Chapter 5

Hypertension and Exercise Training: Evidence

from Clinical Studies

Ivana C. Moraes-Silva, Cristiano Teixeira Mostarda,

Antonio Carlos Silva-­Filho, and Maria Claudia Irigoyen

Abstract  Hypertension is a worldwide prevalent disease, mostly manifested as its

primary ethiology, characterized by a chronic, multifactorial, asymptomatic, and
usually incurable state. It is estimated that more than one billion of the world popu-
lation is hypertensive. Also, hypertension is the main cause of the two most frequent
causes of death worldwide: myocardial infarction and stroke. Due to the necessity
of the cardiovascular system to manage chronically increased levels of blood pres-
sure, hypertension causes severe alterations in multiple organs, as the heart, vessels,
kidneys, eyes and brain, thus increasing the risk of health complications. The heart
is the main target organ and suffers several adaptations to compensate the increased
blood pressure levels; nevertheless, long-term adaptations without proper control
are extremely harmful to cardiovascular health. On the other hand, hypertension is
a modifiable risk factor and its adequate control is highly dependent on lifestyle.
Pharmacological treatment is of great success when adherence is high. Several
classes of antihypertensive drugs are prescribed and can effectively maintain blood
pressure within acceptable levels. However, non-pharmacological methods, as diet
and exercise training, can not only optimize the treatment but also prevent or post-
pone hypertension development as well as its complications, acting as important
complements to the ideal control of elevated blood pressure, and bringing together
benefits beyond blood pressure decrease, as a general health status improvement
and increased quality of life. There is consistent evidence that regular exercise train-
ing promotes several benefits when properly prescribed and practised, acting as
“medicine” for dozens of chronic diseases. The effects of exercise training in blood
pressure levels and in its mechanisms of control are of clinical relevance and effi-
cacy. This chapter will describe the classical and recent results on the beneficial

I.C. Moraes-Silva (*) • M.C. Irigoyen

Laboratory of Experimental Hypertension, Heart Institute (InCor), University of São Paulo
Medical School, São Paulo, SP, Brazil
e-mail: [email protected]
C.T. Mostarda • A.C. Silva-Filho
Department of Physical Education, Federal University of Maranhão (UFMA),
São Luís, MA, Brazil

© Springer Nature Singapore Pte Ltd. 2017 65

J. Xiao (ed.), Exercise for Cardiovascular Disease Prevention and Treatment,
Advances in Experimental Medicine and Biology 1000,
DOI 10.1007/978-981-10-4304-8_5
66 I.C. Moraes-Silva et al.

effects of different modalities of exercise training in the cardiovascular system of

human primary hypertension, focusing on the mechanisms influenced by exercise
training which help to decrease blood pressure and improve the cardiovascular
system.

Keywords  Hypertension • Exercise training • Blood pressure • Cardiovascular

system

1  Pathophysiology of Primary Hypertension

Essentially, arterial pressure is the result of the interaction between cardiac output
and peripheral resistance, and its maintenance within ideal levels is pivotal to the
organism, as it guarantees the adequate tissue perfusion in every situation. For this
reason, short-term and long-term mechanisms take part in this dynamic process to
regulate blood pressure levels in accordance with the hemodynamic demand.
Figure 5.1 depicts the main mechanisms related to blood pressure control.
Hypertension is installed when there is an imbalance of these mechanisms, either
increasing pro-hypertensive factors and/or reducing depressor factors [4]. It occurs
in response to the interaction between internal (mostly non-modifiable) and external
(mostly modifiable) elements which may favour this imbalance.
Due to the complexity and multisystem nature of blood pressure control, it is not
possible to determine only one mechanism which is responsible for primary hyper-
tension onset and maintenance. Renal mechanisms of blood pressure regulation
proposed by Guyton decades ago are still updated [5, 6]. Not less important, cardio-
vascular autonomic dysfunction, characterized mainly by sympathetic overactivity,
is a major player in the hypertensive disease [7]. More recently, it was reported that
this autonomic dysfunction can intensify inflammatory responses, thus contributing
to accelerate pathologic processes involved in cardiovascular disease, including
hypertension [8]. Also important to mention, vascular abnormalities represented by
endothelial dysfunction, enhanced oxidative stress, and vascular remodelling has
gained support to be the cause rather than the consequence of hypertension [9].
These vascular abnormalities are amplified by the interactions with other altered
mechanisms involved in blood pressure regulation.
As seen in Fig.  5.1, there are internal and external conditions which are well
known as potential risk factors for hypertension development. Fortunately, external
risk factors can be modified by lifestyle changes. In this sense, exercise training act
as a powerful alternative to complement pharmacological and dietetic interventions
in the treatment of hypertension by improving most of the mechanisms involved in
blood pressure control, thus contributing to blood pressure decrease.
5  Hypertension and Exercise Training: Evidence from Clinical Studies 67

