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Current Vascular Pharmacology

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ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

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Research Article

Aerobic Physical Exercise is Essential for Cardiac Autonomic Regulation in Hypertensive Patients Undergoing Chronic Treatment with Renin- Angiotensin System Inhibitors

Author(s): Tábata de Paula Facioli, Stella Vieira Philbois, Jens Tank, Ada Clarice Gastaldi, Bruno Augusto Aguilar, Ana Catarine da Veiga Oliveira, Lucas Dalvit Ferreira and Hugo Celso Dutra de Souza*

Volume 21, Issue 4, 2023

Published on: 03 July, 2023

Page: [274 - 284] Pages: 11

DOI: 10.2174/1570161121666230522105458

Price: $65

Abstract

Background: Hypertension treatment with renin-angiotensin system inhibitors (RASi) presents contradictions about the recovery of damage in cardiovascular autonomic modulation characterized by reduced heart rate variability (HRV) and increased blood pressure variability (BPV). Conversely, the association of RASi with physical training can influence achievements in cardiovascular autonomic modulation.

Objective: To investigate the effects of aerobic physical training on hemodynamics and cardiovascular autonomic modulation in hypertensive volunteers untreated and treated with RASi.

Methods: A non-randomized controlled trial in which 54 men (≅ 40-60 years old) with a history of hypertension for >2 years were allocated in accordance with their characteristics into three groups: untreated (Control; n=16), treated with type 1 angiotensin II (AT1) receptor blocker (losartan; n=21), and treated with angiotensin-converting enzyme inhibitor (enalapril; n=17). All participants underwent hemodynamic, metabolic, and cardiovascular autonomic evaluation using baroreflex sensitivity (BRS) and spectral analysis of HRV and BPV, before and after 16 weeks of supervised aerobic physical training.

Results: The volunteers treated with RASi had lower BPV and HRV, both in the supine position and in the tilt test, with the losartan group having the lowest values. Aerobic physical training increased HRV and BRS in all groups. However, the association of enalapril with physical training appears to be more prominent.

Conclusion: Long-term treatment with enalapril and losartan may harm the autonomic modulation of HRV and BRS. Aerobic physical training is essential to promote positive adjustments in the autonomic modulation of HRV and BRS in hypertensive patients treated with RASi, especially with enalapril.

