sympathetic nervous system to different formulations of this dihydropyridine calcium channel antagonist. Participants were randomized to placebo, short-acting or extended release nifedipine for 7\u201310 days. On the final day, systemic blood pressure, cardiac filling pressures, cardiac output, plasma norepinephrine (NE) and total body NE spillover were measured at baseline (time 0) and repeated at intervals for 6\u2009hours. There were no differences in baseline measures between groups. Following the morning dose of study medication there were no changes in hemodynamics or sympathetic activity in the placebo group. However, there was a significant fall in blood pressure and a significant increase in total body NE spillover in both nifedipine groups. Importantly, the increase in sympathetic activity in response to short-acting nifedipine began earlier (30\u2009minutes) and was much greater than that observed in the extended release group, which occurred later (270\u2009minutes). These findings confirm that sustained therapy with nifedipine is associated with activation of the sympathetic nervous system which is dependent on the pharmacokinetics of the formulation.<\/jats:p>","DOI":"10.1038\/s41598-019-56890-1","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T11:03:17Z","timestamp":1579863797000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Comparison of short-acting versus extended-release nifedipine: Effects on hemodynamics and sympathetic activity in patients with stable coronary artery disease"],"prefix":"10.1038","volume":"10","author":[{"given":"John D.","family":"Parker","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"D\u2019 Iorio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John S.","family":"Floras","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corey B.","family":"Toal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,1,24]]},"reference":[{"issue":"Suppl 1","key":"56890_CR1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3109\/08037051.2012.690615","volume":"21","author":"CB Toal","year":"2012","unstructured":"Toal, C. B., Meredith, P. A. & Elliott, H. L. Long-acting dihydropyridine calcium-channel blockers and sympathetic nervous system activity in hypertension: a literature review comparing amlodipine and nifedipine GITS. Blood Press. 21(Suppl 1), 3\u201310 (2012).","journal-title":"Blood Press."},{"key":"56890_CR2","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1097\/00004872-199816090-00017","volume":"16","author":"J de Champlain","year":"1998","unstructured":"de Champlain, J. et al. Different effects of nifedipine and amlodipine on circulating catecholamine levels in essential hypertensive patients. J. Hypertens. 16, 1357\u20131369 (1998).","journal-title":"J. Hypertens."},{"key":"56890_CR3","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0895-7061(00)01267-X","volume":"14","author":"JA Diamond","year":"2001","unstructured":"Diamond, J. A. et al. Comparison of two calcium blockers on hemodynamics, left ventricular mass, and coronary vasodilatory in advanced hypertension. Am. J. Hypertens. 14, 231\u2013240 (2001).","journal-title":"Am. J. Hypertens."},{"key":"56890_CR4","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/S0895-7061(03)00901-4","volume":"16","author":"R Fogari","year":"2003","unstructured":"Fogari, R. et al. Differential effects of lercanidipine and nifedipine GITS on plasma norepinephrine in chronic treatment of hypertension. Am. J. Hypertens. 16, 596\u2013599 (2003).","journal-title":"Am. J. Hypertens."},{"key":"56890_CR5","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.amjhyper.2004.11.020","volume":"18","author":"R Fogari","year":"2005","unstructured":"Fogari, R. et al. Effect of telmisartan\/hydrochlorothiazide combination versus nifedipine GITS on ambulatory blood pressure and sympathetic activation. Am. J. Hypertens. 18, 577\u2013583, https:\/\/doi.org\/10.1016\/j.amjhyper.2004.11.020 (2005).","journal-title":"Am. J. Hypertens."},{"key":"56890_CR6","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1097\/00004872-200018120-00023","volume":"18","author":"R Fogari","year":"2000","unstructured":"Fogari, R. et al. Effects of different dihydropyridine calcium antagonists on plasma norepinephrine in essential hypertension. J. Hypertens. 