EXERCISE TRAINING

Modifiable risk factors BLOOD PRESSURE CONTROL MECHANISMS

increased salt intake
insulin resistance neurogenic hormonal/peptidic endothelial renal
overweight autonomic nervous renin-angiotensin- nitric oxide fluid volume
sedentarism system aldosterone system endothelin sodium retention
stress baroreflex vasopressin
chemoreflex catecholamines
Non-modifiable risk factors cardiopulmonary insulin
reflex kinin-kallikrein
genetics system
age
gender
race

HYPERTENSION =

Fig. 5.1  Factors influencing mechanisms of blood pressure control: several mechanisms play to
adjust cardiac output and vascular peripheral resistance to keep blood pressure within ideal levels.
The presence of risk factors favours the imbalance of blood pressure control mechanisms, which
determines the development of primary hypertension. Due to its multifactorial nature, it is not pos-
sible to identify which mechanism is responsible for primary hypertension establishment. Exercise
training is able to modify some of the risk factors and by improving most of the mechanisms
related to blood pressure control, can reduce blood pressure, and consequently reduce the cardio-
vascular risk in hypertensive individuals

The importance of blood pressure decrease in hypertension is not only to assure

the adequate physiological status, but also to preserve the cardiovascular structure.
The heart adjusts the cardiac output according to the metabolic demand. In face of
high levels of blood pressure, the first attempt is to increase cardiac output in order
to accommodate this hemodynamic overload; however, this augment works only in
the acute phase and not when the stimulus persists. Therefore, the continuous hemo-
dynamic overload triggers pathological hypertrophic and remodelling responses of
the vascular (which explains the sustained increase vascular peripheral resistance in
hypertension), and cardiac tissues. At first, these responses contribute to normalize
cardiac performance; however, the complexity and progressiveness of cardiac
hypertrophy classify this adaptation as a risk factor for hypertensive-associated dis-
ease/events, and as predictor of mortality [10]. At long term, pathological left ven-
tricular hypertrophy (LVH) compromises cardiac function.
Decreasing left ventricular mass significantly contributes to the reduction of car-
diovascular risk [11]. Once more, exercise training can be a good partner on it.
68 I.C. Moraes-Silva et al.

2  Anaerobic Exercise Training

Anaerobic exercise, by a biochemical concept, is an exercise in which the main

source of energy for force and work production comes from energetic pathways that
are not dependent of oxygen. Those exercises have a rapid duration, mainly because
of the velocity of the work demand (which cannot be achieved by oxygen perfusion
speed), but also demands lots of energy and produces force and work in elevated
levels.
Classic examples of anaerobic exercises are the 100 m running, 50 m swimming,
100  m with hurdles, and the majority of short-term track and field sports at the
Olympics. Nevertheless, even common movements in the daily life like seating,
standing, jumping, squatting, putting an object in a shelf and all short-term life
activities are also possible due to anaerobic energy production.
Another classic example of short-term exercises is the resistance training (RT),
or strength training. By means of convention, the authors adopted the term RT as a
synonym of the other examples in this chapter.
RT is one of the most used anaerobic exercise interventions in cardiac prevention
and rehabilitation not only because of the energetic benefits per se, but also for other
morphophysiological benefits in the skeletal muscle, bones, and the cardiovascular
system [12, 13].
In hypertension, RT has been used as a resource for its treatment and comorbidi-
ties attenuation, reducing the peripheral vascular resistance, and thus, the systemic
blood pressure [12, 14]. This reduction can be due to the elevated number of metab-
olites present in the skeletal muscle during and after the exercise session [15]. These
metabolites like H+, ADP, lactate, CO2, among others, are vasodilators, and when in
high concentrations, can elicit a powerful reduction in the local blood pressure [15].
An increasing number of studies have been showing the chronic beneficial effect
of RT in the treatment of hypertension, with significant drops in both systolic and
diastolic pressure, decreased sympathetic tone, reduced peripheral vascular resis-
tance, and also decreased risk for other life-threatening cardiovascular events, as
myocardial infarction and heart failure [16–20].
Historically, RT has been seldom prescribed as an alternative for hypertension
treatment mainly due to the absence of data regarding real effects in the blood pres-
sure, being neglected by the recommendation of aerobic exercises. However, a
recent meta-analysis has shown that RT has a significant contribution in the process
of blood pressure lowering, mainly by reductions in the diastolic blood pressure,
which is representative of the peripheral vascular resistance [21]. Moreover, RT also
contributes to net blood pressure changes, with reductions around −3.87 mmHg for
systolic pressure and −3.6 mmHg for diastolic pressure [19]. Although small, those
blood pressure reductions are related with decreased risk of developing several
hypertension-associated diseases, as coronary heart disease (decrease of 5%) and
stroke (decrease of 8%). In addition, a decrease in all-cause mortality by 4% is also
observed [19, 22].
5  Hypertension and Exercise Training: Evidence from Clinical Studies 69

