Scand J Med Sci Sports 2014: ••: ••–•• doi: 10.1111/sms.12280

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Post-resistance exercise hemodynamic and autonomic responses: Comparison between normotensive and hypertensive men A. C. C. Queiroz1, J. C. S. Sousa1, A. A. P. Cavalli1, N. D. Silva Jr1, L. A. R. Costa1, E. Tobaldini2, N. Montano2, G. V. Silva3, K. Ortega3, D. Mion Jr3, T. Tinucci1,3, C. L. M. Forjaz1 1

Exercise Hemodynamic Laboratory, School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil, Department of Biomedical and Clinical Sciences “L. Sacco”, Medicine and Physiopathology, L. Sacco Hospital, University of Milan, Milan, Italy, 3Hypertension Unit, General Hospital, University of São Paulo, São Paulo, Brazil Corresponding author: Andréia Cristiane Carrenho Queiroz, PhD, Exercise Hemodynamic Laboratory, School of Physical Education and Sport, University of São Paulo, Av. Prof. Mello Moraes, 65 Butantã, São Paulo, SP 05508-030, Brazil. Tel: +55 11 30918792, Fax: +55 11 38135921, E-mail: [email protected] 2

Accepted for publication 28 May 2014

To compare post-resistance exercise hypotension (PREH) and its mechanisms in normotensive and hypertensive individuals, 14 normotensives and 12 hypertensives underwent two experimental sessions: control (rest) and exercise (seven exercises, three sets, 50% of one repetition maximum). Hemodynamic and autonomic clinic measurements were taken before (Pre) and at two moments post-interventions (Post 1: between 30 and 60 min; Post 2: after 7 h). Ambulatory blood pressure (BP) was monitored for 24 h. At Post 1, exercise decreased systolic BP similarly in normotensives and hypertensives (−8 ± 2 vs −13 ± 2 mmHg, P > 0.05), whereas diastolic BP decreased more in hypertensives (−4 ± 1 vs −9 ± 1 mmHg, P < 0.05). Cardiac output and systemic vascular resistance did not

change in normotensives and hypertensives (0.0 ± 0.3 vs 0.0 ± 0.3 L/min; −1 ± 1 vs −2 ± 2 U, P > 0.05). After exercise, heart rate (+13 ± 3 vs +13 ± 2 bpm) and its variability (low- to high-frequency components ratio, 1.9 ± 0.4 vs +1.4 ± 0.3) increased whereas stroke volume (−14 ± 5 vs −11 ± 5 mL) decreased similarly in normotensives and hypertensives (all, P > 0.05). At Post 2, all variables returned to pre-intervention, and ambulatory data were similar between sessions. Thus, a session of resistance exercise promoted PREH in normotensives and hypertensives. Although this PREH was greater in hypertensives, it did not last during the ambulatory period, which limits its clinical relevance. In addition, the mechanisms of PREH were similar in hypertensives and normotensives.

Hypertension is a very prevalent chronic disease and considered one of the most important risk factors for cardiovascular disease (Chobanian et al., 2003). Aerobic exercise is recommended for the treatment of hypertensives, and nowadays resistance exercise has been added to this recommendation as an adjunct therapy (Williams et al., 2007; American College of Sports Medicine, 2010). A single session of aerobic or resistance exercise reduces blood pressure (BP) during the recovery period, which is called post-exercise hypotension. To be clinically significant, however, this BP reduction should have an important magnitude and should last for many hours after the end of the exercise (Kenney & Seals, 1993). Post-resistance exercise hypotension (PREH) has been extensively reported in normotensive subjects (Rezk et al., 2006; Moraes et al., 2007; Queiroz et al., 2009, 2013b; Teixeira et al., 2011). The magnitude of systolic/diastolic BP reductions after resistance exercise in these individuals varies from −4/−2 to −14/−4 mmHg. In regard to the duration of PREH in normotensives, most of the studies reported significant decreases for 60–90 min after the exercise, but a decrease on

post-resistance exercise ambulatory BP has not been observed (Queiroz et al., 2009). Nevertheless, studies point out that BP reduction after a resistance exercise session is greater in subjects with higher pre-exercise BP (Queiroz et al., 2009). Studies in patients with hypertension have reported reductions of systolic/diastolic BP of −12/−6 to −23/−14 mmHg (Hardy & Tucker, 1998; Melo et al., 2006; Moraes et al., 2007, 2012). These reductions may be sustained up to 10 h during ambulatory conditions (Melo et al., 2006). Together, these results suggest that PREH should be greater and last longer in hypertensives than normotensives. However, to our knowledge, no study has compared PREH magnitude and duration between these subjects after the same exercise session. Hemodynamic and autonomic determinants of PREH have been investigated in normotensives but not in hypertensives. In normotensives, BP reduction was attributed to a decrease in cardiac output (CO) promoted by a reduction in stroke volume (SV) and not accompanied by an increase in systemic vascular resistance (SVR) (Teixeira et al., 2011). The decrease in CO

