Trained Spontaneously Hypertensive Rats Research Articles

Effects of physical training on hypothalamic neuronal activation and expressions of vasopressin and oxytocin in SHR after running until fatigue.

To assess the influence of physical training on neuronal activation and hypothalamic expression of vasopressin and oxytocin in spontaneously hypertensive rats (SHR), untrained and trained normotensive rats and SHR were submitted to running until fatigue while internal body and tail temperatures were recorded. Hypothalamic c-Fos expression was evaluated in thermoregulatory centers such as the median preoptic nucleus (MnPO), medial preoptic nucleus (mPOA), paraventricular nucleus of the hypothalamus (PVN), and supraoptic nucleus (SON). The PVN and the SON were also investigated for vasopressin and oxytocin expressions. Although exercise training improved the workload performed by the animals, it was reduced in SHR and followed by increased internal body temperature due to tail vasodilation deficit. Physical training enhanced c-Fos expression in the MnPO, mPOA, and PVN of both strains, and these responses were attenuated in SHR. Vasopressin immunoreactivity in the PVN was also increased by physical training to a lesser extent in SHR. The already-reduced oxytocin expression in the PVN of SHR was increased in response to physical training. Within the SON, neuronal activation and the expressions of vasopressin and oxytocin were reduced by hypertension and unaffected by physical training. The data indicate that physical training counterbalances in part the negative effect of hypertension on hypothalamic neuronal activation elicited by exercise, as well as on the expression of vasopressin and oxytocin. These hypertension features seem to negatively influence the workload performed by SHR due to the hyperthermia derived from the inability of physical training to improve heat dissipation through skin vasodilation.

Effects of physical exercise combined with captopril or losartan on left ventricular hypertrophy of hypertensive rats

ABSTRACT Background: Left ventricular hypertrophy (LVH) is an endpoint of hypertensive cardiac alterations. Renin-angiotensin-aldosterone system (RAAS) blockers are among the most effective on LVH regression. Physical exercise combined to antihypertensive drug contributes to arterial pressure (AP) control and LVH prevention. We evaluated the effects of physical exercise combined to captopril or losartan during eight weeks for spontaneously hypertensive rats (SHR) on some cardiac parameters. Methods: SHR (n=5-6 per group) were sedentary or trained 5 days a week in treadmill during 8 weeks; and they were treated with daily oral captopril (12.5, 25, or 50mg/kg), losartan (2.5, 5, or 10mg/kg), or vehicle. At the end, it was obtained systolic AP (SAP), electrocardiogram (ECG), and hearts metalloproteinase 2 (MMP-2) activity and histology. Results: Captopril 25 and 50 mg/kg, and losartan 10 mg/kg lowered SAP of sedentary and trained SHR. Losartan 5 mg/kg combined with physical exercise also lowered SAP. Combined with exercise, captopril 50 mg/kg lowered 13.6% of QT interval, 14.2% of QTc interval, and 22.8% of Tpeak-Tend compared to sedentary SHR. Losartan 5 and 10mg/kg lowered QT interval of sedentary and trained SHR. Losartan 2.5, 5 and 10mg/kg combined with physical exercise lowered respectively 25.4%, 24.8%, and 31.8% of MMP-2 activity. Losartan (10mg/kg) combined with exercise reduced cardiomyocyte diameter. Conclusion: These data support the hypothesis of physical exercise combined with RAAS blockers could improve the benefits on hypertensive LVH treatment.

Exercise Prevents Hypertension and Disrupts the Correlation Between Vascular Sympathetic Activity and Age-Related Increase in Blood Pressure in SHRs.

Hypertension usually accompanies the elevated sympathetic activity and sleep interruption. Few researches explored the dynamic changes and possible correlations in cardiovascular functions and sleep patterns during the development of hypertension. In contrast, exercise training provides several benefits on cardiovascular and sleep function in hypertensive subjects. However, controlling various factors during a long period of exercise training is difficult in hypertensive subjects, an animal model may be essential. This study aimed to explore dynamic changes in cardiovascular functions and sleep patterns during the development period of hypertension (10-20 weeks old) in spontaneously hypertensive rats (SHRs) and effects of exercise intervention. We used the treadmill exercise model for 8 weeks and started when SHRs were 12 weeks old. Electroencephalogram, electromyogram, electrocardiogram, and blood pressure (BP) were recorded simultaneously for 24 hours once a week over 11 weeks. Untrained SHRs revealed the age-related increments in BP, and the significant increasing slopes of differences on BP and vascular sympathetic activity were observed during the development period of hypertension. Compared with untrained rats, age-related increases in BP and vascular sympathetic activity were significantly suppressed in trained SHRs. Nevertheless, trained SHRs showed more quiet sleep time at partial weeks. The positive correlation between the differences from 10 weeks of vascular sympathetic activity and BP was disappeared in trained SHRs. There existed the significant correlation between the dynamic changes of vascular sympathetic activity and age-related elevation of BP during the development period of hypertension; however, exercise prevented hypertension and disrupted this correlation.