RT can elicit important changes in the regulation of general circulation, mainly

by adaptations of the autonomic reflexes (i.e. baroreflex, metaboreflex, mechanore-
flex, chemoreflex and etc.). Changes in the blood flow of the active muscle during
RT alter the venous return, resulting in a higher amount of blood returning to the
right atria, activating the heart stretch reflex, resulting in the activation of Frank-­
Starling mechanism, thus increasing cardiac output and blood pressure. Changes in
baroreflex sensitivity caused by chronic RT have been widely reported in the last
years [23–25].
During the RT, baroreflex is almost completely abolished by the overactivation
of other local reflexes, such as metabo-, chemo- and mechanoreflexes [26]. Among
those reflexes, the chemoreflex is known to cause the major contribution to the
attenuation of baroreflex activity during exercise, mainly by its function of control-
ling the levels of metabolites in the circulation (O2, CO2, H+, ADP etc.) [24, 26].
The rise in blood pressure during exercise driven by the chemoreflex coincide
with the decreases in O2 presence and accumulation of lactate and H+ [26]. This
chemoreflex response is also one of the main pathways for post-exercise hypoten-
sion, the fall in the blood pressure levels below the resting values after exercise [26].
Another interesting category of anaerobic exercise that has been extensively
investigated is the isometric exercise. Isometric exercises consist in exercises where
muscle length and joint angle does not change while the muscle maintain a resis-
tance against gravity, like holding a dumbbell in front of the face for a certain
amount of time. Surprisingly, this exercise has been showing incredible benefits in
reducing blood pressure, with values around −10.9 mmHg of reduction for systolic
and −6.9 for diastolic components [21].
A recent meta-analysis demonstrated that isometric exercise can be beneficial in
blood pressure reduction only in male adults over 45 years of age, in a low-intensity
training regimen, three times weekly at 30% of maximal voluntary contraction, for
more than 8 weeks [27]. In this study, hypertensive individuals showed a decrease
of 5.91 mmHg in mean arterial pressure.
Another recent study showed that one single bout of low-intensity handgrip exer-
cise (4 series of 2-min sustained handgrip contractions at 30% of maximal voluntary
contraction) significantly reduced systolic blood pressure, with a tendency to reduce
diastolic pressure, in daily life activities of pre- and stage 1 hypertensive men [28].
Some limitations to recommend isometric exercises to hypertensive patients
have to be addressed. Firstly, the hypotensive effects of isometric exercise have been
mostly investigated acutely. Secondly, the hypotensive effects do not seem to be
long lasting. Finally, the number of bouts and time of execution, as well as which
modality of isometric contraction should be executed to produce hypotensive effects
are not well defined.
Although isometric exercises have a great potential of adherence, due to its sim-
plicity and efficiency, and can produce meaningful blood pressure reductions, fur-
ther investigations should be made in order to safely include isometric exercise in
the exercise training programmes of hypertensive individuals.
As cited before in this chapter, not only blood pressure decrease but also the
protection of the cardiac organ is an endpoint for hypertension therapy. Regarding
70 I.C. Moraes-Silva et al.

LVH, there is no clinical evidence that any modality of RT is able to improve this
parameter in hypertensive patients.

2.1  Recommendations for Resistance Training Prescription

As any intervention in the hypertensive patient, the exercise program should con-
sider some safety issues as well. The most important and relevant ones will be
addressed here.
Regarding hypertensive individuals, it is very important to avoid sudden increases
in blood pressure, which can cause the rupture of pre-established aneurisms in cere-
bral blood vessels, causing haemorrhage that can lead to disability or death.
Therefore, avoiding elevated workloads or excessive short intervals that creates
elevated fatigue is strongly recommended for hypertensive patients when practising
RT.
During exercise, blood pressure responds differently in each part of the move-
ment. While the concentric phase is performed (when the muscle is being con-
tracted), there is a significant rise in the blood pressure in comparison to the eccentric
phase, and even with the resting phase [29]. This increase during contraction can be
determined by the temporary obstruction of the active muscle blood flow, which
causes a rise in the systemic blood pressure; thus, in hypertensive subjects, high
workloads without proper adaptation in this phase is highly not recommended. Just
for comparison purposes, during a one maximal repetition test (1 MRT), the rise in
blood pressure can be 2–3 times higher than the regular 120/80 mmHg values, with
the highest value ever recorded in the literature around 320/250 mmHg during a 1
MRT [30].
Also, during the RT, beginners tend to execute the exercise improperly. For the
professional accompanying the hypertensive subject, it is necessary to under-
standthe possible errors that could lead to unnecessary rises in the blood pressure.
One of the most common errors in the exercise execution is the Valsalva maneuver.
This maneuver consists in the abrupt inspiration and its interruption, causing signifi-
cant rises in the thoracic pressure.
The dangerous effects of this maneuver consist in the sudden increase in thoracic
and systemic blood pressure consequently, which can cause rupture of aneurisms
and increase the risk for cardiac events. Also, the reflex response to this enormous
increase in blood pressure is also an enormous decrease in blood pressure, which
can lead to oxygen absence in the brain, resulting in faint and dizziness [29, 31].
Therefore, during the execution of the RT, normal expiration flows should be main-
tained during the concentric phase, thus avoiding the risk of the Valsalva
maneuver.
The architecture of the training program is also very important when applying
the concepts for hypertensive individuals. During the RT, the control of the blood
pressure is only possible via the aspects of the exercises. For this reason, it is crucial
5  Hypertension and Exercise Training: Evidence from Clinical Studies 71