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[1]
Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018; 39(33): 3021-104.
[http://dx.doi.org/10.1093/eurheartj/ehy339] [PMID: 30165516]
[2]
Alwardat N, Di Renzo L, de Miranda RC, Alwardat S, Sinibaldi Salimei P, De Lorenzo A. Association between hypertension and metabolic disorders among elderly patients in North Jordan. Diabetes Metab Syndr 2018; 12(5): 661-6.
[http://dx.doi.org/10.1016/j.dsx.2018.04.011] [PMID: 29678607]
[3]
Laterza MC, de Matos LDNJ, Trombetta IC, et al. Exercise training restores baroreflex sensitivity in never-treated hypertensive patients. Hypertension 2007; 49(6): 1298-306.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.106.085548] [PMID: 17438307]
[4]
Weinstock M, Gorodetsky E. Comparison of the effects of angiotensin II, losartan, and enalapril on baroreflex control of heart rate in conscious rabbits. J Cardiovasc Pharmacol 1995; 25(3): 501-7.
[http://dx.doi.org/10.1097/00005344-199503000-00024] [PMID: 7769820]
[5]
Klein IHHT, Ligtenberg G, Oey PL, Koomans HA, Blankestijn PJ. Enalapril and losartan reduce sympathetic hyperactivity in patients with chronic renal failure. J Am Soc Nephrol 2003; 14(2): 425-30.
[http://dx.doi.org/10.1097/01.ASN.0000045049.72965.B7] [PMID: 12538743]
[6]
Karas M, Lacourcière Y, LeBlanc AR, et al. Effect of the renin-angiotensin system or calcium channel blockade on the circadian variation of heart rate variability, blood pressure and circulating catecholamines in hypertensive patients. J Hypertens 2005; 23(6): 1251-60.
[http://dx.doi.org/10.1097/01.hjh.0000170389.69202.53] [PMID: 15894902]
[7]
Guasti L, Petrozzino MR, Mainardi LT, et al. Autonomic function and baroreflex sensitivity during angiotensin-converting enzyme inhibition or angiotensin II AT-1 receptor blockade in essential hypertensive patients. Acta Cardiol 2001; 56(5): 289-95.
[http://dx.doi.org/10.2143/AC.56.5.2005689] [PMID: 11712824]
[8]
Fu Q, Shook RP, Okazaki K, et al. Vasomotor sympathetic neural control is maintained during sustained upright posture in humans. J Physiol 2006; 577(2): 679-87.
[http://dx.doi.org/10.1113/jphysiol.2006.118158] [PMID: 17008377]
[9]
Lewandowski J, Abramczyk P, Dobosiewicz A, Bidiuk J, Sinski M, Gaciong Z. The effect of enalapril and telmisartan on clinical and biochemical indices of sympathetic activity in hypertensive patients. Clin Exp Hypertens 2008; 30(5): 423-32.
[http://dx.doi.org/10.1080/10641960802279132] [PMID: 18633764]
[10]
Milovanovic B, Trifunovic D, Djuric D. Autonomic nervous system adjustment (ANSA) in patients with hypertension treated with enalapril. Acta Physiol Hung 2011; 98(1): 71-84.
[http://dx.doi.org/10.1556/APhysiol.98.2011.1.9] [PMID: 21388933]
[11]
Heusser K, Vitkovsky J, Schmieder RE, Schobel HP. AT1 antagonism by eprosartan lowers heart rate variability and baroreflex gain. Auton Neurosci 2003; 107(1): 45-51.
[http://dx.doi.org/10.1016/S1566-0702(03)00053-5] [PMID: 12927226]
[12]
Heusser K, Vitkovsky J, Raasch W, Schmieder RE, Schobel HP. Elevation of sympathetic activity by eprosartan in young male subjects. Am J Hypertens 2003; 16(8): 658-64.
[http://dx.doi.org/10.1016/S0895-7061(03)00917-8] [PMID: 12878372]
[13]
Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2017 focused update of the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk. J Am Coll Cardiol 2017; 70(14): 1785-822.
[http://dx.doi.org/10.1016/j.jacc.2017.07.745] [PMID: 28886926]
[14]
Carter JB, Banister EW, Blaber AP. Effect of endurance exercise on autonomic control of heart rate. Sports Med 2003; 33(1): 33-46.
[http://dx.doi.org/10.2165/00007256-200333010-00003] [PMID: 12477376]
[15]
Wu NN, Tian H, Chen P, Wang D, Ren J, Zhang Y. Physical exercise and selective autophagy: Benefit and risk on cardiovascular health. Cells 2019; 8(11): 1436.
[http://dx.doi.org/10.3390/cells8111436] [PMID: 31739509]
[16]
Cornelissen VA, Fagard RH. Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors. Hypertension 2005; 46(4): 667-75.
[http://dx.doi.org/10.1161/01.HYP.0000184225.05629.51] [PMID: 16157788]
[17]