Thermoregulation in Hypertensive Rats during Exercise: Effects of Physical Training

BackgroundSpontaneously hypertensive rats (SHR) show deficit in thermal balance during physical exercise.ObjectiveTo assess the effects of low-intensity physical exercise training on thermal balance of hypertensive rats undergoing an acute exercise protocol.MethodsSixteen-week-old male Wistar rats and SHR were allocated into four groups: control Wistar rats (C-WIS), trained Wistar (T-WIS), control SHR (C-SHR) and trained SHR (T-SHR). Treadmill exercise training was performed for 12 weeks. Blood pressure, resting heart rate and total exercise time was measured before and after the physical exercise program. After the exercise program, a temperature sensor was implanted in the abdominal cavity, and the animals subjected to an acute exercise protocol, during which internal body temperature, tail skin temperature and oxygen consumption until fatigue were continuously recorded. Mechanical efficiency (ME), work, heat dissipation threshold and sensitivity were calculated. Statistical significance was set at 5%.ResultsPhysical training and hypertension had no effect on thermal balance during physical exercise. Compared with C-WIS, the T-WIS group showed higher heat production, which was counterbalanced by higher heat dissipation. Hypertensive rats showed lower ME than normotensive rats, which was not reversed by the physical training.ConclusionLow-intensity physical training did not affect thermal balance in SHR subjected to acute exercise.

A1222 Exercise training enhances baroreflex and depressor via activation of central ACE2-Ang(1–7)-Mas axis in SHR

Objectives: To investigate the effects of exercise training on the development and progression of hypertension, blood pressure regulation and the gene and protein expression of angiotensin converting enzyme 2 (ACE2) and MAS receptors in the paraventricular nucleus (PVN). Methods: Male 6 weeks of old spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were randomly assigned to the sedentary (Sed) or the exercise training (ExT) group. Exercise training was performed on a treadmill for 20 weeks (18–20 m/min, 60 min/d, 5d/wk). Blood pressure, baroreflex sensitivity (BRS) and the mRNA and protein expression of ACE2 and Mas receptors in the PVN were determined. Alterations of BRS were evaluated before and after intracerebroventricular (ICV) injection of angiotensin1–7 (Ang1–7) and its antagonist A779, respectively. Results: BP was over 140mmHg in the 8th wk of SHR + Sed, but exercise training postponed 2 weeks of the development of hypertension and retarded hypertension progression in SHR. Also, exercise training prevented the decrease in BRS in the SHR + ExT compared with SHR + Sed (P < 0.01). ICV injection of A779 inhibited the BRS in SHR + ExT, which abolished the benefits of exercise training (P < 0.01), but had no influence in SHR + Sed. In contrast, angiotensin1–7 enhanced BRS in sedentary and trained SHR (P < 0.05). Exercise training up-regulated the mRNA and protein expression of ACE2 and Mas receptors in the PVN in SHR, buy not in WKY (P < 0.01). Conclusion: Early exercise training postpones the progression of prehypertension and improves blood pressure regulation, which is associated with the enhanced function of central ACE2-Ang (1–7)-Mas axis. (Support by the National Natural Science Foundation of China (No.81372111) and the Natural Science Foundation of Fujian Province (No.2014 J01339)

Training Attenuated Hypertension in Dexamethasone‐Treated Wistar Rats and SHR Through Different Mechanisms