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Queiroz et al. occurred despite an increase in heart rate (HR) produced by the maintenance of an elevated sympathetic modulation to the heart after the exercise (Teixeira et al., 2011), which may have been promoted by a decrease in arterial baroreflex sensitivity of HR (Queiroz et al., 2013a). Hypertension is accompanied by many cardiovascular and autonomic alterations, such as increased SVR (Ting et al., 1986), sympathetic activity (Grassi et al., 1998) and renin-angiotensin activity (Sakata et al., 2002), and decreased endothelial function (Iiyama et al., 1996) and arterial baroreflex sensitivity of HR (Grassi et al., 1998). These alterations might influence the hemodynamic and autonomic mechanisms of PREH, changing its determinants in hypertensives, which, as far as we know, has not been studied yet. Thus, the purpose of this study was to describe and compare clinic and ambulatory BP behavior after a single session of resistance exercise in normotensive and hypertensive men, investigating the hemodynamic and autonomic mechanisms involved in these responses. As anti-hypertensive medications might change hemodynamics, denying the understanding of the influence of the disease per se on the responses, the hypertensives were studied under placebo treatment. Methods Participants Twelve essential stage 1 or 2 hypertensive men without any target organ damage and 14 normotensive men matched for age and body mass index participated in this study. Before the enrolment, all of the participants signed an informed written consent form approved by the Ethics Committee of the School of Physical Education and Sport, University of São Paulo (n° 2010/05). The study was registered at the Brazilian Registry of Clinical Trials (RBR-8MX5G6). The inclusion criteria for the study were age between 30 and 60 years, non-smoker, body mass index lower than 35 kg/m2, and not physically active (i.e., does not practice any physical activity or practices at most twice a week). The exclusion criteria were presence of secondary hypertension, renal dysfunction, ventricular hypertrophy, diabetes, cardiovascular disease, musculoskeletal disease, use of drugs for hypercholesterolemia control, and systolic/diastolic BP levels while receiving placebo greater than 160/105 mmHg. Except for the last exclusion criteria, all others were assessed by preliminary evaluations conducted while patients were receiving their regular drug treatments. After preliminary evaluations, hypertensives who fulfilled the study criteria underwent a 2-week washout period with placebo before starting the experimental procedures, and during this washout period, if BP increased above 160/105 mmHg, the patients were excluded. During the study, patients’ systolic/ diastolic BP before and after the washout period were 134 ± 3/ 91 ± 2 and 134 ± 3/94 ± 1 mmHg, respectively. In addition, hypertensives also received placebo during the 4 weeks of the study. To assure hypertensives’ safety during the entire period without medication, BP was measured every week, and the subjects were excluded and medication resumed if their systolic/ diastolic BP levels were above 160/105 mmHg. For ethical reasons, hypertensives were informed that they would receive placebo during the study. However, they were not informed at which weeks of the study the placebo would be administered.

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They received masked medications (placebo or regular drugs) from the research physicians during all the study period.

Preliminary evaluation All volunteers answered an anamnesis about their health status and practice of physical activity. Afterwards, their resting auscultatory BP was measured three times after 5 min of seated rest in two visits, following the recommendations of the European Society of Hypertension (O’Brien et al., 2005). Subjects who presented systolic/diastolic BP < 130/85 mmHg were considered normotensives. Subjects who took antihypertensive medications or presented systolic/diastolic BP ≥ 140/90 mmHg were considered hypertensives. In addition, in the hypertensives, the hypertension diagnosis was checked by measuring BP again in two visits during the last week of the washout period. They only remain in the study if BP persisted at the hypertensive levels previously described. All hypertensives were clinically examined by a physician. In addition, they underwent the routine exams from the Hypertension Unit of the General Hospital that followed the Brazilian Guidelines for Hypertension (Brazilian Hypertension Society, 2010). An electrocardiogram (ECG) was also performed before and during a maximal exercise test conducted on a treadmill using a ramp protocol. Subjects were excluded from the study if they present any sign of myocardial ischemia or supraventricular and ventricular arrhythmias. In addition, VO2 was continuously assessed during the test by a metabolic cart (Medical Graphics Corporation, CPX/D, St. Paul, Minnesota, USA), and VO2 peak was determined by the maximal value achieved during effort. Afterwards, all subjects underwent two resistance exercise adaptation sessions and a one repetition maximum (1 RM) test following the Kraemer and Fry’s protocol (Kraemer & Fry, 1995). The adaptation and test were performed in seven resistance exercises: chest press, leg press, lat pull down, squat, arm curl, right leg curl, and left leg curl.