18, 1871\u20131875 (2000).","journal-title":"J. Hypertens."},{"key":"56890_CR7","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1161\/01.HYP.26.1.143","volume":"26","author":"MT Kailasam","year":"1995","unstructured":"Kailasam, M. T. et al. Divergent effects of dihydropyridine and phenylalkylamine calcium channel antagonist classes on autonomic function in human hypertension. Hypertension 26, 143\u2013149 (1995).","journal-title":"Hypertension"},{"key":"56890_CR8","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S0735-1097(86)80503-4","volume":"7","author":"W Kiowski","year":"1986","unstructured":"Kiowski, W., Erne, P., Bertel, O., Bolli, P. & Buhler, F. Acute and chronic sympathetic reflex activation and antihypertensive response to nifedipine. J. Am. Coll. Cardiol. 7, 344\u2013348 (1986).","journal-title":"J. Am. Coll. Cardiol."},{"key":"56890_CR9","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/clpt.1984.105","volume":"35","author":"CH Kleinbloesem","year":"1984","unstructured":"Kleinbloesem, C. H., van Brummelen, P., van de Linde, J. A., Voogd, P. J. & Breimer, D. D. Nifedipine: kinetics and dynamics in healthy subjects. Clin. Pharmacol. Ther. 35, 742\u2013749 (1984).","journal-title":"Clin. Pharmacol. Ther."},{"key":"56890_CR10","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/clpt.1984.194","volume":"36","author":"CH Kleinbloesem","year":"1984","unstructured":"Kleinbloesem, C. H., van Harten, J., de Leede, L. G., van Brummelen, P. & Breimer, D. D. Nifedipine kinetics and dynamics during rectal infusion to steady state with an osmotic system. Clin. Pharmacol. Ther. 36, 396\u2013401 (1984).","journal-title":"Clin. Pharmacol. Ther."},{"key":"56890_CR11","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/00005344-198603000-00011","volume":"8","author":"K Laederach","year":"1986","unstructured":"Laederach, K., Weidmann, P., Lauener, F., Gerber, A. & Ziegler, W. H. Comparative acute effects of the calcium channel blockers tiapamil, nisoldipine, and nifedipine on blood pressure and some regulatory factors in normal and hypertensive subjects. J. Cardiovasc. Pharmacol. 8, 294\u2013302 (1986).","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"56890_CR12","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0002-8703(05)80085-7","volume":"119","author":"S Bekheit","year":"1990","unstructured":"Bekheit, S. et al. Use of heart rate spectral analysis to study the effects of calcium channel blockers on sympathetic activity after myocardial infarction. Am. Heart J. 119, 79\u201385 (1990).","journal-title":"Am. Heart J."},{"key":"56890_CR13","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/hr.2009.18","volume":"32","author":"M Fukuda","year":"2009","unstructured":"Fukuda, M. et al. Influence of nifedipine coat-core and amlodipine on systemic arterial stiffness modulated by sympathetic and parasympathetic activity in hypertensive patients. Hypertens. Res. 32, 392\u2013398 (2009).","journal-title":"Hypertens. Res."},{"key":"56890_CR14","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1097\/HJH.0b013e3280104dba","volume":"25","author":"M Lindqvist","year":"2007","unstructured":"Lindqvist, M., Kahan, T., Melcher, A., Ekholm, M. & Hjemdahl, P. Long-term calcium antagonist treatment of human hypertension with mibefradil or amlodipine increases sympathetic nerve activity. J. Hypertens. 25, 169\u2013175 (2007).","journal-title":"J. Hypertens."},{"key":"56890_CR15","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1097\/00004872-200102000-00015","volume":"19","author":"AM Pellizzer","year":"2001","unstructured":"Pellizzer, A. M., Kamen, P. W., Esler, M. D., Lim, S. & Krum, H. Comparative effects of mibefradil and nifedipine gastrointestinal transport system on autonomic function in patients with mild to moderate essential hypertension. J. Hypertens. 19, 279\u2013285 (2001).","journal-title":"J. Hypertens."},{"key":"56890_CR16","first-page":"65","volume":"21","author":"H Sato","year":"2001","unstructured":"Sato, H. et al. Effects of nifedipine retard on heart rate and autonomic balance in patients with ischemic heart disease. Int. J. Clin. Pharmacol. Res. 21, 65\u201371 (2001).","journal-title":"Int. J. Clin. Pharmacol. Res."