It has been shown that chronic treatment with dexamethasone (DEX) increase blood pressure (BP) in normotensive rats, however, nothing is known about the effects of DEX treatment in spontaneously hypertensive rats (SHR). On the other hand, exercise training (T) has been recommended as a non‐pharmacological treatment for hypertension. Thus, the aim of this study was to investigate the preventive role of T in counteracting DEX‐induced BP increase in normotensive and SHR. Rats were randomly allocated into 8 groups: Wistar sedentary control (WSC), Wistar sedentary treated with DEX (WSD), Wistar trained control (WTC), Wistar trained and treated with DEX (WTD), SHR sedentary control (SHRSC), SHR sedentary treated with DEX (SHRSD), SHR trained control (SHRTC) and SHR trained and treated with DEX (SHRTD). All groups underwent T protocol (treadmill, 60% of physical capacity, 5 days/week, 8 weeks) or were kept sedentary. Then, rats were treated with DEX or saline (0.05 mg/kg per day, s.c., 14 days). Systolic arterial pressure (SAP) was measured by carotid artery catheterization and cardiovascular autonomic modulation to the heart was evaluated by spectral analysis. In addition, tibialis anterior (TA) muscle was collected for morphometric analysis. In Wistar rats, DEX treatment increased SAP (130 ± 5 vs 106 ± 6 mmHg, for SD vs SC, respectively) associated with an increase in low‐frequency spectral power (LF) (45.1 ± 5.9 vs 18.7 ± 4.8 nu, for SD vs SC, respectively) and a decrease in high‐frequency (HF) spectral power (54.8 ± 5.9 vs 81.2 ± 4.8 nu, for SD vs SC, respectively) of pulse interval; also DEX decreased capillary‐to‐fiber ratio (C:F ratio) (0.7 ± 0.02 vs 0.9 ± 0.01, for SD vs SC, respectively) in TA muscle, without affecting wall‐to‐lumen ratio (W/L ratio). Although SHR presented higher SAP (149 ± 7 vs 106 ± 6 mmHg, for SHRSC vs WSC, respectively) and W/L ratio (0.91 ± 0.09 vs 0.58 ± 0.08, for SHRSC vs WSC, respectively) as well as lower values of C:F ratio (0.7 ± 0.04 vs 0.9 ± 0.01, for SHRSC vs WSC, respectively), compared with Wistar rats, DEX treatment did not produce any further alterations in these parameters. On the other hand, T, in Wistar rats, was able to attenuate SAP increase (122 ± 4 vs 130 ± 5 mmHg, for TD vs SD, respectively), LF increase (27.6 ± 6.2 vs 45.1 ± 5.9 nu, for TD vs SD, respectively), HF decrease (72.3 ± 6.2 vs 54.8 ± 5.9 nu, for TD vs SD, respectively) of pulse interval and also C:F ratio decrease (1.0 ± 0.02 vs 0.7 ± 0.02, for TD vs SD, respectively) in TA muscle. In addition, in SHR, T was effective to reduce SAP (121 ± 5 vs 151 ± 8 mmHg, for TD vs SD, respectively), to increase C:F ratio (1.0 ± 0.04 vs 0.7 ± 0.02, for TD vs SD, respectively) and to decrease arterioles W/L ratio (0.58 ± 0.09 vs 0.91 ± 0.08, for TD vs SD, respectively) in TA muscle. In conclusion, these results allow us to suggest that T was able to attenuate DEX‐induced BP increase in Wistar rats, associated with an improvement of cardiovascular autonomic modulation and skeletal muscle microcirculation. In addition, T was able to decrease BP in SHR, mainly through decreases in arterioles W/L ratio and improvements in microcirculation, independent of DEX treatment.Support or Funding InformationSão Paulo Research FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Maintenance of Blood-Brain Barrier Integrity in Hypertension: A Novel Benefit of Exercise Training for Autonomic Control.