Experimental protocol During the experimental period, all subjects (normotensives and hypertensives) underwent both a control and an exercise session that were performed in a random order and with an interval of at least 48 h between them. The experimental sessions began at approximately 08:00 hours and were carried out in a climatecontrolled room (21.7 ± 0.2 °C). Subjects were asked to wear clothes appropriate for physical activity; not to ingest coffee, tea, coke, alcohol, or other central nervous system stimulants on the day of the experiments; to avoid exercise for the 48 h preceding the experimental sessions; and to maintain similar activities on the experimental days. The experimental protocol followed in each session was exactly the same for normotensives and hypertensives. In each session, subjects remained seated for 60 min before the intervention (preintervention period). Then, they moved to the exercise room where they stayed for 40 min, resting during the control session and exercising during the exercise session. Subjects did not know which intervention they were going to do until the beginning of the intervention. In the control session, subjects were positioned on the exercise machines but did not perform any exercise. In the exercise session, volunteers performed three sets of repetitions until moderate fatigue (slowing of movement) in the seven resistance exercises mentioned above. Exercises were performed with an intensity of 50% of 1 RM, and resting intervals between sets and exercises lasted 90 s. After the interventions, subjects returned to the laboratory and remained seated for 60 min (first postintervention period – Post 1). Afterwards, they had 20 min to take a shower in both experimental sessions (exercise and control), and an ambulatory BP device was attached to their non-dominant arm.

Post-resistance exercise responses Subjects left the laboratory to their daily activities and returned after 5 h. At that moment, they rested again in the seated position for another 60 min (second post-intervention period – Post 2). Afterwards, they left the laboratory again and returned the next day, 24 h after the end of the intervention. During the ambulatory periods, subjects were instructed to maintain their usual activities and to avoid physical exercise, alcohol ingestion, shower, and daytime sleep. They were also asked to report and maintain similar activities after both experimental sessions. At each 60-min measurement period (Pre-intervention, Post 1, and Post 2), ECG, respiratory activity, and beat-by-beat BP were collected for 10 min, from 30 to 40 min, for autonomic assessment. Subsequently, hemodynamic measurements (BP, CO, and HR) were taken in triplicate from 45 to 60 min, and the mean value was calculated for each period.

Measurements Auscultatory BP was measured on the dominant arm by the same trained observer in both experimental sessions using a mercury column. Two researchers performed the measurements, and the intraclass correlation coefficients between them were 0.883 and 0.889 for systolic and diastolic BP, respectively. HR was measured by ECG immediately after the BP measurement. CO was estimated by the indirect Fick method, employing the CO2 rebreathing technique (Jones et al., 1967) and a metabolic cart (Medical Graphics Corporation, CPX/D), as previously reported (Teixeira et al., 2011). SV and SVR were calculated. For autonomic evaluation, ECG, respiratory activity (Pneumotrace 2, UFI, Morro Bay, California, USA), and beat-bybeat BP (Finometer, Finapres Medical System, Amsterdam, the Netherlands) were acquired with a data acquisition system (Dataq Instruments, DI-720, Akron, Ohio, USA), with a sampling rate of 500 Hz per channel. Autoregressive spectral analysis of R-R interval variability was performed (Heart Scope II, AMPS LLC, Central Park West, New York, USA) as previously described (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996). The oscillatory components of the time series were modeled by the Levinson–Durbin recursion, and the order of the model was automatically chosen according to Akaike’s criterion. Low- (LFR-R: 0.04–0.15 Hz) and high-frequency (HFR-R: 0.15–0.4 Hz) components were expressed in normalized units (nu). The normalized values were calculated as each power component relative to the total power minus the very low-frequency component (0–0.04 Hz). The LFR-R and HFR-R components were accepted as markers of predominant cardiac sympathetic and parasympathetic modulations, respectively, and the ratio between these components was considered a marker of cardiac sympathovagal balance (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996; Montano et al., 2009). Vasomotor sympathetic modulation was considered using the analysis of the absolute value of the low-frequency component of systolic BP (LFSBP) variability (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996). Spontaneous arterial baroreflex sensitivity of HR was evaluated by the highest value of the transfer function between the R-R interval and systolic BP variabilities at the low-frequency band when the coherence between these signals was > 0.5, and the phase was negative (Robbe et al., 1987). Ambulatory data were measured every 15 min for 24 h by an oscillometric device (Spacelabs 90207, Spacelabs, Inc., Redmond, Washington, USA), and the device calibration was regularly checked (Campbell et al., 1990). Data were analyzed by the following averages: Post 1–2 (all measures taken between Post 1 and Post 2); 24 h (all measurements taken during 24 h), awake (all

measurements taken while the subject reported to be awake), and asleep (all measurements taken while subject reported to be sleeping) periods.

