Geisa C.S.V. Tezini

Heart rate and arterial pressure variability in the experimental renovascular hypertension model in rats

This study was conducted in one kidney, one clip (1K1C) Goldblatt hypertensive rats to evaluate vascular and cardiac autonomic control using different approaches: 1) evaluation of the autonomic modulation of heart rate (HR) and systolic arterial pressure (SAP) by means of autoregressive power spectral analysis 2) assessment of the cardiac baroreflex sensitivity; and 3) double blockade with methylatropine and propranolol. The 1K1C group developed hypertension and tachycardia. The 1K1C group also presented reduction in variance as well as in LF (0.23+/-0.1 vs. 1.32+/-0.2 ms2) and HF (6.6+/-0.49 vs. 15.1+/-0.61 ms2) oscillations of pulse interval. Autoregressive spectral analysis of SAP showed that 1K1C rats had an increase in variance and LF band (13.3+/-2.7 vs. 7.4+/-1.01 mmHg2) in comparison with the sham group. The baroreflex gain was attenuated in the hypertensive 1K1C (-1.83+/-0.05 bpm/mmHg) rats in comparison with normotensive sham (-3.23+/-0.06 bpm/mmHg) rats. The autonomic blockade caused an increase in the intrinsic HR and sympathetic predominance on the basal HR of 1K1C rats. Overall, these data indicate that the tachycardia observed in the 1K1C group may be attributed to intrinsic cardiac mechanisms (increased intrinsic heart rate) and to a shift in the sympathovagal balance towards cardiac sympathetic over-activity and vagal suppression associated to depressed baroreflex sensitivity. Finally, the increase in the LF components of SAP also suggests an increase in sympathetic activity to peripheral vessels.

Cardiac Autonomic Modulation Is Determined by Gender and Is Independent of Aerobic Physical Capacity in Healthy Subjects

Background Aerobic physical capacity plays an important role in reducing morbidity and mortality rates in subjects with cardiovascular diseases. This action is often related to an improvement in the autonomic modulation of heart rate variability (HRV). However, controversies remain regarding the effects of physical training on cardiac autonomic control in healthy subjects. Therefore, our objective was to investigate whether aerobic capacity interferes with the autonomic modulation of HRV and whether gender differences exist. Methods Healthy men and women (N=96) were divided into groups according to aerobic capacity: low (VO2: 22-38 ml/kg-1 min-1), moderate (VO2: 38-48 ml/kg-1 min-1) and high (VO2 >48 ml/kg-1 min-1.) We evaluated the hemodynamic parameters and body composition. The autonomic modulation of HRV was investigated using spectral analysis. This procedure decomposes the heart rate oscillatory signal into frequency bands: low frequency (LF=0.04-0.15Hz) is mainly related to sympathetic modulation, and high frequency (HF=0.15-0.5Hz) corresponds to vagal modulation. Results Aerobic capacity, regardless of gender, determined lower values of body fat percentage, blood pressure and heart rate. In turn, the spectral analysis of HRV showed that this parameter did not differ when aerobic capacity was considered. However, when the genders were compared, women had lower LF values and higher HF values than the respective groups of men. Conclusion The results suggest that aerobic physical capacity does not interfere with HRV modulation; however, the cardiac modulatory balance differs between genders and is characterized by a greater influence of the autonomic vagal component in women and by the sympathetic component in men.

The effect of aerobic physical training on cardiac autonomic control of rats submitted to ovariectomy.

Objective: To investigate the effect of aerobic physical training on cardiovascular autonomic control in ovariectomized rats using different approaches. Design: Female Wistar rats were divided into four groups: sedentary sham rats (group SSR), trained sham rats (group TSR), sedentary ovariectomized rats (group SOR), and trained ovariectomized rats (group TOR). Animals from the trained groups were submitted to a physical training protocol (swimming) for 12 weeks. Results: Pharmacological evaluation showed that animals from group TSR had an increase in their cardiac vagal tonus compared with the animals from groups SSR and SOR. The analysis of heart rate variability (HRV) showed that groups TSR and SOR had fewer low-frequency oscillations (0.20-0.75 Hz) compared with groups SSR and TOR. When groups TSR and SOR were compared, the former was found to have fewer oscillations. With regard to high-frequency oscillations (0.75-2.5 Hz), group SSR had a reduction compared with the other groups, whereas group TSR had the greatest oscillation compared with groups SOR and TOR, with all values expressed in normalized units. Analysis of HRV was performed after pharmacological blockade, and low-frequency oscillations were found to be predominantly sympathetic in sedentary animals, whereas there was no predominance in trained animals. Conclusion: Ovariectomy did not change the tonic autonomic control of the heart and, in addition, reduced the participation of sympathetic component in cardiac modulation. Physical training, on the other hand, increased the participation of parasympathetic modulation on the HRV, including ovariectomized rats.