The blood-brain barrier (BBB) is a complex multicellular structure acting as selective barrier controlling the transport of substances between these compartments. Accumulating evidence has shown that chronic hypertension is accompanied by BBB dysfunction, deficient local perfusion and plasma angiotensin II (Ang II) access into the parenchyma of brain areas related to autonomic circulatory control. Knowing that spontaneously hypertensive rats (SHR) exhibit deficient autonomic control and brain Ang II hyperactivity and that exercise training is highly effective in correcting both, we hypothesized that training, by reducing Ang II content, could improve BBB function within autonomic brain areas of the SHR. After confirming the absence of BBB lesion in the pre-hypertensive SHR, but marked fluorescein isothiocyanate dextran (FITC, 10 kD) leakage into the brain parenchyma of the hypothalamic paraventricular nucleus (PVN), nucleus of the solitary tract, and rostral ventrolateral medulla during the established phase of hypertension, adult SHR, and age-matched WKY were submitted to a treadmill training (T) or kept sedentary (S) for 8 weeks. The robust FITC leakage within autonomic areas of the SHR-S was largely reduced and almost normalized since the 2nd week of training (T2). BBB leakage reduction occurred simultaneously and showed strong correlations with both decreased LF/HF ratio to the heart and reduced vasomotor sympathetic activity (power spectral analysis), these effects preceding the appearance of resting bradycardia (T4) and partial pressure fall (T8). In other groups of SHR-T simultaneously infused with icv Ang II or saline (osmotic mini-pumps connected to a lateral ventricle cannula) we proved that decreased local availability of this peptide and reduced microglia activation (IBA1 staining) are crucial mechanisms conditioning the restoration of BBB integrity. Our data also revealed that Ang II-induced BBB lesion was faster within the PVN (T2), suggesting the prominent role of this nucleus in driven hypertension-induced deficits. These original set of data suggest that reduced local Ang II content (and decreased activation of its downstream pathways) is an essential and early-activated mechanism to maintain BBB integrity in trained SHR and uncovers a novel beneficial effect of exercise training to improve autonomic control even in the presence of hypertension.

Effects of 6-months' Exercise on Cardiac Function, Structure and Metabolism in Female Hypertensive Rats-The Decisive Role of Lysyl Oxidase and Collagen III.

Purpose: According to the current therapeutic guidelines of the WHO physical activity and exercise are recommended as first-line therapy of arterial hypertension. Previous results lead to the conclusion, however, that hearts of spontaneously hypertensive rats (SHR) with established hypertension cannot compensate for the haemodynamic stresses caused by long-term exercise. The current study was initiated to investigate the effects of aerobic exercise on the cardiac remodeling as the sole therapeutic measure before and during hypertension became established.Methods: Beginning at their 6th week of life, six SHR were provided with a running wheel over a period of 6 months. Normotensive Wistar rats served as non-hypertensive controls.Results: In Wistar rats and SHR, voluntary exercise led to cardioprotective adaptation reactions that were reflected in increased mitochondrial respiration, reduced heart rate and improved systolic function. Exercise also had antioxidant effects and reduced the expression of maladaptive genes (TGF-β1, CTGF, and FGF2). However, at the end of the 6-months' training, the echocardiograms revealed that SHR runners developed a restrictive cardiomyopathy. The induction of lysyl oxidase (LOX), which led to an increased network of matrix proteins and a massive elevation in collagen III expression, was identified as the underlying cause.Conclusions: Running-induced adaptive mechanisms effectively counteract the classic remodeling of hearts subject to chronic pressure loads. However, with sustained running stress, signaling pathways are activated that have a negative effect on left ventricular relaxation. Our data suggest that the induction of LOX may play a causative role in the diagnosed filling disorder in trained SHR.

Association of exercise training and angiotensin-converting enzyme 2 activator improves baroreflex sensitivity of spontaneously hypertensive rats

The present study sought to determine cardiovascular effects of aerobic training associated with diminazene aceturate (DIZE), an activator of the angiotensin converting enzyme 2, in spontaneously hypertensive rats (SHRs). Male SHRs (280–350 g) were either subjected to exercise training or not (sedentary group). The trained group was subjected to 8 weeks of aerobic training on a treadmill (five times a week, lasting 60 min at an intensity of 50–60% of maximum aerobic speed). In the last 15 days of the experimental protocol, these groups were redistributed into four groups: i) sedentary SHRs with daily treatment of 1 mg/kg DIZE (S+D1); ii) trained SHRs with daily treatment of 1 mg/kg DIZE (T+D1); iii) sedentary SHRs with daily treatment of vehicle (S+V); and iv) trained SHRs with daily treatment of vehicle (T+V). After treatment, SHRs were anesthetized and subjected to artery and femoral vein cannulation prior to the implantation of ECG electrode. After 24 h, mean arterial pressure (MAP) and heart rate (HR) were recorded; the baroreflex sensitivity and the effect of double autonomic blockade (DAB) were evaluated in non-anesthetized SHRs. DIZE treatment improved baroreflex sensitivity in the T+D1 group as compared with the T+V and S+D1 groups. The intrinsic heart rate (IHR) and MAP were reduced in T+D1 group as compared with T+V and S+D1 groups. Hence, we conclude that the association of exercise training with DIZE treatment improved baroreflex function and cardiovascular regulation.