Statistical analysis Considering a power of 90%, an alpha error of 5%, and a standard deviation of 3 mmHg for systolic BP and 0.32 L/min for CO, the minimal sample sizes necessary to detect a difference of 4 mmHg and 0.32 L/min were calculated to be 10 and 11 subjects in each group, respectively. Data distribution was checked by Shapiro–Wilk test (IBM, SPSS, Chicago, IL, USA). Logarithm transformation was applied for non-normally distributed variables. An independent t-test was used to compare normotensive and hypertensive characteristics. In each group, absolute values measured pre- and post-interventions in both sessions were compared by a two-way analysis of variance (ANOVA) for repeated measures, establishing sessions (control and exercise) and stages (Pre, Post 1, and Post 2) as the main factors (Statistica for Windows, Statsoft, Tulsa Oklahoma, USA). To compare normotensive and hypertensive behaviors, the exercise net effect in each group was calculated using the following: Exercise net effect = (PostExercise − Pre-Exercise) − (Post-Control − Pre-Control). The net effects were compared between groups with an independent Student’s t-test. Ambulatory data were compared by a two-way ANOVA, establishing group (normotensive and hypertensive) as a between factor and session (control and exercise) as a within factor (Statistica for Windows, Statsoft). Whenever necessary, post-hoc comparisons were made by Newman–Keuls test. P ≤ 0.05 was defined as significant. Data are presented as mean ± standard error.

Results Baseline systolic, diastolic, and mean BP, as well as SVR, were significantly higher in hypertensives than normotensives (Table 1). All the other physical, hemodynamic, autonomic, and functional variables were similar between normotensives and hypertensives. The mean workloads employed for each exercise also did not differ between normotensives and hypertensives (53 ± 4 vs 52 ± 3 kg for chest press, 86 ± 7 vs 93 ± 5 kg for leg press, 40 ± 3 vs 37 ± 2 kg for lat pull down, 65 ± 6 vs 59 ± 4 kg squat, 19 ± 2 vs 16 ± 1 kg for arm curl, 20 ± 1 vs 18 ± 1 kg for right leg curl, 20 ± 1 vs 18 ± 1 kg for left leg curl, respectively, P ≥ 0.05). In the normotensive group, eight subjects began the experimental protocol with the control session and six with the exercise session. In hypertensive group, six subjects began with each session. Hemodynamic data measured in both sessions in normotensives and hypertensives are shown in Fig. 1, panels a and b, respectively. In normotensives, at Post 1, systolic, and diastolic BPs decreased after the exercise (P < 0.001 and P = 0.002, respectively). CO and SVR did not change in either of the sessions (P > 0.05). However, an individual analysis revealed that 57% of the subjects presented a reduction in CO and 43% in SVR after the exercise. SV decreased (P = 0.007) and HR increased (P = 0.002) after the exercise in these subjects.

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Queiroz et al. Table 1. Physical, hemodynamic, autonomic, and functional characteristics of the subjects

Variables

Normotensive

Hypertensive

P

N Age, years Weight, kg Height, cm Body mass index, kg/m2 Resting systolic BP, mmHg& Resting diastolic BP, mmHg& Resting mean BP, mmHg& Resting heart rate, bpm Systemic vascular resistance, U Cardiac output, L/min Stroke volume, mL ln LF/HFR-R ln LFSBP, mmHg2 BRS, ms/mmHg VO2 peak (mL/kg/min) 1 RM chest press, kg 1 RM leg press, kg 1 RM lat pull down, kg 1 RM squat, kg 1 RM arm curl, kg 1 RM right leg curl, kg 1 RM left leg curl, kg

14 44 ± 3 79.2 ± 2.8 175 ± 0 25.9 ± 1.0 113 ± 2 76 ± 2 89 ± 2 69 ± 2 18 ± 1 5.1 ± 0.3 75 ± 4 0.74 ± 0.27 2.0 ± 0.2 7.8 ± 1.0 33.6 ± 1.5 104 ± 7 171 ± 13 80 ± 5 131 ± 11 38 ± 3 41 ± 3 40 ± 2

12 50 ± 3 82.6 ± 3.1 172 ± 0 27.8 ± 0.8 134 ± 3 94 ± 1 105 ± 2 68 ± 1 21 ± 1 5.3 ± 0.3 78 ± 4 0.61 ± 0.26 2.5 ± 0.2 4.3 ± 0.7 29.4 ± 1.7 104 ± 6 187 ± 9 75 ± 3 114 ± 8 32 ± 2 36 ± 2 36 ± 2

0.181 0.426 0.221 0.176 < 0.001 < 0.001 < 0.001 0.695 0.047 0.647 0.634 0.734 0.098 0.051 0.071 0.980 0.368 0.452 0.269 0.160 0.181 0.231

All values are expressed as means ± standard error. & Values measured three times after 5 min of seated rest in two visits after 2-week washout period. 1 RM, one repetition maximum; BP, blood pressure; BRS, baroreflex sensitivity; HF, high-frequency component; LF, low-frequency component; ln, natural logarithm; SBP, systolic blood pressure; U, arbitrary unit.

