This research topic is dedicated to the celebration of 20 years of the Brazilian Symposium
on Cardiovascular Physiology. In 1996 groups from the School of Medicine of Ribeirao
Preto, University of Sao Paulo (FMRP-USP) and from the Federal University of Sao Paulo
(UNIFESP) joined together to discuss cardiovascular physiology. In subsequent editions
of the meeting, the participation of other groups from all over the country has grown
and acquired the status of a national symposium. The participants now agree that the
symposium should be itinerant and that the chair group is responsible for its organization.
In 2016, we proudly reached the 20th edition of the Brazilian Symposium on Cardiovascular
Physiology. It is certainly a memorable date and a great opportunity to share the
accomplishments of Brazilian groups in the field of cardiovascular physiology.
The groups devoted to investigate cardiovascular physiology in Brazil descended, in
a direct or indirect manner, from the Argentinian physiologist and Nobel Prize winner
Bernardo Houssay. One of his disciples, Miguel Covian, was invited to be the chair
of the Department of Physiology in the School of Medicine of Ribeirao Preto when it
was funded in the 1950's. At the same time, the physicians at Federal University of
Rio Grande do Sul started a collaborative work with Bernardo Houssay's and Braun Menendez's
groups. That historical perspective is presented in this issue in the article by Vasquez.
In his paper, he also shares the contributions of Professor Eduardo M. Krieger to
the development of cardiovascular physiology in Brazil.
The etiology of cardiovascular and metabolic diseases reveals the involvement of different
genetic, environmental, nutritional and behavioral aspects. In this issue, Costa-Silva
et al. discuss the role of maternal diet on the development of cardiometabolic diseases.
The authors point out that epigenetic alterations can be, at least in part, responsible
for the increased risk of developing cardiometabolic problems. The authors discuss
in detail the manner in which maternal protein undernutrition or overnutrition during
the perinatal period can increase the risk of cardiovascular and metabolic diseases.
It is important to highlight that the success of the experimental design for investigating
cardiovascular physiology depends on the availability of suitable experimental models.
In this context, Crestani reviews the effects of acute and chronic emotional stress
in cardiovascular function. The author focused on the cardiovascular responses observed
in different animal models of emotional stress. Considering the impact of stress in
the cardiovascular system in humans, this is certainly a promising area of research.
The influence of the autonomic nervous system in cardiovascular function is remarkable.
Thus, different research groups in Brazil are devoted to investigating such influence
in health and disease. In the present issue, Accorsi-Mendonça et al. present a historical
retrospective on the characteristics of rostral ventrolateral medulla (RVLM) presympathetic
neurons and discuss the concept that those cells work as pacemakers for the generation
of the sympathetic activity. Interestingly, physical activity can modulate central
areas involved in autonomic control of the cardiovascular system. In this context,
Raquel et al. show that swimming modulates nitric oxide (NO) availability and glutamatergic
neurotransmission in the RVLM, contributing to a decrease in sympathetic activity
and an increase in baroreflex control of blood pressure (BP). This provides insight
and support to the idea that physical activity should be included when treating hypertensive
patients.
Pharmacological modulation of the autonomic nervous system is an important target
to treat cardiovascular diseases (CVD). Alternative experimental approaches in this
field include the search for new natural and synthetic compounds. In this regard,
Pinto et al. observed that bombesin, a peptide isolated from frog skin, increases
blood pressure and renal sympathetic nerve activity (RSNA) when administered into
the RVLM of normotensive and spontaneously hypertensive rats (SHR). In addition, Silva
et al. show that ivabradine reduced resting heart rate and blood pressure, with no
effects on cardiovascular reflexes or RSNA.
Other important group of neurons involved in autonomic cardiovascular control are
present in the paraventricular nucleus of the hypothalamus (PVN). This region possesses
reciprocal communications with the nucleus tractus solitarii (NTS) and synapses with
both the RVLM itself and the subfornical organ (SFO), which receives information from
directly from the blood stream since it lacks a blood brain barrier. In this context,
De Melo et al. hypothesize that the decrease in ovarian hormones during menopause
blunts oxytocin expression and signaling in pre-autonomic PVN neurons, leading to
baroreflex impairment, autonomic imbalance and arterial hypertension. This reinforces
clinical findings that women are more prone to develop CVD after menopause than men
of the same age and provides experimental data to further support hormonal reposition
therapies.
Considering that an increase in blood pressure variability (BPV) is an indicative
of poor prognosis in cardiovascular outcomes, Freitas et al. demonstrate that increased
BPV prior to the onset of chronic kidney disease can reduce renal blood flow, increase
renal vascular resistance and increase uraemia and glomerulosclerosis, exacerbating
renal dysfunction. In this scenario, the authors suggest that increased BPV may be
considered as a marker for target-organ damage.