to observe the following points when prescribing a RT for hypertensive

individuals:
• High intensity exercises are known to cause higher increases in blood pressure
than moderate exercises [32]. The control of the exercise intensity should be
carefully considerate, with preference for the moderate-intensity regimen;
• Exercises with short intervals also lead to higher increases in blood pressure.
Intervals between exercises should be long enough to reestablish blood pressure
close to the beginning levels [33, 34];
• Exercises executed to voluntary exhaustion are not recommended, because they
may cause significant increases in blood pressure [30, 32];
• Exercises that recruit great muscle groups or multiarticular exercises that recruit
many muscles are also known to cause more enhanced increases in blood pres-
sure than exercises recruiting small or less muscle groups [35].
These considerations should be taken into account mainly in the beginning of the
training program. With the progression of the patient, more intense and diverse
training regimens might be incorporated, for more sustained and significant benefits
for the patient’s health, always avoiding unnecessary risks.

3  Aerobic Exercise Training

Aerobic exercise is by definition an exercise in which the energy produced for its
maintenance occurs in the presence of oxygen. These exercises are usually of long
duration and generate great amounts of energy. Different from the anaerobic exer-
cise, it takes longer to produce the same amount of energy.
The great advantage of aerobic energy production is the efficiency of the path-
way, in which every substrate (proteins, carbohydrates and lipids) can be burned
into ATP. Also, the aerobic energy production can adequately sustain a longer work-
load without greater interruptions.
The aerobic exercises are totally dependent of the cardiopulmonary system for
exchange, transportation and removal of O2 and CO2, thus, this same system is the
main benefited from the stress and overload caused by aerobic exercises.
Aerobic exercise has been the main exercise alternative for the treatment of
hypertension due to its benefits in heart, vessels, lungs, muscles and all systems
involved in the regulation of blood pressure [12, 23]. The benefits of aerobic exer-
cises to its practitioners begins with increased cardiac output, non-pathological left
ventricular hypertrophy, better vascular compliance, diminished peripheral vascular
resistance, increased muscle oxidative capacity, among others [14, 36].
For the hypertensive patient, aerobic exercises, either performed acutely or
chronically, can positively affect the vessels, by increasing compliance (i.e. as the
capacity of the vessel to contract and relax, mainly relax); the heart, by increasing
the pumping capacity, reducing heart rate and the coronary flow pressure; the mus-
cles, that act as a powerful venous return pump; the peripheral flow, by diminishing
72 I.C. Moraes-Silva et al.

the peripheral resistance and thus the systemic pressure; the autonomic nervous
system, by adjusting the sympathovagal balance, mainly by increasing vagal activ-
ity, which is beneficial for heart protection; and many other benefits [37].
As cited earlier in this section, the muscle metabolites produced during exercise
have a robust contribution in the reduction of the local blood pressure. Interestingly,
as opposite of the local muscular response (blood pressure reduction), systemically,
the blood pressure is augmented, mainly driven by the increased sympathetic activ-
ity in the heart and the vessels. This phenomenon is called functional sympatholy-
sis, in which the abolishment (the lysis) of the systemic sympathetic activation in a
specific tissue happens by a local hypotensive factor, like metabolites and other
vasodilators (nitric oxide in the active tissue) in the skeletal muscle during the exer-
cise. This mechanism drives the blood flow to the active tissues which, due to the
vasodilation, are more susceptible to blood perfusion and oxygen exchange, facili-
tating the energy delivery during exercise. This is one of the mechanisms explaining
the drop of blood pressure after an acute aerobic exercise session, and also after
chronic exercise programmes, altogether with increased vagal activity and reduced
peripheral vascular resistance [38].
Additionally, exercise is known as a modulator of the baroreflex, as it was shown
by Laterza et al. (2007) [39]. In his study, hypertensive patients who never received
any pharmacological treatment joined a combined exercise program. Measurements
of the baroreflex were made by muscle microneurography and blood pressure
recordings simultaneously. The results showed a recovery of the baroreflex activity
to normal levels, together with significant reduction in sympathetic activity, and in
blood pressure, indicating a powerful restoration capacity of the exercise regarding
autonomic function and modulation in hypertension. Years earlier, it was demon-
strated that aerobic exercise training elicited a modest baroreflex sensitivity
improvement in mild and borderline hypertensive patients [40, 41].
Besides the positive effects in neurogenic mechanisms of blood pressure control,
aerobic exercise training also influences the vascular peripheral resistance. Vascular
remodelling is one of the compensatory adaptations to chronic increased levels of
blood pressure, and once more exercise training can positively affect it, acting in the
reverse remodelling of the vessels. Hansen et al. (2010) [42] showed that hyperten-
sive patients after 16 weeks of moderate aerobic training reduced blood pressure
accompanied by an increase in muscle capillary-fiber ratio in association with
increased expression of vascular endothelial growing factor.
Aerobic exercise causes physiological LVH, differently from the pathological
LVH caused by the increased overload. Changes in chamber size, wall thickness,
inter-septum thickness and myocyte size are remarkable in the exercising heart. In
hypertensive patients, it was observed that exercise training was associated with a
paradoxical regression of LVH or even a prevention of cardiac hypertrophy [43]. A
study conducted by Rinder et al. (2004) [44] aimed to compare the blood pressure-­
lowering capacity and reversion of the pathological LVH in hypertensive adults
taking thiazides and exercise training. Although exercise showed a more reduced
capacity of lowering blood pressure than thiazide, it reverted the pathological LVH
as much as the pharmacological treatment. Moreover, other favourable effects as
5  Hypertension and Exercise Training: Evidence from Clinical Studies 73