Fig. 1. Systolic blood pressure (SBP), diastolic blood pressure (DBP), cardiac output (CO), systemic vascular resistance (SVR), stroke volume (SV), and heart rate (HR) measured, in the normotensives (panel a) and hypertensives (panel b), before (Pre) and after 30–60 min (Post 1) and 7 h (Post 2) of the interventions in the control (dashed line) and exercise (solid line) sessions. *Significantly different from Pre (P ≤ 0.05). #Significantly different from the control session (P ≤ 0.05).

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Post-resistance exercise responses

Fig. 2. Exercise net effect calculated for systolic blood pressure (SBP), diastolic blood pressure (DBP), cardiac output (CO), systemic vascular resistance (SVR), stroke volume (SV), heart rate (HR), total variance (TVR-R), sympathovagal balance (LF/HFR-R), high-frequency (HFR-R) and low-frequency (LFR-R) bands of R-R interval variability, low-frequency band of systolic blood pressure variability (LFSBP), and baroreflex sensitivity (BRS) at the post-intervention evaluations realized after 30–60 min (Post 1) and 7 h (Post 2) in normotensives (black bars) and hypertensives (white bars). $Significantly different from the normotensive group (P ≤ 0.05).

At Post 2, all variables were similar pre-intervention values in both sessions (P > 0.05). In hypertensives, at Post 1, systolic, and diastolic BPs decreased after the exercise (P < 0.001 and P = 0.005, respectively). CO decreased and SVR increased similarly in both control and exercise sessions (P < 0.001 and P < 0.001, respectively). Individual analysis revealed that 33% of the subjects presented a reduction in CO, 50% in SVR, and 17% in both after the exercise. SV decreased (P < 0.001) and HR (P < 0.001) increased after the exercise. At Post 2, systolic and diastolic BPs increased significantly in comparison with preintervention values in the exercise (P = 0.012 and P = 0.016, respectively) and in the control (P < 0.001 and P = 0.001, respectively) sessions, and this increase was similar between these sessions (P > 0.05). All other variables returned to pre-intervention values at Post 2 (P > 0.05). Comparisons of the exercise net effect between normotensives and hypertensives showed that the effect of exercise decreasing diastolic BP at Post 1 was greater in hypertensives than normotensives (−9 ± 1 vs −4 ± 1 mmHg, respectively, P = 0.016) (Fig. 2). For all other hemodynamic variables, the exercise net effects were similar in normotensives and hypertensives. Ambulatory systolic, diastolic, and mean BPs were higher in hypertensives than normotensives. In both groups, systolic, diastolic, and mean BPs, as well as HR,

averaged for all the periods, were similar (P > 0.05) between the control and exercise sessions (Table 2). Autonomic data observed in both sessions in normotensives and hypertensives are shown in Table 3. In both groups, normotensives and hypertensives, at Post 1, exercise decreased total variance of R-R interval (P < 0.001 and P < 0.001, respectively), HFR-R nu (P < 0.001 and P < 0.001, respectively), and arterial baroreflex sensitivity of HR (P < 0.001 and P = 0.005, respectively). LFR-R nu (P < 0.001 and P < 0.001, respectively) and LF/HFR-R (P < 0.001 and P < 0.001, respectively) increased, and LFSBP did not change after exercise (P > 0.05). At Post 2, all autonomic indexes returned to pre-intervention values (P > 0.05). The exercise net effects for all the autonomic variables were similar in normotensives and hypertensives (P > 0.05) (Fig. 2). Discussion The study was designed to describe and compare hemodynamic and autonomic responses after a single session of resistance exercise in normotensives and hypertensives. The most important findings were (a) PREH occurs in both normotensives and hypertensives; (b) the magnitude of systolic BP decrease after exercise was similar in normotensives and hypertensives, but diastolic BP reduction was greater in hypertensives; (c) in both groups, PREH was not sustained during ambulatory

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Queiroz et al. Table 2. Ambulatory blood pressure and heart rate measured in the control and in the exercise sessions in the normotensive and hypertensive subjects