Aerobic physical training has little effect on cardiovascular autonomic control in aging rats subjected to early menopause

We investigated and compared the effects of physiological menopause (PM) and early menopause (EM) and the adaptations promoted by physical training on the cardiovascular autonomic control of aged rats. Female Wistar rats (N=72) were assigned to 3 groups: control (22 weeks old rats, undergoing sham surgery in the 10th week of life), PM (82 weeks old rats, undergoing sham surgery in the 10th week of life) and EM (82 weeks old rats, undergoing ovariectomy in the 10th week of life). In each group, half of the rats were subjected to swimming training over a period of 10 weeks. Sedentary PM and EM groups had higher basal mean arterial pressure (MAP) and heart rate (HR) and lower intrinsic HR compared to the sedentary control group. Physical training reduced MAP in PM group. All trained groups had lower basal HR; however, only control and PM-trained groups showed decreased intrinsic HR. The assessment of cardiac autonomic balance showed that PM and EM sedentary groups exhibited sympathetic predominance compared to control group. After physical training, only EM group presented sympathetic predominance. HR variability (pulse interval) was similar among all sedentary groups. However, control and PM-trained groups showed lower power in low frequency band (LF; 0.2-0.75 Hz) and higher power in high frequency band (HF; 0.75-3.0 Hz). The analysis of systolic arterial pressure variability revealed that PM and EM sedentary groups had higher LF power. However, PM group showed lower LF power following physical training. Finally, PM and EM groups had a reduction in spontaneous baroreflex sensitivity, that was attenuated by physical training. The overall results suggest that PM or EM promotes similar negative effects on MAP, HR and cardiovascular autonomic control. However, unlike the PM group, physical training was not able to mitigate all negative effects of EM on cardiovascular autonomic control.

Comparison of the effects of aerobic and resistance training on cardiac autonomic adaptations in ovariectomized rats

We have compared the effects of two types of physical training on the cardiac autonomic control in ovariectomized and sham-operated rats according to different approaches: double autonomic blockade (DAB) with methylatropine and propranolol; baroreflex sensibility (BRS) and spectral analysis of heart rate variability (HRV). Wistar female rats (±250g) were divided into two groups: sham-operated and ovariectomized. Each group was subdivided into three subgroups: sedentary rats, rats submitted to aerobic trained and rats submitted to resistance training. Ovariectomy did not change arterial pressure, basal heart rate (HR), DAB and BRS responses, but interfered with HRV by reducing the low-frequency oscillations (LF=0.20-0.75Hz) in relation to sedentary sham-operated rats. The DAB showed that both types of training promoted an increase in the predominance of vagal tonus in sham-operated rats, but HR variations due to methylatropine were decreased in the resistance trained rats compared to sedentary rats. Evaluation of BRS showed that resistance training for sham-operated and ovariectomized rats reduced the tachycardic responses in relation to aerobic training. Evaluation of HRV in trained rats showed that aerobic training reduced LF oscillations in sham-operated rats, whereas resistance training had a contrary effect. In the ovariectomized rats, aerobic training increased high frequency oscillations (HF=0.75-2.5Hz), whereas resistance training produced no effect. In sham-operated rats, both types of training increased the vagal autonomic tonus, but resistance training reduced HF oscillations and BRS as well. In turn, both types of training had similar results in ovariectomized rats, except for HRV, as aerobic training promoted an increase in HF oscillations.