increased aerobic and movement capacity, and decreased insulin resistance were
achieved only with exercise training.
Another interesting study regarding cardiac structure and function after exercise
training in hypertensive should be mentioned. Andersen et al. (2014) [45] reported
that men with mild-to-moderate hypertension, evaluated by echocardiography,
importantly improved diastolic function after 3 months of football training in com-
parison with sedentary patients. After 6 months of the same training, parameters of
cardiac structure were not changed, which means that, at least, cardiac hypertrophy
was not in progress.
In elderly hypertensive patients, aerobic exercise training induced partial regres-
sion of LVH [46]. Positive repercussions of exercise training in cardiac function of
old hypertensive subjects were also reported [47]. On the contrary, despite the
reduction in blood pressure, and increased physical and strength capacities, Guirado
et al. (2012) [48] showed that a 6-month of combined exercise training (aerobic +
resistance) 3 times/week in controlled hypertensive elderly patients did not change
parameters of morphology and function by echocardiography.
Mechanisms behind exercise-induced changes in cardiac structure and function
are vastly studied in animal models, eliciting pathways of molecular and cellular
levels; however, in humans, these mechanisms are not fully studied. Even though it
is complicated to determine the influence of hypertension, exercise and pharmaco-
logical treatment to LVH and total heart function, exercise can be a strong contribu-
tor to the cardiac health improvement for the hypertensive patient.

3.1  Recommendations for Aerobic Exercise

As the majority of studies were conducted with aerobic exercise training for decades,
it is the main recommendation for the alternative or adjuvant treatment for hyperten-
sion, with a “A” level of evidence and “I” class of recommendation, according to the
American Heart Association [49]. Many studies have shown the potential benefits of
aerobic exercise, with reductions around −3.5  mmHg for systolic and diastolic
-3 mmHg [21].
Also, aerobic exercise is an excellent adjuvant treatment for hypertension due to
its safety. Aerobic exercises consist in walking, running, biking, swimming, danc-
ing, and other diverse activities that are usually very pleasant and can be executed
for longer periods.
The aerobic exercise should be prescribed based on various methods, such as
maximal heart rate (HRmax), percentual of reserve heart rate (%HRR), scales of
perceived exertion (such as the Borg scale), subjective analysis of the expiration
flow (if the subject could not talk while exercising, it is on the adequate intensity)
or, by direct measurements (VO2max).
According to the ACSM’s recommendation for exercise prescription for adults,
aerobic exercise should be practised for periods between 30–60 min of moderate to
vigorous intensity, 3–5 times a week [36]. This recommendation is also corrobo-
rated by the American Heart Association for the treatment of hypertension [49].
74 I.C. Moraes-Silva et al.

Due to its cardiovascular necessity and greater muscle recruitment, the aerobic
exercise has been demonstrated as the most significant tool for lowering blood pres-
sure, also with more substantial decreases in blood pressure and more prominent
benefits in the cardiac system than RT [21, 49].
In addition, the aerobic exercise does not affect only the cardiovascular system,
it also changes other risk factors for the development and maintenance of elevated
blood pressure, as reducing obesity and adipose tissue [50], reducing circulating
LDL levels and increasing HDL levels [51], and controlling diabetes [52].

4  Other Modalities of Exercise Training

Although aerobic training complemented by resistance exercises is the current rec-

ommendation for hypertensive individuals to benefit from exercise adaptations,
there are other modalities of exercise that can compose the training programmes for
hypertension prevention and treatment. These modalities also present improve-
ments in blood pressure profile, and contribute to the general benefits profited by
exercise trainings.
In general, exercises that promote relaxing and control of respiration, as most of
the modalities mentioned in the upcoming sections, are able to decrease blood pres-
sure due to optimized cardiovascular reflex responses and improved modulation of
the autonomic nervous system, mostly by decreasing sympathetic overactivity and
increasing the vagal component.
It is important to mention that, although there is no high level of evidence and
recommendation of the following modalities in terms of blood pressure decrease in
hypertension, all of them can be practised by hypertensive patients under the spe-
cific recommendations and avoidances already presented in this chapter as a com-
plement to aerobic training and healthy lifestyle.