},{"key":"56890_CR17","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1136\/hrt.70.3.252","volume":"70","author":"MW Schweizer","year":"1993","unstructured":"Schweizer, M. W. et al. Heart rate variability in time and frequency domains: effects of gallopamil, nifedipine, and metoprolol compared with placebo. Br. Heart J. 70, 252\u2013258 (1993).","journal-title":"Br. Heart J."},{"key":"56890_CR18","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1161\/01.HYP.0000013264.41234.24","volume":"39","author":"C Binggeli","year":"2002","unstructured":"Binggeli, C., Corti, R., Sudano, I., Luscher, T. F. & Noll, G. Effects of chronic calcium channel blockade on sympathetic nerve activity in hypertension. Hypertension 39, 892\u2013896 (2002).","journal-title":"Hypertension"},{"key":"56890_CR19","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1161\/01.CIR.80.2.285","volume":"80","author":"DW Ferguson","year":"1989","unstructured":"Ferguson, D. W. & Hayes, D. W. Nifedipine potentiates cardiopulmonary baroreflex control of sympathetic nerve activity in healthy humans. Direct evidence from microneurographic studies. Circulation 80, 285\u2013298 (1989).","journal-title":"Circulation"},{"key":"56890_CR20","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1097\/HJH.0000000000000270","volume":"32","author":"J Inomata","year":"2014","unstructured":"Inomata, J. et al. Differential effects of azelnidipine and amlodipine on sympathetic nerve activity in patients with primary hypertension. J. Hypertens. 32, 1898\u20131904 (2014).","journal-title":"J. Hypertens."},{"key":"56890_CR21","first-page":"S17","volume":"16","author":"G Noll","year":"1998","unstructured":"Noll, G., Wenzel, R. R., Shaw, S. & Luscher, T. F. Calcium antagonists and sympathetic nerve activation: are there differences between classes? J. Hypertens. Suppl. 16, S17\u201324 (1998).","journal-title":"J. Hypertens. Suppl."},{"key":"56890_CR22","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1097\/00004872-200405000-00028","volume":"22","author":"M Ruzicka","year":"2004","unstructured":"Ruzicka, M., Coletta, E., Floras, J. & Leenen, F. H. Effects of low-dose nifedipine GITS on sympathetic activity in young and older patients with hypertension. J. Hypertens. 22, 1039\u20131044 (2004).","journal-title":"J. Hypertens."},{"key":"56890_CR23","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1097\/00004872-200206000-00026","volume":"20","author":"J Struck","year":"2002","unstructured":"Struck, J. et al. Effects of selective angiotensin II receptor blockade on sympathetic nerve activity in primary hypertensive subjects. J. Hypertens. 20, 1143\u20131149 (2002).","journal-title":"J. Hypertens."},{"key":"56890_CR24","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/S0735-1097(97)00095-8","volume":"29","author":"RR Wenzel","year":"1997","unstructured":"Wenzel, R. R. et al. Differential activation of cardiac and peripheral sympathetic nervous system by nifedipine: role of pharmacokinetics. J. Am. Coll. Cardiol. 29, 1607\u20131614 (1997).","journal-title":"J. Am. Coll. Cardiol."},{"key":"56890_CR25","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/0895-7061(95)00163-J","volume":"8","author":"SR Goldsmith","year":"1995","unstructured":"Goldsmith, S. R. Effect of amlodipine and felodipine on sympathetic activity and baroreflex function in normal humans. Am. J. Hypertens. 8, 902\u2013908 (1995).","journal-title":"Am. J. Hypertens."},{"key":"56890_CR26","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1161\/01.HYP.24.3.287","volume":"24","author":"M Lindqvist","year":"1994","unstructured":"Lindqvist, M., Kahan, T., Melcher, A. & Hjemdahl, P. Acute and chronic calcium antagonist treatment elevates sympathetic activity in primary hypertension. Hypertension 24, 287\u2013296 (1994).","journal-title":"Hypertension"},{"key":"56890_CR27","first-page":"S571","volume":"5","author":"AR Lucarini","year":"1987","unstructured":"Lucarini, A. R. & Salvetti, A. Haemodynamic (systemic and renal) and humoral interactions between nicardipine and domperidone in hypertensives. J. Hypertens. Suppl. 5, S571\u2013574 (1987).","journal-title":"J. Hypertens. Suppl."},{"key":"56890_CR28","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/clpt.1987.62","volume":"41","author":"KS Ryman","year":"1987","unstructured":"Ryman, K. S., Kubo, S. H., Shaknovich, A. & Cody, R. J. Influence of baseline hemodynamic status and sympathetic activity on the response to nicardipine, a new dihydropyridine, in patients with hypertension or chronic congestive heart failure. Clin. Pharmacol. Ther. 41, 483\u2013489 (1987).","journal-title":"Clin. Pharmacol. Ther."