Ageing is the main determinant of haemodynamics and autonomic cardiac changes observed in post-menopausal female rats

The aim of this study was to evaluate and compare the effects of early and physiological menopause on cardiac autonomic parameters in aged female rats. To this end, female Wistar rats (22 and 82 weeks old, N=96) were divided into 4 groups: Young Sham-operated Rats, Aged Sham-operated Rats, Young Ovariectomised (OVX) Rats, and Aged OVX Rats. Young Sham-operated and OVX rats were used as controls. The cardiac autonomic parameters were investigated using different approaches: 1) pharmacological evaluation of the autonomic tonus with methylatropine and propranolol; 2) isolated cardiac contractility with β-adrenergic agonists; and 3) quantification of the mRNA and protein level expression of cardiac β-adrenergic receptors. Among the groups of aged female rats, both the Sham-operated and OVX rats showed higher basal mean arterial pressure and heart rate (HR) values compared to their respective young counterparts. The aged groups also showed a predominance of the sympathetic autonomic component in the determination of HR, whereas the young rats showed a vagal predominance. An assessment of cardiac contractility showed that aged Sham-operated and OVX rats had lower contractile responses following the administration of dobutamine compared to their respective young counterparts. In addition, the aged groups showed higher mRNA and protein expression levels of the β1-adrenergic receptors. In conclusion, our results show that haemodynamic alterations and impairment of the autonomic parameters were similar between the groups of rats subjected to early and physiological menopause. Moreover, these results seem to be due to the ageing process and not ovarian hormone deprivation.

Autonomic Cardiovascular Damage during Post-menopause: the Role of Physical Training

Menopause is part of the aging process and is characterized by the natural cessation of menstruation; during this time, the production of ovarian hormones, especially estrogen, is sharply reduced. This reduction can cause symptoms and disorders that affect most women and can interfere with their quality of life. Women are also more susceptible to cardiovascular diseases during this period, considering that these ovarian hormones would be associated with a protective effect on the cardiovascular system, by acting at various levels, contributing to the body homeostasis. Among several effects on the cardiovascular system, the ovarian hormones seem to play an important role in the autonomic control of heart rate and blood pressure. A reduction in ovarian hormones causes an autonomic imbalance and increases the risk of cardiovascular diseases. In fact, this increased risk is justified by the key role the autonomic nervous system plays in all cardiac regulatory mechanisms, exerting a tonic and reflexive influence on the main variables of the cardiovascular system. The autonomic system controls various cardiovascular parameters, such as the modulation of heart rate and blood pressure, myocardial contractility and venous capacitance, directly participating in the regulation of cardiac output. Over the years, the standard treatment for menopause symptoms and disorders has been hormone replacement therapy (HRT). However, many studies have indicated the risks of HRT, which justify the need for new non-pharmacological therapies. To this end, physical training, mainly aerobic, has been applied with excellent results on the cardiovascular autonomic nervous system, as it reduces the risk of cardiac diseases and improves the survival rate with direct beneficial effects on the quality of life of these women during the aging process.

Cardiac acetylcholine inhibits ventricular remodeling and dysfunction under pathologic conditions.

Autonomic dysfunction is a characteristic of cardiac disease and decreased vagal activity is observed in heart failure. Rodent cardiomyocytes produce de novo ACh, which is critical in maintaining cardiac homeostasis. We report that this nonneuronal cholinergic system is also found in human cardiomyocytes, which expressed choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT). Furthermore, VAChT expression was increased 3‐ and 1.5‐fold at the mRNA and protein level, respectively, in ventricular tissue from patients with heart failure, suggesting increased ACh secretion in disease. We used mice with genetic deletion of cardiomyocyte‐specific VAChT or ChAT and mice overexpressing VAChT to test the functional significance of cholinergic signaling. Mice deficient for VAChT displayed an 8% decrease in fractional shortening and 13% decrease in ejection fraction compared with angiotensin II (Ang II)‐treated control animals, suggesting enhanced ventricular dysfunction and pathologic remodeling in response to Ang II. Similar results were observed in ChAT‐deficient mice. Conversely, no decline in ventricular function was observed in Ang II‐treated VAChT overexpressors. Furthermore, the fibrotic area was significantly greater (P < 0.05) in Ang II‐treated VAChT‐deficient mice (3.61 ± 0.64%) compared with wild‐type animals (2.24 ± 0.11 %). In contrast, VAChT overexpressing mice did not display an increase in collagen deposition. Our results provide new insight into cholinergic regulation of cardiac function, suggesting that a compensatory increase in cardiomyocyte VAChT levels may help offset cardiac remodeling in heart failure.—Roy, A., Dakroub, M., Tezini, G. C. S. V., Liu, Y., Guatimosim, S., Feng, Q., Salgado, H. C., Prado, V. F., Prado, M. A. M., Gros, R. Cardiac acetylcholine inhibits ventricular remodeling and dysfunction under pathologic conditions. FASEB J. 30, 688‐701 (2016). www.fasebj.org