4.1  Respiratory Training

Although involuntary and most of the time unnoticed, breathing is an important ele-
ment of the cardiovascular homeostasis. Characterized by the diaphragm move-
ments, the breathing pattern can be practised and optimized by respiratory trainings.
Slow and regular breathing has been associated with blood pressure reductions in
hypertensive patients.
A music-guided training to induce a slower and regular breathing pattern was
tested in controlled and uncontrolled hypertensive patients (10  min/day, for
8 weeks). The authors showed that this approach was able to decrease systolic and
diastolic blood pressure (−16.8 and −11.5 mmHg, respectively) [53]. Another study
involving controlled breathing also reported positive effects of this practise in blood
pressure levels of hypertensive patients. An acute protocol of controlled breathing at
5  Hypertension and Exercise Training: Evidence from Clinical Studies 75

6  cycles/min compared with spontaneous breathing showed that slow breathing

reduced blood pressure and improved baroreflex sensitivity [54].
As mentioned in the introduction of this section, autonomic and reflex mecha-
nisms are the main responsible determinants of blood pressure decrease after the
adoption of slower breathing patterns. Lung inflation increases when breathing
cycles are diminished; this mechanical alteration stimulates pulmonary stretch
receptors and evokes the Hering-Breuer reflex to avoid lung over-inflation. This
serves as an input to the medulla, a key region for cardiopulmonary reflexes, where
information generated by arterial baroreceptors is converged and integrated [55].
Therefore, as the reflex mechanism dictates, in face of an acute blood pressure aug-
ment and/or lung inflation, a vagal-mediated response is activated, with decreased
cardiac chronotropic and inotropic activities, and decreased vascular peripheral
resistance, inducing systemic vasodilation, and consequently reducing blood pres-
sure. As breathing cycles are continuously performed in lifetime, this mechanism is
constantly activated, thus contributing to keep blood pressure in lower levels also in
chronic evaluations.
Inspiratory muscle training (IMT) is a modality of respiratory training in which
patients breathe against a load calculated from their maximal static inspiratory pres-
sure [56]. Hypertensive patients who underwent IMT for 8 weeks at 30% of their
maximal static inspiratory pressure presented decreased levels of daytime systolic
and diastolic blood pressure (−7.9 and −5.5 mmHg, respectively) accompanied by
a decrease in sympathetic modulation and an increase in parasympathetic modula-
tion [56]. Using a similar IMT protocol, Ferreira et al. (2016) [57] demonstrated
that, similarly to aerobic training, IMT reduced sympathetic activity and improved
endothelial function in controlled hypertensive patients after 12 weeks of training.

4.2  Tai chi

Another example of exercise modality that favours slow and regular breathing train-
ing is tai chi, a low impact exercise which is commonly practised in China but has
practitioners worldwide.
A systematic review concluded that tai chi is effective in lowering blood pressure
in different populations [58]. Lo et  al. [59] corroborated this result reporting
decreases of 9.71  mmHg in systolic pressure and 1.96  in diastolic pressure, and
improvements in exercise behaviour in hypertensive tai chi practitioners after
8 weeks. Pan et al. [60] also found significant reductions in the blood pressure of
hypertensive patients and suggested that this reduction may be correlated with
increased plasma levels of vasodilatory endogenous gaseous signalling molecules
(NO, CO and H2S).
76 I.C. Moraes-Silva et al.

4.3  Yoga

This modality is based on isometric, stretching and breathing exercises, deep relax-
ation techniques and meditation. All of these elements can be beneficial to hyperten-
sive individuals, including isometric exercises, as discussed earlier in this chapter. A
systematic review of randomized trials indicated that yoga is able to decrease blood
pressure in hypertension, with a more significant decrease in systolic than in dia-
stolic pressure and increased effectiveness in pre-hypertensive patients [61]. Another
study using a sphygmomanometer before and after the yoga session encountered
reductions of 12.4 mmHg and 8.6 mmHg in systolic and diastolic blood pressures,
respectively, after 3 months of twice-a-week integrative yoga training in hyperten-
sion [62]. Although it may be an interesting alternative and complementary approach
to hypertension exercise therapy, the real effectiveness of yoga in blood pressure
levels is still inconclusive [61].

4.4  Pilates

Pilates training is a modality widely practised by people of all ages. It consists pre-
dominantly of posture and abdominal exercises which realign and strengthen mus-
cles. The huge variance of exercises and possibility of adaptations enables to work
from low to advanced levels. It is predominantly a dynamic resistance exercise,
includes isometric elements and, most of the times, controlled breathing. Usually,
pilates training integrates most of osteomuscular rehabilitation programs, although
it can also take part in high performance training programmes.
Controlled trials regarding pilates training and the cardiovascular system very
are scarce. Due to its combined nature, possible results of pilates in hypertension,
having blood pressure decrease as the endpoint, may follow the resistance training
understandings regarding the responsible mechanisms [63]; nevertheless, there is no
consensus about blood pressure decrease with pilates training. An elegant study of
Martins-Meneses et  al. [64] with controlled hypertensive menopausal women
showed significant decreases of both clinical and ambulatory blood pressure after
16 weeks of mat pilates.