Piotrowicz E, Baranowski R, Piotrowska M. Zieliński T, Piotrowicz R. Variable effects of physical training of heart rate variability, heart rate recovery, and heart rate turbulence in chronic heart failure. Pacing Clin Electrophysiol 2009; 32 (Suppl. 1): S113-5.
[http://dx.doi.org/10.1111/j.1540-8159.2008.02266.x] [PMID: 19250071]
[18]
Sloan RP, Shapiro PA, DeMeersman RE, et al. The effect of aerobic training and cardiac autonomic regulation in young adults. Am J Public Health 2009; 99(5): 921-8.
[http://dx.doi.org/10.2105/AJPH.2007.133165] [PMID: 19299682]
[19]
Collier SR, Kanaley JA, Carhart R Jr, et al. Cardiac autonomic function and baroreflex changes following 4 weeks of resistance versus aerobic training in individuals with pre-hypertension. Acta Physiol 2009; 195(3): 339-48.
[http://dx.doi.org/10.1111/j.1748-1716.2008.01897.x] [PMID: 18774947]
[20]
Cozza IC, Di Sacco THR, Mazon JH, et al. Physical exercise improves cardiac autonomic modulation in hypertensive patients independently of angiotensin-converting enzyme inhibitor treatment. Hypertens Res 2012; 35(1): 82-7.
[http://dx.doi.org/10.1038/hr.2011.162] [PMID: 21956728]
[21]
Oggionni G, Spataro A, Pelliccia A, Malacarne M, Pagani M, Lucini D. Left ventricular hypertrophy in world class elite athletes is associated with signs of improved cardiac autonomic regulation. Eur J Prev Cardiol 2019; 28: 2047487319830534.
[PMID: 30755021]
[22]
Santulli G, Ciccarelli M, Trimarco B, Iaccarino G. Physical activity ameliorates cardiovascular health in elderly subjects: The functional role of the β adrenergic system. Front Physiol 2013; 4: 209.
[http://dx.doi.org/10.3389/fphys.2013.00209] [PMID: 23964243]
[23]
Lackland DT, Voeks JH. Metabolic syndrome and hypertension: Regular exercise as part of lifestyle management. Curr Hypertens Rep 2014; 16(11): 492.
[http://dx.doi.org/10.1007/s11906-014-0492-2] [PMID: 25190022]
[24]
Souza HCD, De Araújo JE, Martins-Pinge MC, Cozza IC, Martins-Dias DP. Nitric oxide synthesis blockade reduced the baroreflex sensitivity in trained rats. Auton Neurosci 2009; 150(1-2): 38-44.
[http://dx.doi.org/10.1016/j.autneu.2009.04.007] [PMID: 19443278]
[25]
Prakash ES, Sethuraman KR, Narayan SK, Narayan SK. Cardiovascular autonomic regulation in subjects with normal blood pressure, high-normal blood pressure and recent-onset hypertension. Clin Exp Pharmacol Physiol 2005; 32(5-6): 488-94.
[http://dx.doi.org/10.1111/j.1440-1681.2005.04218.x] [PMID: 15854164]
[26]
Doğru MT, Simşek V, Şahin O, Özer N. Differences in autonomic activity in individuals with optimal, normal, and high-normal blood pressure levels. Turk Kardiyol Dern Ars 2010; 38(3): 182-8.
[PMID: 20675995]
[27]
Celovská D, Stasko J, Gonsorcík J, Dukát A. The value of baroreflex sensitivity for cardiovascular risk stratification in hypertensives. Vnitr Lek 2010; 56(6): 607-12.
[PMID: 20681474]
[28]
Okada Y, Galbreath MM, Shibata S, et al. Relationship between sympathetic baroreflex sensitivity and arterial stiffness in elderly men and women. Hypertension 2012; 59(1): 98-104.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.176560] [PMID: 22106403]
[29]
Dutra SGV, Pereira APM, Tezini GCSV, Mazon JH, Martins-Pinge MC, Souza HCD. Cardiac autonomic modulation is determined by gender and is independent of aerobic physical capacity in healthy subjects. PLoS One 2013; 8(10): e77092.
[http://dx.doi.org/10.1371/journal.pone.0077092] [PMID: 24098577]
[30]
Facioli TP, Gastaldi AC, Dutra SGV, et al. The blood pressure variability and baroreflex sensitivity in healthy participants are not determined by sex or cardiorespiratory fitness. Blood Press Monit 2018; 23(5): 260-70.
[http://dx.doi.org/10.1097/MBP.0000000000000338] [PMID: 29994926]
[31]
Balke B, Ware RW. An experimental study of physical fitness of Air Force personnel. U S Armed Forces Med J 1959; 10(6): 675-88.
[PMID: 13659732]
[32]
Tezini GCSV, Dias DPM, Souza HCD. Aerobic physical training has little effect on cardiovascular autonomic control in aging rats subjected to early menopause. Exp Gerontol 2013; 48(2): 147-53.
[http://dx.doi.org/10.1016/j.exger.2012.11.009] [PMID: 23201548]
[33]