Aerobic physical training increases contractile response and reduces cardiac fibrosis in rats subjected to early ovarian hormone deprivation

We investigated the effects of early ovarian hormone deprivation on the heart and the role of physical training in this condition using different approaches: cardiac autonomic tone, contractility, morphology and function, and cardiac fibrosis. Female Wistar rats (n = 48) were assigned into two groups: ovariectomized (Ovx; 10-wk-old) and control rats (Sham; 10-wk-old). Each group was further divided into two subgroups, sedentary and trained (aerobic training by swimming for 10 wk). The sedentary groups showed similar cardiac autonomic tone values; however, only the Sham group had an increase in vagal participation for the determination of the basal heart rate after physical training. The contractile responses to cardiac β-agonists of the sedentary groups were similar, including an increased response to a β1-agonist (dobutamine) observed after physical training. The Ovx sedentary group presented changes in cardiac morphology, which resulted in decreases in the ejection fraction, fractional shortening, and cardiac index compared with the Sham sedentary group. Physical training did little to alter these findings. Moreover, histology analysis showed a significant increase in cardiac fibrosis in the sedentary Ovx group, which was not observed in the trained Ovx group. We conclude that early ovarian hormone deprivation in rats impairs autonomic control, cardiac morphology, and cardiac function and increases cardiac fibrosis; however, it does not affect the contractility induced by dobutamine and salbutamol. Furthermore, this model of physical training prevented an increase in fibrosis and promoted an increase in the cardiac contractile response but had little effect on cardiac autonomic control or morphological and functional parameters.

Autonomic cardiocirculatory control in mice with reduced expression of the vesicular acetylcholine transporter

In cardiovascular diseases, sympathetic tone has been comprehensively studied, whereas parasympathetic tone has received minor attention. The vesicular ACh transporter (VAChT) knockdown homozygous (VAChT KD(HOM)) mouse is a useful model for examining the cardiocirculatory sympathovagal balance. Therefore, we investigated whether cholinergic dysfunction caused by reduced VAChT expression could adversely impact hemodynamic parameter [arterial pressure (AP) and heart rate (HR)] daily oscillation, baroreflex sensitivity, hemodynamic variability, sympathovagal balance, and cardiovascular reactivity to restraint stress. Wild-type and VAChT KD(HOM) mice were anesthetized for telemetry transmitter implantation, and APs and HRs were recorded 10 days after surgical recovery. Changes in HR elicited by methylatropine and propranolol provided the indexes of sympathovagal tone. Cardiovascular reactivity in response to a restraint test was examined 24 h after continuous recordings of AP and HR. VAChT KD(HOM) mice exhibited reduced parasympathetic and elevated sympathetic tone. Daily oscillations of AP and HR as well as AP variability were similar between groups. Nevertheless, HR variability, patterns with two dissimilar variations from symbolic analysis, and baroreflex sensitivity were reduced in VAChT KD(HOM) mice. The change in mean AP due to restraint stress was greater in VAChT KD(HOM) mice, whereas the tachycardic response was not. These findings demonstrate that the cholinergic dysfunction present in the VAChT KD(HOM) mouse did not adversely impact basal hemodynamic parameters but promoted autonomic imbalance, an attenuation of baroreflex sensitivity, and a greater pressure response to restraint stress. These results provide a framework for understanding how autonomic imbalance impacts cardiovascular function.