5  E
 xercise Training and Pharmacological Interactions
in Hypertension

Exercise has rose as a very promising non-pharmacological tool for the treatment of
hypertension, mainly via decreases in heart rate, sympathetic activity and peripheral
vascular resistance (PVR), as reported earlier in this section. However, pharmaco-
logical treatment is almost always necessary for the adequate control of
5  Hypertension and Exercise Training: Evidence from Clinical Studies 77

hypertension. In this context, exercise acts as an adjuvant, where the patient is

exposed both to the medications and to the exercise routine.
Thus, it is important to understand the interactions between the effects of the
medications and the body’s physiological response to exercise in order to adequate
exercise prescription and recommendations. In this section the most popular classes
of antihypertensive drugs will be briefly described followed by the main interac-
tions with exercise training. Important to mention is the fact that both medicated and
non-medicated hypertensive patients can benefit from exercise training effects.

5.1  Diuretics

The diuretics are a class of medications aimed to reduce the total blood volume,
extruding Na2+ and water from the extracellular matrix to the renal circulation, thus
stimulating diuresis and decreasing blood volume, and consequently, the blood
pressure. This mechanism is usually an initial effort to control the blood pressure,
and the results are usually seen in the first weeks of usage [65, 66].
Some side-effects are the excessive extrusion of important ions like Na2+ and K+,
sometimes causing hypokalaemia and insulin resistance. The most used class of
diuretics is the tiazidic (hydrochlorotiazide and dihydrochlorotiazide) accompanied
by a hyposodic diet.
During exercise and treatment with diuretics, two aspects must be focused: (a)
the hydration status of the patient and; (b) the level of K+. Diuretics cause water loss
and may be prejudicial for the exercise performance, causing dizziness and faint;
therefore, adequate water ingestion is recommended.
Hypokalaemia is a common episode in the diuretic treatment of hypertension,
seen by the loss of liquids caused by the tiazidic medications. In addition to this, the
exercise causes rise in body temperature and increased sweating, which also
increases rates of K+ loss via sweating. In a patient already losing K+, is really
important the screening of K+ levels to assure safety while in an exercise program
for hypertension. Hypokalaemia can cause dizziness, faint and rhabdomyolysis,
thus is very important a nutritional support for K+ alongside the exercise and the
treatment with diuretics [66].

5.2  Angiotensin-Converting Enzyme Inhibitors (ACEi)

This class of anti-hypertensives act in a different setting of the blood pressure con-
trol, inhibiting the conversion of Angiotensin 1 in Angiotensin 2. The renin converts
the angiotensinogen into angiotensin 1, and the Angiotensin-converting enzyme
(ACE) converts the angiotensin 1 into angiotensin 2. The angiotensin 1 has a moder-
ate to low capacity for blood pressure increases, but, its conversion by the ACE into
78 I.C. Moraes-Silva et al.

angiotensin 2 increases strongly its ability to increase blood pressure, by augment-

ing vascular constriction, resulting in increased PVR and heart rate [67].
As a target to pharmacological reduction of blood pressure, the ACEi were devel-
oped to stop the conversion of angiotensin 1 into angiotensin 2, reverting its hyper-
tensive effects. The most common ACEi are the commercial versions of captopril
and enalapril.
To this date, no significant interaction or problem has been reported in the litera-
ture regarding the use of ACEi and exercise. Recent studies have demonstrated that
long-term use of ACEi prevents the reduction of muscle oxidative activity, which
may be beneficial for older adults, prolonging the exercise capacity [68].

5.3  Angiotensin Receptor 1 (AT1) Blockers

Another way of preventing the activity of the renin-angiotensin-aldosterone system

in not only the inhibition of the enzymes, like the ACE, but also aiming the receptor
blockade, as in the case of the blockade of the AT1 receptors. This receptor is present
in the cardiomyocytes, in the vessels and in the kidney, increasing heart rate, con-
striction and stimulating Na2+ retention, all to increase blood pressure. The blockade
of this receptors stop the hypertensive effects of angiotensin 2, resulting in signifi-
cant reductions in systemic blood pressure [69]. The most used AT1 blockers are the
commercial version of losartan and valsartan.
To this date, no interaction between exercise and use of AT1 blockers were
reported in the literature. In an experimental rat model, Leite et al. [70] found an
increased metabolic expenditure in the animals treated with AT1 blockers; however,
these findings were not found in human trials.

5.4  Central Alpha 2 Agonists

This kind of anti-hypertensives were developed focusing on the alpha 2 adrenergic

receptors present in the central nervous system, thus reducing the sympathetic activ-
ity, and consequently, the heart rate and blood pressure [71].
Those medications act as sympathomimetic, meaning that they act like the adren-
ergic neurotransmitter noradrenaline in the alpha 2 adrenergic receptors, inhibiting
adenylate cyclase activity and prompting brainstem signals for vasodilation. The
most used alpha 2 agonists are the commercial versions of clonidine, methyldopa
and guanfacine.
The relationship between exercise and alpha 2 agonists are scarce in the litera-
ture. Due to the reduction in total sympathetic activity, delays in heart rate increase
and blood pressure can be present in some cases, which may be seen with caution.
Exercise can benefit the user of clonidine by increasing the alpha 2 receptor
sensitivity.
5  Hypertension and Exercise Training: Evidence from Clinical Studies 79

5.5  Vasodilators

The vasodilators act directly in the vascular smooth muscle cells and are especially
used in the emergency treatment of high blood pressure. Such action initiates relax-
ation of the vessels, decreasing peripheral vascular resistance and, consequently,
blood pressure and afterload. However, these medications have a short and not-­
sustained effect, seen that the system rapidly resets to its hypertensive setting. The
use of vasodilators is known to cause reflex tachycardia, because of the reduction of
afterload, thus activating chambers distension reflex. This reflex activation may
cause angina pectoris and myocardial infarction in patients with coronary artery
disease. They are usually combined with other medications, like beta-blockers or
diuretics.

