Physiological and Transcriptomic Changes in the Hypothalamic-Neurohypophysial System after 24 h of Furosemide-Induced Sodium Depletion.

BACKGROUND/AIMS: Furosemide is a loop diuretic widely used in clinical practice for the treatment of oedema and hypertension. The aim of this study was to determine physiological and molecular changes in the hypothalamic-neurohypophysial system as a consequence of furosemide-induced sodium depletion. METHODS: Male rats were sodium depleted by acute furosemide injection (10 and 30 mg/kg) followed by access to low sodium diet and distilled water for 24 h. The renal and behavioural consequences were evaluated, while blood and brains were collected to evaluate the neuroendocrine and gene expression responses. RESULTS: Furosemide treatment acutely increases urinary sodium and water excretion. After 24 h, water and food intake were reduced, while plasma angiotensin II and corticosterone were increased. After hypertonic saline presentation, sodium-depleted rats showed higher preference for salt. Interrogation using RNA sequencing revealed the expression of 94 genes significantly altered in the hypothalamic paraventricular nucleus (PVN) of sodium-depleted rats (31 upregulated and 63 downregulated). Out of 9 genes chosen, 5 were validated by quantitative PCR in the PVN (upregulated: Ephx2, Ndnf and Vwf; downregulated: Caprin2 and Opn3). The same genes were also assessed in the supraoptic nucleus (SON, upregulated: Tnnt1, Mis18a, Nr1d1 and Dbp; downregulated: Caprin2 and Opn3). As a result of these plastic transcriptome changes, vasopressin expression was decreased in PVN and SON, whilst vasopressin and oxytocin levels were reduced in plasma. CONCLUSIONS: We thus have identified novel genes that might regulate vasopressin gene expression in the hypothalamus controlling the magnocellular neurons secretory response to body sodium depletion and consequently hypotonic stress.

Early ovarian hormone deprivation increases cardiac contractility in old female rats-Role of physical training.

OBJECTIVES: We investigated the effects of early ovarian hormones deprivation on morphology and cardiac function and the effects of aerobic training on these parameters, in old rats. METHODS: Female Wistar rats (N = 48) were divided into two groups, at 10 weeks of life: early ovarian hormones deprivation by ovariectomy (OVX; N = 24) and sham (SHAM; N = 24). Between weeks 62 and 82, 12 animals of each group underwent aerobic training (OVX-T and SHAM-T, N = 12). At the end of week 82, all were evaluated by echocardiography, cardiac function (Langendorff technique) and cardiac ß-adrenergic receptor expression quantification. RESULTS: Echocardiography showed slight changes in morphology between OVX and SHAM groups. OVX group (Δ = 101 ±â€¯4.7 mmHg) showed higher values for maximal left intraventricular pressure in response to dobutamine, when compared to SHAM group (Δ = 55 ±â€¯11.8 mmHg). Both OVX-T (Δ = 70 ±â€¯4.0 mmHg) and SHAM-T (Δ = 22 ±â€¯6.6 mmHg) groups showed a reduction in this response. While, ß-adrenergic receptor expression was not different between the untrained groups, SHAM-T (0.23 ±â€¯0.02 AU) and OVX-T (0.29 ±â€¯0.01 AU), showed decreased expression of these receptors. CONCLUSION: Early ovarian hormones deprivation associated with aging, promotes discrete changes in cardiac morphology and increasing cardiac contractility. Aerobic training decreases ß-adrenergic receptors expression, influencing the cardiac contractility.

The blood pressure variability and baroreflex sensitivity in healthy participants are not determined by sex or cardiorespiratory fitness.