Variables

Normotensives

Hypertensives

Control

Exercise

Control

Exercise

123 ± 2 117 ± 2 122 ± 2 108 ± 2

143 ± 3$ 138 ± 3$ 144 ± 3$ 125 ± 4$

145 ± 4$ 139 ± 3$ 144 ± 4$ 125 ± 3$

79 ± 2 72 ± 1 78 ± 1 63 ± 2

96 ± 3$ 91 ± 3$ 96 ± 2$ 78 ± 3$

96 ± 3$ 90 ± 2$ 95 ± 3$ 78 ± 3$

93 ± 2 87 ± 1 93 ± 1 78 ± 2

112 ± 3$ 107 ± 3$ 112 ± 3$ 93 ± 3$

113 ± 3$ 106 ± 3$ 111 ± 3$ 93 ± 3$

80 ± 3 70 ± 2 75 ± 2 63 ± 2

80 ± 3 75 ± 3 78 ± 3 66 ± 3

82 ± 3 74 ± 2 77 ± 2 67 ± 2

Systolic blood pressure, mmHg Post 1–2 124 ± 2 24 h 117 ± 2 Awake 122 ± 2 Asleep 109 ± 3 Diastolic blood pressure, mmHg Post 1–2 79 ± 2 24 h 72 ± 1 Awake 78 ± 1 Asleep 63 ± 2 Mean blood pressure, mmHg Post 1–2 94 ± 2 24 h 87 ± 1 Awake 93 ± 1 Asleep 79 ± 2 Heart rate, bpm Post 1–2 79 ± 3 24 h 71 ± 2 Awake 75 ± 3 Asleep 65 ± 3

Post 1–2 = 5-hour interval between the post-intervention measurements 1 and 2. Values = means ± standard error. $ Significantly different from the normotensive group (P ≤ 0.05).

conditions; (d) hemodynamic and autonomic mechanisms of PREH were similar in normotensives and hypertensives; and (e) in both groups, the systemic hemodynamic determinant (CO or SVR) of PREH varied among the subjects, but BP reduction was accompanied by a reduction in SV and arterial baroreflex sensitivity of HR and by the maintenance of increased HR and cardiac sympathovagal balance after the exercise stimulus. PREH magnitude observed in normotensives (−8/ −4 mmHg) was within the range reported by previous studies (−4/−2 to −14/−4 mmHg) (Rezk et al., 2006; Moraes et al., 2007; Queiroz et al., 2009, 2013b; Teixeira et al., 2011). Concerning hypertensives, we were able to find only two studies that investigated unmedicated hypertensives and both reported a greater BP reduction (−22/−8 to −23/−14 mmHg) than the current one (Moraes et al., 2007, 2012). The lower hypotensive effect obtained in the present study might be attributed to the lower BP level accepted for study participation (BP < 160/105 mmHg). It is known that PREH is related to pre-exercise BP (Queiroz et al., 2009), and the greater diastolic hypotension observed in hypertensives in comparison with normotensives reinforces this argument. In addition, a previous study with medicated hypertensives that employed the same BP inclusion criteria (Melo et al., 2006) observed a PREH similar to the one reported here (−12/ −6 mmHg).

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In normotensives and hypertensives, PREH was detected at Post 1 and was not sustained under ambulatory conditions, showing that it lasted for approximately 60 min. A previous study with unmedicated hypertensives also failed to report a decrease in ambulatory BP after a session of resistance exercise (Hardy & Tucker, 1998). However, in hypertensive women receiving captopril, PREH lasted 10 h under ambulatory condition (Melo et al., 2006). It is possible that the use of anti-hypertensive medications may maximize the magnitude and duration of PREH; this hypothesis requires further investigation. In addition, differences in gender may also influence ambulatory BP response after exercise, as hemodynamic and autonomic variables differ between men and women at rest (Huxley, 2007) and in their response to exercise (Parker et al., 2007). Nevertheless, a study with normotensives reported similar clinic PREH in men and women (Queiroz et al., 2013b). However, hypertensives may respond differently and ambulatory BP may be more sensitive to gender differences. The failure to maintain PREH under ambulatory condition limits the clinical relevance of resistance exercise for hypertension treatment (Kenney & Seals, 1993). A recent meta-analysis reported that post-aerobic exercise hypotension lasts for many hours (Cornelissen et al., 2013), which reinforces the use of resistance exercise as an adjunction to aerobic training in hypertension treatment. It is worth noting that at Post 2 (i.e., 7 h after the interventions), hypertensives but not normotensives presented an increase in BP. Because this BP increase occurred in both experimental sessions (control and exercise), it was probably due to the circadian increase in BP between 08:00 and 17:00 hours (Portaluppi & Smolensky, 2007). Hypertensives are more sensitive to circadian behaviors (Hermida et al., 2007). In addition, they are also more reactive to pressor stimuli (Kaushik et al., 2004). These aspects may explain why this increase was observed only in the hypertensive group. To our knowledge, this is the first study to investigate the mechanisms of PREH in hypertensives, and to demonstrate that they did not differ from the ones observed in normotensives. This similarity, however, was contrary to the hypothesis that hypertensives and normotensives would respond differently after resistance exercise because they present different hemodynamic and autonomic characteristics. However, in the current study, normotensives and hypertensives did not differ in almost all of the physiological parameters analyzed, except for BP and SVR, which might be explained by the hard inclusion and exclusion criteria adopted in this study to guarantee that hypertensives did not present any other alteration except for hypertension. Future study, however, should investigate these mechanisms in hypertensives with comorbidities and baseline alterations.