Maida KD, Gastaldi AC, de Paula Facioli T, de Araújo JE, de Souza HCD, De Souza HC. Physical training associated with Enalapril but not to Losartan, results in better cardiovascular autonomic effects. Auton Neurosci 2017; 203: 33-40.
[http://dx.doi.org/10.1016/j.autneu.2016.12.002] [PMID: 28043809]
[34]
Di Rienzo M, Parati G, Castiglioni P, Tordi R, Mancia G, Pedotti A. Baroreflex effectiveness index: An additional measure of baroreflex control of heart rate in daily life. Am J Physiol Regul Integr Comp Physiol 2001; 280(3): R744-51.
[http://dx.doi.org/10.1152/ajpregu.2001.280.3.R744] [PMID: 11171653]
[35]
Smyth HS, Sleight P, Pickering GW, Pickering GW. Reflex regulation of arterial pressure during sleep in man. A quantitative method of assessing baroreflex sensitivity. Circ Res 1969; 24(1): 109-21.
[http://dx.doi.org/10.1161/01.RES.24.1.109] [PMID: 4303309]
[36]
Bristow JD, Honour AJ, Pickering GW, Sleight P, Smyth HS, Smyth HS. Diminished baroreflex sensitivity in high blood pressure. Circulation 1969; 39(1): 48-54.
[http://dx.doi.org/10.1161/01.CIR.39.1.48] [PMID: 4302539]
[37]
Cushman DW, Cheung HS, Sabo EF, Ondetti MA. Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids. Biochemistry 1977; 16(25): 5484-91.
[http://dx.doi.org/10.1021/bi00644a014] [PMID: 200262]
[38]
Ferrari R, Fox K. Insight into the mode of action of ACE inhibition in coronary artery disease: the ultimate ‘EUROPA’ story. Drugs 2009; 69(3): 265-77.
[http://dx.doi.org/10.2165/00003495-200969030-00003] [PMID: 19275271]
[39]
Vijayaraghavan K, Deedwania P. Renin-angiotensin-aldosterone blockade for cardiovascular disease prevention. Cardiol Clin 2011; 29(1): 137-56.
[http://dx.doi.org/10.1016/j.ccl.2010.11.003] [PMID: 21257105]
[40]
Koba S, Xing J, Sinoway LI, Li J. Bradykinin receptor blockade reduces sympathetic nerve response to muscle contraction in rats with ischemic heart failure. Am J Physiol Heart Circ Physiol 2010; 298(5): H1438-44.
[http://dx.doi.org/10.1152/ajpheart.00558.2009] [PMID: 20207818]
[41]
Gottlieb SS, Dickstein K, Fleck E, et al. Hemodynamic and neurohormonal effects of the angiotensin II antagonist losartan in patients with congestive heart failure. Circulation 1993; 88(4): 1602-9.
[http://dx.doi.org/10.1161/01.CIR.88.4.1602] [PMID: 8403307]
[42]
Dimitrova A, Todorova M, Bianov K, Halachev N, Dineva S, Elenkova A. Treatment of moderate or severe arterial hypertension with losartan. Folia Med 1998; 40(3B) (Suppl. 3): 43-5.
[PMID: 10205992]
[43]
Williams B. Drug discovery in renin-angiotensin system intervention: Past and future. Ther Adv Cardiovasc Dis 2016; 10(3): 118-25.
[http://dx.doi.org/10.1177/1753944716642680] [PMID: 27126389]
[44]
Culman J, von Heyer C, Piepenburg B, Rascher W, Unger T. Effects of systemic treatment with irbesartan and losartan on central responses to angiotensin II in conscious, normotensive rats. Eur J Pharmacol 1999; 367(2-3): 255-65.
[http://dx.doi.org/10.1016/S0014-2999(98)00983-2] [PMID: 10079000]
[45]
Peterson RC, Dunlap ME, Angiotensin II. Angiotensin II receptor blockers in the treatment of heart failure. Congest Heart Fail 2002; 8(5): 246-256, 256.
[http://dx.doi.org/10.1111/j.1527-5299.2000.01156.x] [PMID: 12368586]
[46]
Miura S, Karnik SS, Saku K. Review: Angiotensin II type 1 receptor blockers: Class effects versus molecular effects. J Renin Angiotensin Aldosterone Syst 2011; 12(1): 1-7.
[http://dx.doi.org/10.1177/1470320310370852] [PMID: 20603272]
[47]
Inaba S, Iwai M, Furuno M, et al. Temporary treatment with AT1 receptor blocker, valsartan, from early stage of hypertension prevented vascular remodeling. Am J Hypertens 2011; 24(5): 550-6.
[http://dx.doi.org/10.1038/ajh.2011.6] [PMID: 21293390]
[48]
Santos CF, Caprio MAV, Oliveira EB, et al. Functional role, cellular source, and tissue distribution of rat elastase-2, an angiotensin II-forming enzyme. Am J Physiol Heart Circ Physiol 2003; 285(2): H775-83.
[http://dx.doi.org/10.1152/ajpheart.00818.2002] [PMID: 12714330]
[49]
Becari C, Teixeira FR, Oliveira EB, Salgado MCO. Angiotensin-converting enzyme inhibition augments the expression of rat elastase-2, an angiotensin II-forming enzyme. Am J Physiol Heart Circ Physiol 2011; 301(2): H565-70.
[http://dx.doi.org/10.1152/ajpheart.00534.2010] [PMID: 21602471]