Recently, the gut microbiota has gained attention as it can be involved in the onset
of diverse pathological states, including the development of CVD. In this context,
de Brito-Alves et al. show evidence, from both experimental and clinical approaches,
that the use of polyphenols and probiotics reduces blood pressure and improves cardiovascular
function. In agreement with this, Klippel et al. present an experimental study in
which the administration of kefir (a probiotic composed by different bacteria such
as Lactobacillus kefiranofaciens, Lactobacillus kefir, and Candida kefir) to SHR resulted
in the amelioration of vagal and sympathetic imbalance, improvement of baroreflex
sensitivity and a reduction in blood pressure. Taken together, these reports emphasize
the potential of probiotics as adjuvants on CVD treatment.
Despite the fundamental role played by the central nervous system (CNS) in cardiovascular
control, the peripheral control of blood flow to target organs in response to specific
organ demands presents an important role in BP homeostasis. This is particularly evident
during sepsis and septic shock, when a massive vasodilation causes a remarkable reduction
in blood pressure, with a high mortality rate. During this state, there is also a
vascular hyporesponsivity to vasoconstrictors, limiting therapeutic options. Thus,
Pernomian et al. used an experimental model of sepsis to evaluate the participation
of C-type natriuretic peptide on this response. The authors suggest that this peptide
is involved in hyporeactivity to vasoconstrictors in aorta, revealing a novel potential
target for septic shock.
In the present issue, Costa et al. provide a relevant review on the vascular effects
of neuronal nitric oxide synthase (nNOS). It is important to highlight that, although
endothelial NOS (eNOS) is considered the main NOS isoform in vessels, nNOS is an important
source of both NO and hydrogen peroxide (H2O2), two endothelium-dependent vasodilators.
Imbalances in nNOS expression and/or activity have been described in arterial hypertension
and atherosclerosis, corroborating the idea that this isoform is particularly relevant
for proper vessel function. Nitric oxide signaling can be modulated by physical activity
not only in the CNS as previously discussed but also in the periphery. In this context,
Macedo et al. evaluated the participation of NO in vascular tone adjustments in response
to low-intensity resistance training. They observed increased expression of eNOS and
nNOS, culminating in an improvement of vascular function, increase in baroreflex sensitivity
and reduction in blood pressure.
Additionally, a further guardian of vascular homeostasis is perivascular adipose tissue
(PVAT), which can secrete vasoactive substances. In this context, Victorio et al.
comparatively evaluated the effects of PVAT from abdominal and thoracic aorta. The
authors observed functional regional differences along the aorta, with a greater production
of vasodilators in thoracic vs. abdominal PVAT.
Despite the efforts of diverse research groups in Brazil and abroad, CVD still is
the leading cause of death worldwide. The efficient function of the cardiovascular
system depends to a large degree on good cardiac function, which may be impaired after
myocardial infarction (MI), for example. In this issue, Santana et al. compare two
different techniques to induce MI in rats. Patterns of gene expression were seen to
differ between the two methods. This study certainly contributes to the standardization
of suitable experimental models that will allow new approaches to prevent and treat
MI. For instance, Manchini et al. used low-level laser therapy to improve left ventricular
systolic function. Although the results are promising, the beneficial effects seem
to be transient and long-term studies are needed. Heart failure is commonly observed
after MI and this compromises not only the function of the heart per se but also leads
to damage in target organs. It was observed by Arruda-Junior et al. that rats with
heart failure presented impaired renal function (fluid retention, reduction in glomerular
filtration rate, increase in protein excretion), which was preserved by the inhibition
of dipeptidyl peptidase IV. de Melo et al. provide us with another example of beneficial
outcomes from physical exercise. The authors evaluated the effects of exercise training
in a model of right ventricular remodeling and found that it attenuated myocardial
remodeling and improved right ventricular function.
Different strategies to deal with CVD often come from the discovery of new physiological
pathways. In this context, Xu et al. reviewed the role played by ADAM17 (A disintegrin
A metalloprotease 17) in the cardiovascular system as well as in CNS areas involved
in cardiovascular control. Although it is a very promising target molecule, the diversity
of its substrates (this enzyme is involved with more than 70 different substrates)
including inflammatory substances, have slowed the progression of translational studies.
As highlighted here, based on the quality of the different studies presented, the
initiative of creating the Brazilian Symposium on Cardiovascular Physiology 20 years
ago has contributed enormously to the development of research on cardiovascular physiology
in Brazil. The country now holds more than 20 different research groups established
from the north to the south of the country producing worldwide recognized science.
Most laboratories are well-equipped with cutting-edge technology allowing in-deep
investigations into cardiovascular phenomena. The main limitations currently faced
by Brazilian researchers are the strict rules governing the importation of research
goods (such as chemicals, reagents, live animals, viruses for gene transfer and general
lab equipment) and the uneven distribution of research funding across the country.
In conclusion, we would like to thank very much all the Brazilian research groups
who attended to the 20th Brazilian Symposium on Cardiovascular Physiology and the
reviewers who generously agreed to review the manuscripts presented in this issue.
Author contributions
CB and VB participated in all stages during the elaboration of this manuscript. Authors
read and approved the final version.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial
or financial relationships that could be construed as a potential conflict of interest.