Post-resistance exercise responses Table 3. Autonomic data measured in the normotensive and hypertensive groups before (Pre) and after 30–60 min (Post 1) and 7 h (Post 2) of the interventions in the control and exercise sessions

Variables

Normotensives ln TVR-R, ms2 LFR-R, nu HFR-R, nu ln LF/HFR-R ln LFSBP, mmHg2 BRS, ms/mmHg Hypertensives ln TVR-R, ms2 LFR-R, nu HFR-R, nu ln LF/HF ln LFSBP, mmHg2 BRS, ms/mmHg

Control

Exercise

Pre

Post 1

Post 2

Pre

Post 1

Post 2

7.3 ± 0.1 66 ± 5 31 ± 5 0.9 ± 0.3 2.1 ± 0.3 7.9 ± 1.0

8.2 ± 0.1* 55 ± 5* 40 ± 5 0.4 ± 0.4 2.4 ± 0.2 11.5 ± 1.0*

7.3 ± 0.2 67 ± 6 30 ± 5 1.1 ± 0.4 2.2 ± 0.3 8.1 ± 1.2

7.3 ± 0.2 60 ± 6 37 ± 6 0.6 ± 0.3 1.9 ± 0.2 7.8 ± 1.1

7.0 ± 0.3# 80 ± 5*# 17 ± 4*# 2.0 ± 0.4*# 2.5 ± 0.2 6.2 ± 0.9#

7.2 ± 0.2 68 ± 5 30 ± 4 0.9 ± 0.2 2.3 ± 0.2 7.0 ± 0.8

6.6 ± 0.2 59 ± 6 36 ± 5 0.6 ± 0.3 2.4 ± 0.3 5.0 ± 0.6

7.6 ± 0.2* 59 ± 5 38 ± 5 0.5 ± 0.2 2.5 ± 0.3 8.0 ± 1.3*

6.8 ± 0.2 66 ± 5 30 ± 5 0.9 ± 0.2 2.4 ± 0.2 5.0 ± 0.6

7.0 ± 0.3 60 ± 5 34 ± 5 0.6 ± 0.2 2.6 ± 0.2# 5.6 ± 0.8

6.6 ± 0.3# 81 ± 5*# 15 ± 4*# 1.9 ± 0.3*# 3.2 ± 0.3# 4.2 ± 0.4#

6.5 ± 0.3 65 ± 5 29 ± 3 0.8 ± 0.2 2.6 ± 0.2# 4.9 ± 0.8

Values = means ± standard error. *Significantly different from the pre-intervention (P ≤ 0.05). # Significantly different from the control session (P ≤ 0.05). BRS, baroreflex sensitivity; HF, high-frequency component; LF, low-frequency component; ln, natural logarithm; nu, normalized units; SBP, systolic blood pressure; TV, total variance.

Interestingly, in both groups, part of the sample presented a decrease in CO and part of the sample demonstrated a reduction in SVR after exercise. Thus, mean data were not able to reveal a specific systemic hemodynamic determinant for PREH in either of the groups. This individualized behavior has already been reported after aerobic exercise (Forjaz et al., 2004). After resistance exercise, previous studies reported a decrease in CO in young normotensive subjects of both genders exercised to fatigue (Rezk et al., 2006; Teixeira et al., 2011). Differences in age, gender, and especially in conducting exercise to fatigue, which might maximize venous return decrease after exercise, may explain the differences in results. Nevertheless, the reason why some subjects responded with a decrease in CO and others with a decrease in SVR after the resistance submaximal exercise is unclear and should be addressed in the future using specific study designs for this question. After the exercise, SV decreased in all subjects. Mechanisms responsible for the SV decrease were out of the scope of the present study, but a decrease in pre-load seems to be a possible mechanism, as resistance exercise decreases venous return (Collins et al., 1989). This reduction has been explained by a decrease in plasma volume produced by fluid shift from plasma to interstitial space during exercise (Rotstein et al., 1998). In addition, it has been suggested that venous compliance increases after aerobic exercise (Dujic et al., 2006), which may also occur after resistance exercise. Compared with pre-exercise, HR was elevated at Post 1 in all subjects. This may reflect the unloading of the arterial baroreflex by BP reduction (Aires, 2008). However, as exercise decreased arterial baroreflex sensitivity of HR in both groups, this reflex response was