},{"key":"56890_CR29","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1067\/mcp.2001.113406","volume":"69","author":"I Ragueneau","year":"2001","unstructured":"Ragueneau, I. et al. Comparison of sympathetic modulation induced by single oral doses of mibefradil, amlodipine, and nifedipine in healthy volunteers. Clin. Pharmacol. Ther. 69, 122\u2013129 (2001).","journal-title":"Clin. Pharmacol. Ther."},{"key":"56890_CR30","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0002-8703(97)70101-7","volume":"134","author":"SR Goldsmith","year":"1997","unstructured":"Goldsmith, S. R. Effect of amlodipine on norepinephrine kinetics and baroreflex function in patients with congestive heart failure. Am. Heart J. 134, 13\u201319 (1997).","journal-title":"Am. Heart J."},{"key":"56890_CR31","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s002280050362","volume":"53","author":"M Sasaguri","year":"1997","unstructured":"Sasaguri, M. et al. Amlodipine lowers blood pressure without increasing sympathetic activity or activating the renin-angiotensin system in patients with essential hypertension. Eur. J. Clin. Pharmacol. 53, 197\u2013201 (1997).","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"56890_CR32","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1097\/00005344-199705000-00017","volume":"29","author":"D Lucini","year":"1997","unstructured":"Lucini, D., Mela, G. S., Malliani, A. & Pagani, M. Evidence of increased sympathetic vasomotor drive with shorter acting dihydropyridine calcium channel antagonists in human hypertension: a study using spectral analysis of RR interval and systolic arterial pressure variability. J. Cardiovasc. Pharmacol. 29, 676\u2013683 (1997).","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"56890_CR33","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/clpt.1992.102","volume":"52","author":"L Donati","year":"1992","unstructured":"Donati, L., Buhler, F. R., Beretta-Piccoli, C., Kusch, F. & Heinen, G. Antihypertensive mechanism of amlodipine in essential hypertension: role of pressor reactivity to norepinephrine and angiotensin II. Clin. Pharmacol. Ther. 52, 50\u201359 (1992).","journal-title":"Clin. Pharmacol. Ther."},{"key":"56890_CR34","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/01.hjh.0000198032.07224.c3","volume":"24","author":"FH Leenen","year":"2006","unstructured":"Leenen, F. H., Coletta, E. & White, R. Sympatho-excitatory responses to once-daily dihydropyridines in young versus older hypertensive patients: amlodipine versus felodipine extended release. J. Hypertens. 24, 177\u2013184 (2006).","journal-title":"J. Hypertens."},{"key":"56890_CR35","doi-asserted-by":"crossref","first-page":"202","DOI":"10.5414\/CP201603","volume":"50","author":"CB Toal","year":"2012","unstructured":"Toal, C. B., Meredith, P. A. & Elliott, H. L. Once daily nifedipine: the formulation dictates the pharmacokinetic characteristics and the therapeutic responses. Int. J. Clin. Pharmacol. Ther. 50, 202\u2013217 (2012).","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"56890_CR36","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0002-8703(85)90584-8","volume":"109","author":"JL Rouleau","year":"1985","unstructured":"Rouleau, J. L. et al. Myocardial catecholamine balance during angina: effects of calcium entry blockers, verapamil and nifedipine. Am. Heart J. 109, 201\u2013209 (1985).","journal-title":"Am. Heart J."},{"key":"56890_CR37","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1291\/hypres.23.7","volume":"23","author":"S Hoshide","year":"2000","unstructured":"Hoshide, S., Kario, K., Mitsuhashi, T., Ikeda, U. & Shimada, K. Is there any difference between intermediate-acting and long-acting calcium antagonists in diurnal blood pressure and autonomic nervous activity in hypertensive coronary artery disease patients? Hypertens. Res. 23, 7\u201314 (2000).","journal-title":"Hypertens. Res."},{"key":"56890_CR38","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1093\/oxfordjournals.eurheartj.a059729","volume":"11","author":"V Mitrovic","year":"1990","unstructured":"Mitrovic, V. et al. Effects of the calcium antagonist, isradipine, and nifedipine on resting and exercise haemodynamics and the neurohumoral system in patients with stable chronic angina. Eur. Heart J. 11, 454\u2013461 (1990).","journal-title":"Eur. Heart J."