Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Amlodipine and enalapril promote distinct effects on cardiovascular autonomic control in spontaneously hypertensive rats: the role of aerobic physical training Karina D. Maida, Suenimeire Vieira, Ada C. Gastaldi, Vanessa B. Bezerra, Joa ˜ o E. De Araujo, and Hugo C.D. de Souza Background: We compared the autonomic and hemodynamic cardiovascular effects of amlodipine and enalapril treatment associated with an aerobic physical training program on spontaneously hypertensive rats. Methods: Eighteen-week-old (n ¼ 48) spontaneously hypertensive rats were assigned to one of two groups: sedentary (n ¼ 24) and trained (n ¼ 24) through a 10-week swimming training program. Each group was subdivided into three groups (n ¼ 8): control (vehicle group), amlodipine (amlodipine group; 10 mg/kg per day) and enalapril (enalapril group; 10 mg/kg per day) (both for 10 weeks). We cannulated the femoral artery and vein of all animals for recording arterial pressure and injecting drugs, respectively. Autonomic assessment was performed by double blockade with propranolol and atropine, analysis of heart rate variability (HRV), systolic arterial pressure variability and baroflex sensitivity. Results: Arterial pressure reduction was more prominent in the sedentary and trained enalapril groups. Amlodipine sedentary group presented important autonomic adjustments characterized by a predominance of vagal tone in cardiac autonomic balance, increased HRV associated with sympathetic autonomic modulation reduction and increased vagal autonomic modulation, and increased baroflex sensitivity. All findings were not potentialized by physical training. In turn, the enalapril trained group, but not its sedentary counterpart, also had vagal tone prevalence in cardiac autonomic balance, increased HRV, increased baroflex sensitivity and decreased low-frequency band in systolic arterial pressure variability. Conclusion: Amlodipine was more effective in promoting beneficial autonomic cardiovascular adaptations in sedentary animals. In contrast, enalapril achieved better autonomic results only when combined with aerobic physical training. Keywords: amlodipine, cardiovascular autonomic control, enalapril, hypertension, physical training, spontaneously hypertensive rats Abbreviations: ACE, angiotensin-converting enzyme; AP, arterial pressure; bpm, beats per minute; BRS, baroreflex sensitivity; DAP, diastolic arterial pressure; EF, ejection fraction; FFT, fast Fourier transform; HF, high frequency; HR, heart rate; HRV, heart rate variability; iHR, intrinsic heart rate; LF, low frequency; LVEDD, left ventricular end- diastolic diameter; LVEDV, left ventricular end-diastolic volume; LVESD, left ventricular end-systolic diameter; LVESV, left ventricular end-systolic volume; MAP, mean arterial pressure; mmHg, millimeters of mercury; ms, milliseconds; nu, normalized units; PI, pulse interval; PSD, power spectral density; RRi, R-R interval; SAP, systolic arterial pressure; SAPV, systolic arterial pressure variability; SHR, spontaneously hypertensive rat; VLF, very low frequency INTRODUCTION S ystemic arterial hypertension is often accompanied by damage to cardiovascular autonomic control [1–3]. The condition is characterized by cardiac autonomic imbalance caused by greater influence of the sympathetic autonomic component and/or a reduction of the vagal autonomic component [1–3]. A decrease in bar- oreflex sensitivity (BRS) and impairment of the autonomic modulation of heart rate variability (HRV) and systolic arterial pressure variability (SAPV) are often identified [1–3]. These autonomic alterations, if not reversed, can lead to the evolution and aggravation of hypertension, often accompanied by hemodynamic loss that can result in early heart failure [1,4]. Therefore, numerous interventions have been recom- mended to effectively treat hypertension. The most com- mon includes a pharmacological approach using different classes of antihypertensive drugs. Amlodipine, a calcium channel blocker, and enalapril, an inhibitor of angiotensin- converting enzyme (ACE), are among the most widely used Journal of Hypertension 2016, 34:2383–2392 Exercise Physiology Laboratory, Ribeira ˜ o Preto Medical School, University of Sa ˜ o Paulo, Ribeira ˜ o Preto, Sa ˜ o Paulo, Brazil Correspondence to Hugo C.D. de Souza, PhD, Ribeira ˜ o Preto Medical School, University of Sa ˜ o Paulo, Exercise Physiology Laboratory, Av. Bandeirantes, 3900, Vila Monte Alegre, Ribeira ˜ o Preto 14049-900, SP, Brazil. Tel: +55 16 3315 4416; fax: +55 16 3315 4413; e-mail: hugocds@fmrp.usp.br Received 8 October 2015 Revised 25 June 2016 Accepted 10 August 2016 J Hypertens 34:2383–2392 Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/HJH.0000000000001112 Journal of Hypertension www.jhypertension.com 2383 Original Article