not able to abolish PREH. HR increase after a resistance exercise session has been reported to last only for several minutes in young subjects after a low-intensity exercise (Rezk et al., 2006) or for many hours after a highintensity exercise in elderly subjects (Queiroz et al., 2013a). In the present study, HR increase after a lowintensity exercise in middle-aged normotensive and hypertensive men lasted for 1 h. This increase was accompanied by an increase in LFR-R nu and LF/HF and a decrease in HFR-R nu in both groups, showing that cardiac sympathetic modulation remained elevated and parasympathetic modulation remained reduced after exercise for the first hour of recovery. This autonomic change was not maintained for a long time after the exercise, and hypertension condition did not affect autonomic responses to resistance exercise. The hemodynamic responses observed in the control session in hypertensives, a decrease in CO and an increase in SVR, might seem odd at first. These responses, however, have already been reported by others (Rezk et al., 2006; Teixeira et al., 2011) and have been attributed to the orthostatic stress imposed by the sitting position. This stress may reduce venous return, decreasing SV (Shvartz et al., 1983) and deactivating cardiopulmonary reflexes, which increases peripheral sympathetic activity, SVR, and BP. This afterload increase may contribute to SV decrease, tending to decrease CO. All of these mechanisms, however, might be opposed by baroreflex stimulation due to BP increase (Lohmeier et al., 2005; Aires, 2008). As hypertensives are more responsive to cardiopulmonary deactivation, more reactive to pressor stimuli, and have lower baroreflex sensitivity than normotensives (Mark & Mancia, 1996; Oliver et al., 2009), these differences may

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Queiroz et al. explain why SVR increased and CO decreased only in hypertensives throughout sitting time in the control session. The main new finding of the present study is that the magnitude of PREH, especially for diastolic BP, was greater in hypertensives. The mechanisms for the greater BP reduction in these subjects were not clear. However, hypertensives present higher SVR than normotensives (Ting et al., 1986), and diastolic BP is mainly influenced by SVR. Although exercise did not reduce mean SVR in hypertensives, the percentage of subjects who presented a decrease in SVR after resistance exercise was higher in hypertensives than in normotensives (50% and 43%, respectively, P = 0.0001, chi-square test). This study investigated a low-intensity resistance exercise until moderate fatigue, which is the exercise protocol recommended for hypertensives (Williams et al., 2007; American College of Sports Medicine, 2010; Brazilian Hypertension Society, 2010). It included only sedentary men and subjects without any other health problem besides essential hypertension. Thus, results are applied just to subjects and exercise protocols similar to those mentioned herein. Moreover, hypertensives were not receiving pharmacological treatment, and results may be different in medicated patients. Besides randomizing session order, in hypertensives, preintervention ln LFSBP was higher in the exercise compared with the control session; however, this difference was maintained at the post-intervention evaluations and, thus, might not have affected the results. In conclusion, in normotensive and hypertensive men, a single session of resistance exercise promoted PREH. This hypotensive effect was greater for diastolic BP in hypertensives but lasted only for a short period of time after exercise and was not sustained under ambulatory conditions. The hemodynamic and autonomic determinants PREH were similar in normotensives and hypertensives. Decreased BP after exercise was due to a decrease in CO in some subjects and a decrease in SVR in others. In addition, PREH was accompanied

by a decrease in SV and maintenance of increased HR after exercise, which is probably mediated by the maintenance of increased cardiac sympathovagal balance and by the reduction in arterial baroreflex sensitivity of HR. Perspectives First, the findings from this study showed that a single session of resistance exercise performed in accordance with the hypertension guidelines (Williams et al., 2007; American College of Sports Medicine, 2010; Brazilian Hypertension Society, 2010) produces greater PREH in hypertensive than normotensive men. However, this hypotensive effect lasted for only 1 h and was not sustained during daily activities, which limits its clinical relevance for hypertension treatment (Kenney & Seals, 1993). Thus, future studies should investigate ways to prolong this PREH, such as the use of a different exercise protocol or the association of exercise with antihypertensive medication. Second, this study showed that despite the greater hypotensive effect, the hemodynamic and autonomic adjustments observed after exercise were similar in normotensives and hypertensives. Previous studies on these mechanisms have investigated only normotensive subjects (Rezk et al., 2006; Teixeira et al., 2011; Queiroz et al., 2013a,b), and thus the present results extended the scientific knowledge about this issue by showing the mechanisms in hypertensives. Key words: Hypertension, autonomic modulation, ambulatory blood pressure, strength exercise.

Acknowledgements The authors want to acknowledge the subjects who contributed to this study. We also thank the General Hospital staff for medical care provided to the subjects. This study was financially supported by FAPESP (2009/18219-3; 2011/06689-5), CNPQ (146168/ 2011-9; 237320/2012-6), CAPES, and Pró-Reitoria de Graduação USP.

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