},{"key":"56890_CR39","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1161\/01.CIR.92.5.1326","volume":"92","author":"CD Furberg","year":"1995","unstructured":"Furberg, C. D., Psaty, B. M. & Meyer, J. V. Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. Circulation 92, 1326\u20131331 (1995).","journal-title":"Circulation"},{"key":"56890_CR40","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1001\/jama.1997.03540330061036","volume":"277","author":"BM Psaty","year":"1997","unstructured":"Psaty, B. M. et al. Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and meta-analysis. JAMA 277, 739\u2013745 (1997).","journal-title":"JAMA"},{"key":"56890_CR41","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0140-6736(04)16980-8","volume":"364","author":"PA Poole-Wilson","year":"2004","unstructured":"Poole-Wilson, P. A. et al. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial. Lancet 364, 849\u2013857 (2004).","journal-title":"Lancet"},{"key":"56890_CR42","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/S0140-6736(00)02527-7","volume":"356","author":"MJ Brown","year":"2000","unstructured":"Brown, M. J. et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 356, 366\u2013372 (2000).","journal-title":"Lancet"},{"key":"56890_CR43","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1161\/01.CIR.94.12.3161","volume":"94","author":"GE Newton","year":"1996","unstructured":"Newton, G. E. & Parker, J. D. Cardiac sympathetic responses to acute vasodilation. Normal ventricular function versus congestive heart failure. Circulation 94, 3161\u20133167 (1996).","journal-title":"Circulation"},{"key":"56890_CR44","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1161\/01.CIR.94.3.353","volume":"94","author":"GE Newton","year":"1996","unstructured":"Newton, G. E. & Parker, J. D. Acute effects of beta 1-selective and nonselective beta-adrenergic receptor blockade on cardiac sympathetic activity in congestive heart failure. Circulation 94, 353\u2013358 (1996).","journal-title":"Circulation"},{"key":"56890_CR45","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0378-4347(88)80011-2","volume":"425","author":"BJ Schmid","year":"1988","unstructured":"Schmid, B. J., Perry, H. E. & Idle, J. R. Determination of nifedipine and its three principal metabolites in plasma and urine by automated electron-capture capillary gas chromatography. J. Chromatogr. 425, 107\u2013119 (1988).","journal-title":"J. Chromatogr."},{"key":"56890_CR46","first-page":"1285","volume":"18","author":"FH Leenen","year":"2002","unstructured":"Leenen, F. H., Myers, M. G., Joyner, C. D. & Toal, C. B. Differential effects of once-daily antihypertensive drugs on blood pressure, left ventricular mass and sympathetic activity: Nifedipine-GITS versus felodipine-ER versus enalapril. Can. J. Cardiol. 18, 1285\u20131293 (2002).","journal-title":"Can. J. Cardiol."},{"key":"56890_CR47","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/j.1365-2125.2007.03082.x","volume":"65","author":"MJ Brown","year":"2008","unstructured":"Brown, M. J. & Toal, C. B. Formulation of long-acting nifedipine tablets influences the heart rate and sympathetic nervous system response in hypertensive patients. Br. J. Clin. Pharmacol. 65, 646\u2013652 (2008).","journal-title":"Br. J. Clin. Pharmacol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-56890-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-56890-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-56890-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T05:54:36Z","timestamp":1670306076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-56890-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,24]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["56890"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-56890-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,24]]},"assertion":[{"value":"5 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was supported by a funding from Bayer, Canada. Apart from this funding the authors have no competing interests to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"565"}}