Response Analysis of Hemodynamics Parameters to Tyramine Infusion Post‐Exercise Training in Spountaneously Hypertensive Rats

The aim of the study was to assess the effects of exercise training in the vascular control after sympathetic stimulation mimicked by tyramine infusion in spontaneously hypertensive rats (SHR). Thirty two male SHR and wistar kyoto were submitted or not to a swimming protocol, resulting in four groups: sedentary normotensive (SN), trained normotensive (TN), sedentary hypertensive (SH) and trained hypertensive (TH). Arterial pressure (AP), heart rate (HR), power spectral analysis of HR (HRV), systolic AP variability (SAPV) and diastolic (DAPV) were recorded in baseline conditions. Following, the infusion of tyramine was administrated. Resting bradycardia was observed in both TN and TH rats compared with their respective sedentary animals. Exercise training attenuated AP in TH vs. SH. The variance of HRV was lower in SH vs. TH. The variance of SAPV and DAPV were higher in SH vs. TH. The LF component of HRV, SAPV and DAPV were lower in TH than SH. The pressor response to tyramine was enhanced in trained SHR but not kyoto. In conclusion, the results points to a sympatolitic effect of exercise training, probably at pre synaptic level, suggesting an up regulation of α&lt;sub style=”text‐align: start;”&gt;1‐receptors in vascular smooth muscle. These findings showed that exercise training may be a therapeutic tool for improving function in hypertensive individuals.

Aerobic exercise training increases neuronal nitric oxide release and bioavailability and decreases noradrenaline release in mesenteric artery from spontaneously hypertensive rats

To study the effect of aerobic exercise training on sympathetic, nitrergic and sensory innervation function in superior mesenteric artery from spontaneously hypertensive rats (SHRs). De-endothelized vascular rings from sedentary and trained SHRs (treadmill 12 weeks) were used. Vasomotor responses to electrical field stimulation (EFS), noradrenaline, nitric oxide donor DEA-NO and calcitonin gene-related peptide (CGRP) were studied. Neuronal nitric oxide synthase (nNOS) expression and nitric oxide, superoxide anions (O(2.-)), noradrenaline and CGRP levels were also determined. Aerobic exercise training decreased vasoconstrictor response to EFS but increased noradrenaline response. Phentolamine decreased while N(ω)-nitro-(L)-arginine methyl ester ((L)-NAME) increased the response to EFS; the effect of both drugs was greater in trained animals. Training also decreased noradrenaline release and O(2.-) production and increased nNOS expression, nitric oxide release and the vasodilator response to DEA-NO. The O(2.-) scavenger tempol increased DEA-NO-induced vasodilation only in sedentary rats. The EFS-induced contraction was increased to a similar extent in both experimental groups by preincubation with CGRP (8-37). CGRP release and vasodilator response were not modified by training. Aerobic exercise training decreases contractile response to EFS in mesenteric artery from SHRs. This effect is the net result of decreased noradrenaline release, increased sensitivity to the vasoconstrictive effects of noradrenaline and increased neuronal nitric oxide release and bioavailability. These modifications might contribute to the beneficial effects of aerobic exercise training on blood pressure.

Long-term exercise attenuates blood pressure responsiveness and modulates kidney angiotensin II signalling and urinary sodium excretion in SHR

Observations have been made regarding the effects of long-term exercise training on blood pressure, renal sodium handling and renal renin-angiotensin-aldosterone (RAS) intracellular pathways in conscious, trained Okamoto-Aoki spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKy) normotensive rats, compared with appropriate age-matched sedentary SHR and WKy. To evaluate the influence of exercise training on renal function and RAS, receptors and intracellular angiotensin II (AngII) pathway compounds were used respectively, and lithium clearance and western blot methods were utilised. The current study demonstrated that increased blood pressure in SHR was blunted and significantly reduced by long-term swim training between the ages of 6 and 16 weeks. Additionally, the investigators observed an increased fractional urinary sodium excretion in trained SHR (SHR(T)) rats, compared with sedentary SHR (SHR(S)), despite a significantly decreased creatinine clearance (C(Cr)). Furthermore, immunoblotting analysis demonstrated a decreased expression of AT1(R) in the entire kidney of T(SHR) rats, compared with S(SHR). Conversely, the expression of the AT2(R), in both sedentary and trained SHR, was unchanged. The present study may indicate that, in the kidney, long-term exercise exerts a modulating effect on AngII receptor expression. In fact, the present study indicates an association of increasing natriuresis, reciprocal changes in renal AngII receptors and intracellular pathway proteins with the fall in blood pressure levels observed in T(SHR) rats compared with age-matched S(SHR) rats.