[50]
Kirimura K, Takai S, Jin D, et al. Role of chymase-dependent angiotensin II formation in regulating blood pressure in spontaneously hypertensive rats. Hypertens Res 2005; 28(5): 457-64.
[http://dx.doi.org/10.1291/hypres.28.457] [PMID: 16156510]
[51]
Paula CA, Sousa MV, Salgado MCO, Oliveira EB. Purification and substrate specificity of an angiotensin converting elastase-2 from the rat mesenteric arterial bed perfusate. Biochim Biophys Acta Protein Struct Mol Enzymol 1998; 1388(1): 227-38.
[http://dx.doi.org/10.1016/S0167-4838(98)00186-1] [PMID: 9774738]
[52]
Shen W, Zhang X, Zhao G, Wolin MS, Sessa W, Hintze TH. Nitric oxide production and NO synthase gene expression contribute to vascular regulation during exercise. Med Sci Sports Exerc 1995; 27(8): 1125-34.
[http://dx.doi.org/10.1249/00005768-199508000-00005] [PMID: 7476056]
[53]
Vanhoutte PM, Shimokawa H, Tang EHC, Feletou M. Endothelial dysfunction and vascular disease. Acta Physiol 2009; 196(2): 193-222.
[http://dx.doi.org/10.1111/j.1748-1716.2009.01964.x] [PMID: 19220204]
[54]
Duncker DJ, Bache RJ. Regulation of coronary blood flow during exercise. Physiol Rev 2008; 88(3): 1009-86.
[http://dx.doi.org/10.1152/physrev.00045.2006] [PMID: 18626066]
[55]
Souza HCD, Ballejo G, Salgado MCO, Dias Da Silva VJ, Salgado HC. Cardiac sympathetic overactivity and decreased baroreflex sensitivity in l -NAME hypertensive rats. Am J Physiol Heart Circ Physiol 2001; 280(2): H844-50.
[http://dx.doi.org/10.1152/ajpheart.2001.280.2.H844] [PMID: 11158985]
[56]
Elayan HH, Kennedy BP, Ziegler MG. L-NAME raises systolic blood pressure in the pithed rat by a direct adrenal epinephrine releasing action. Life Sci 2002; 70(21): 2481-91.
[http://dx.doi.org/10.1016/S0024-3205(02)01520-5] [PMID: 12173412]
[57]
Mizuno Y, Jacob RF, Mason RP. Effects of calcium channel and renin-angiotensin system blockade on intravascular and neurohormonal mechanisms of hypertensive vascular disease. Am J Hypertens 2008; 21(10): 1076-85.
[http://dx.doi.org/10.1038/ajh.2008.258] [PMID: 18756260]
[58]
Kramer JM, Plowey ED, Beatty JA, Little HR, Waldrop TG. Hypothalamus, hypertension, and exercise. Brain Res Bull 2000; 53(1): 77-85.
[http://dx.doi.org/10.1016/S0361-9230(00)00311-7] [PMID: 11033211]
[59]
Zheng H, Li YF, Cornish KG, Zucker IH, Patel KP. Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure. Am J Physiol Heart Circ Physiol 2005; 288(5): H2332-41.
[http://dx.doi.org/10.1152/ajpheart.00473.2004] [PMID: 15653768]
[60]
de Abreu SB, Lenhard A, Mehanna A, et al. Role of paraventricular nucleus in exercise training-induced autonomic modulation in conscious rats. Auton Neurosci 2009; 148(1-2): 28-35.
[http://dx.doi.org/10.1016/j.autneu.2009.02.007] [PMID: 19297253]
[61]
Michelini LC, Stern JE. Exercise‐induced neuronal plasticity in central autonomic networks: Role in cardiovascular control. Exp Physiol 2009; 94(9): 947-60.
[http://dx.doi.org/10.1113/expphysiol.2009.047449] [PMID: 19617267]
[62]
Mastelari RB, de Souza HCD, Lenhard A, de Aguiar Corrêa FM, Martins-Pinge MC. Nitric oxide inhibition in paraventricular nucleus on cardiovascular and autonomic modulation after exercise training in unanesthetized rats. Brain Res 2011; 1375: 68-76.
[http://dx.doi.org/10.1016/j.brainres.2010.12.049] [PMID: 21172321]
[63]
Barbosa Neto O, Abate DTRS, Marocolo Júnior M, et al. Exercise training improves cardiovascular autonomic activity and attenuates renal damage in spontaneously hypertensive rats. J Sports Sci Med 2013; 12(1): 52-9.
[PMID: 24149725]
[64]
Masson GS, Nair AR, Silva Soares PP, Michelini LC, Francis J. Aerobic training normalizes autonomic dysfunction, HMGB1 content, microglia activation and inflammation in hypothalamic paraventricular nucleus of SHR. Am J Physiol Heart Circ Physiol 2015; 309(7): H1115-22.
[http://dx.doi.org/10.1152/ajpheart.00349.2015] [PMID: 26254332]
[65]
de la Cruz F, Geisler M, Schumann A, et al. Central autonomic network alterations in male endurance athletes. Sci Rep 2022; 12(1): 16743.
[http://dx.doi.org/10.1038/s41598-022-20064-3] [PMID: 36202877]

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