BACKGROUND: Heart rate (HR) and blood pressure (BP) autonomic modulation and baroreflex sensitivity (BRS) are important indexes of cardiovascular homeostasis. However, methodological errors are often observed, such as joint analysis of men and women. Another important aspect is that we still do not know whether cardiorespiratory fitness influences these autonomic parameters in healthy individuals. OBJECTIVES: This study aimed to investigate whether sex can affect BRS, autonomic modulation of HR and BP variabilities (HRV and BPV, respectively), as well as the influence of cardiorespiratory fitness on these autonomic parameters. METHODS: Healthy men and women (N=120) were assigned to groups according to the peak oxygen consumption (VO2 peak) obtained in the cardiorespiratory test: low cardiorespiratory fitness (VO2 peak: 22-38 ml/kg/min), moderate cardiorespiratory fitness (VO2 peak: 38-48 ml/kg/min), and high cardiorespiratory fitness (VO2 peak>48 ml/kg/min). HRV and BPV evaluations were performed for all groups in the frequency domain by spectral analysis. Spontaneous BRS was assessed using the sequence method. RESULTS: Women presented lower BP values compared with men. HR did not differ between sexes, but showed an inverse relationship with cardiorespiratory performance. The HRV analysis showed greater sympathetic modulation for men and greater vagal modulation for women. Men and women presented similar results for systolic BPV and BRS, and cardiorespiratory performance did not influence any of the autonomic parameters evaluated. CONCLUSION: Cardiorespiratory fitness does not interfere with HRV and BPV autonomic modulation or BRS. However, the cardiac modulatory balance differs between sexes, with a greater influence of the autonomic vagal component in women and the sympathetic component in men.

Physical training promotes similar effects to the blockade of angiotensin-converting enzyme on the cardiac morphology and function in old female rats subjected to premature ovarian failure.

We investigated the effects of angiotensin-converting enzyme (ACE) inhibition and aerobic physical training on the heart of old female rats (82-wk-old) submitted to premature ovarian failure (10-wk.-old). We used different approaches: morphology and function by echocardiography, reactivity of the coronary bed and left ventricular contractibility (Langendorff Technique). Female Wistar ovariectomized (OVX) rats (n=42) were assigned to one of four groups: OVX, vehicle treated only; OVX-EM, Enalapril Maleate only (EM, 10mg·kg-1·d-1); OVX-T, aerobic trained only; and OVX-EMT, treated with Enalapril Maleate and aerobic trained. Both Enalapril Maleate treatment and aerobic training were done in the last 20weeks of the experimental protocol. When compared to the OVX group, the OVX-EM group showed lower values of wall thickness and left ventricular (LV) mass, lower values of coronary bed reactivity and reduced maximum response of LV contractility to dobutamine, while the OVX-T group showed lower values of LV wall thickness, increase in end-systolic volume, reduced maximum response of LV contractility to dobutamine, and left intraventricular pressure due to increased flow. The combination of treatments (EM and aerobic physical training) did not promote additional important effects on the parameters evaluated. Our results suggest similar beneficial effects of physical training and EM treatment on the morphology and cardiac function in old female rats submitted to premature ovarian failure. Although the causes of these benefits are still unknown, both treatments have promoted a decrease in cardiac contractility, and the reduced ß1-adrenergic sensitivity suggests that both treatments may attenuate the sympathetic effect on the heart.

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 ß-agonists of the sedentary groups were similar, including an increased response to a ß1-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.

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.

Physical exercise improves cardiac autonomic modulation in hypertensive patients independently of angiotensin-converting enzyme inhibitor treatment.

We investigated the influence of angiotensin-converting enzyme inhibitor (ACEi) treatment and physical exercise on arterial pressure (AP) and heart rate variability (HRV) in volunteer patients with hypertension. A total of 54 sedentary volunteers were divided into three groups: normotensive (NT Group), hypertensive (HT Group) and HT volunteers treated with ACEi (ACEi Group). All volunteers underwent an aerobic physical-training protocol for 15 weeks. HRV was investigated using a spectral analysis of a time series of R-R interval (RRi) that was obtained in a supine position and during a tilt test. Physical training promoted a significant reduction in the mean arterial pressure of the HT group (113±3 vs. 106±1 mm Hg) and the ACEi group (104±2 vs. 98±2 mm Hg). Spectral analysis of RRi in the supine position before physical training demonstrated that the NT and ACEi groups had similar values at low frequency (LF; 0.04-0.15 Hz) and high frequency (HF; 0.15-0.5 Hz) oscillations. The HT group had an increase in LF oscillations in absolute and normalized units and a decrease in HF oscillations in normalized units compared with the other groups. The HT group had the lowest responses to the tilt test during LF oscillations in normalized units. Physical training improved the autonomic modulation of the heart rate in the supine position only in the HT group. Physical training promoted a similar increase in autonomic modulation responses in the tilt test in all groups. Our findings show that aerobic physical training improves cardiac autonomic modulation in HT volunteers independently of ACEi treatment.