5.6  Calcium Channel Blockers

The calcium channel blockers are designed to specially block voltage-gated calcium
channels, avoiding the inward flux of calcium to the cell. These receptors are spread
in the cardiac muscle, but are especially present in the sinoatrial and atrioventricular
nodes, regulating the rate of contraction by the depolarization of the nodes around
them. The Ca2+ blockers interrupt the influx of calcium to the cell, especially the
L-type Ca2+ channels, avoiding the calcium entering, thus reducing the cross bridge
forming and contraction; this blockade reduces the cardiac output and thus the
blood pressure systemically [72].
Currently, two types of Ca2+ blockers are available, the dyhidropyridinic and the
non-dyhidropyridinic forms. The dyhidropyridinic are derived form a molecule
called dyhidropyridin, which reduces PVR and consequently blood pressure. The
non-dyhidropyridinic form of the Ca2+ blockers are based in a variety of other mol-
ecules, such as phenylalkylamine and benzothiazepine [67, 72].
The most used drugs to block voltage-gated calcium channels are the commer-
cial versions of amlodipine, clevidipine (dyhidropyridinic), verapamil and diltiazem
(non-dyhidropyridinic).
The use of exercise alongside the Ca2+ channel blockers are related with reduced
heart rate for the same amount of exercise of a normal individual, due to the reduc-
tion of cardiac contractility and output. These reductions end up in a discrete reduc-
tion in maximal oxygen consumption (VO2max) [73]. These changes must be taken in
consideration for the exercise prescription.
80 I.C. Moraes-Silva et al.

5.7  Beta-Blockers

Beta-blockers are pharmacological molecules designed to act and interrupt the

binding site of the adrenergic agonists noradrenaline and adrenaline, the beta adren-
ergic receptors ß1 and ß2. These receptors when activated by the adrenergic agonists,
prompt mediate intracellular response via G-protein coupling, resulting in increased
contractility of the myocyte. This increase in myocyte contractility results in
increased heart rate, cardiac output and blood pressure [74]. The blockade of the
ß-receptors interrupts the intracellular response, thus avoiding the increases in con-
tractility, and consequently the increases in heart rate and blood pressure [65].
Currently, three types of ß-blockers exist in the market, the ß-selectives, which
bind specifically the ß-adrenergic receptors ß1 and ß2 (atenolol); the non-selectives,
binding every adrenergic receptor, irrespective of classification (propanolol); and
the ones with vasodilator properties altogether with the chronotropic effects
(carvedilol) [74].
Although, in the face of the adequate physiological rationale behind the
ß-­blockers, many side-effects have been reported during the treatment, such as
bronchospasms, severe bradycardia, glucose tolerance, LDL increases, among oth-
ers [75].
Due to the chronotropic effects of ß-blockers, exercise prescription and screen-
ing should be carefully analysed. Usually, the individual exercising under ß-blocker
influence shows reduced heart rate for the same amount of exercise, affecting the
exercise monitoring through the heart rate. For the prescription, the test should be
taken under ß-blocker influence, as well as the exercise regimen, thus avoiding
biases in the monitoring.
Also, seen that the cardiac output is reduced due to the reduction in contractility,
the VO2max is also affected by the use of ß-blocker; therefore, exercise prescription
based on the VO2max is not recommended, being preferred other methods based on
the rate of perceived exertion or lactate threshold.

6  Conclusions

Exercise training is an optimal tool to treat and prevent hypertension and its associ-
ated diseases and dysfunctions. Once the exercise program is adequately prescribed
and accompanied, patients can benefit not only from blood pressure decrease and
better regulation, but also from improved quality of life and general health status.
The most well conducted, reproducible, and conclusive studies were done with
aerobic exercise training. For this reason, by now, aerobic exercises at low-to-­
moderate intensities are the first choice to safely promote beneficial effects in
hypertension and must be the most predominant modality in exercise training
programmes.
5  Hypertension and Exercise Training: Evidence from Clinical Studies 81

Despite the growing number of studies with resistance and isometric trainings in
hypertension, there are remaining controversies and factors to be elucidated.
Therefore, resistance exercises should only complement the training programmes
due to their specific effects in bones and muscles (which will also help in aerobic
training performance). Finally, adding other modalities that contribute to patient’s
adherence to a healthier lifestyle is welcomed, always respecting the specialized
recommendations.
Importantly, exercise training does not substitute pharmacological treatment, and
medications should not be stopped once exercise training begins. The ideal control
of hypertension should include adequate diet, exercise training, and pharmacologi-
cal treatment, supervised by a multidisciplinary team.

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