Effect of gender on training-induced vascular remodeling in SHR

There is accumulating evidence that physical inactivity, associated with the modern sedentary lifestyle, is a major determinant of hypertension. It represents the most important modifiable risk factor for cardiovascular diseases, which are the leading cause of morbidity and mortality for both men and women. In addition to involving sympathetic overactivity that alters hemodynamic parameters, hypertension is accompanied by several abnormalities in the skeletal muscle circulation including vessel rarefaction and increased arteriole wall-to-lumen ratio, which contribute to increased total peripheral resistance. Low-intensity aerobic training is a promising tool for the prevention, treatment and control of high blood pressure, but its efficacy may differ between men and women and between male and female animals. This review focuses on peripheral training-induced adaptations that contribute to a blood pressure-lowering effect, with special attention to differential responses in male and female spontaneously hypertensive rats (SHR). Heart, diaphragm and skeletal muscle arterioles (but not kidney arterioles) undergo eutrophic outward remodeling in trained male SHR, which contributed to a reduction of peripheral resistance and to a pressure fall. In contrast, trained female SHR showed no change in arteriole wall-to-lumen ratio and no pressure fall. On the other hand, training-induced adaptive changes in capillaries and venules (increased density) were similar in male and female SHR, supporting a similar hyperemic response to exercise.

Brainstem oxytocinergic modulation of heart rate control in rats: effects of hypertension and exercise training

Oxytocinergic brainstem projections participate in the autonomic control of the circulation. We investigated the effects of hypertension and training on cardiovascular parameters after oxytocin (OT) receptor blockade within the nucleus tractus solitarii (NTS) and NTS OT and OT receptor expression. Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were trained (55% of maximal exercise capacity) or kept sedentary for 3 months and chronically instrumented (NTS and arterial cannulae). Mean arterial blood pressure (MAP) and heart rate (HR) were measured at rest and during an acute bout of exercise after NTS pretreatment with vehicle or OT antagonist (20 pmol of OT antagonist (200 nl of vehicle)(-1)). Oxytocin and OT receptor were quantified ((35)S-oligonucleotide probes, in situ hybridization) in other groups of rats. The SHR exhibited high MAP and HR (P < 0.05). Exercise training improved treadmill performance and reduced basal HR (on average 11%) in both groups, but did not change basal MAP. Blockade of NTS OT receptor increased exercise tachycardia only in trained groups, with a larger effect on trained WKY rats (+31 +/- 9 versus +12 +/- 3 beats min(1) in the trained SHR). Hypertension specifically reduced NTS OT receptor mRNA density (-46% versus sedentary WKY rats, P < 0.05); training did not change OT receptor density, but significantly increased OT mRNA expression (+2.5-fold in trained WKY rats and +15% in trained SHR). Concurrent hypertension- and training-induced plastic (peptide/receptor changes) and functional adjustments (HR changes) of oxytocinergic control support both the elevated basal HR in the SHR group and the slowing of the heart rate (rest and exercise) observed in trained WKY rats and SHR.

Exercise Training Reduces Sympathetic Modulation on Cardiovascular System and Cardiac Oxidative Stress in Spontaneously Hypertensive Rats

Spontaneously hypertensive rats (SHRs) show increased cardiac sympathetic activity, which could stimulate cardiomyocyte hypertrophy, cardiac damage, and apoptosis. Norepinephrine (NE)-induced cardiac oxidative stress seems to be involved in SHR cardiac hypertrophy development. Because exercise training (ET) decreases sympathetic activation and oxidative stress, it may alter cardiac hypertrophy in SHR. The aim of this study was to determine, in vivo, whether ET alters cardiac sympathetic modulation on cardiovascular system and whether a correlation exists between cardiac oxidative stress and hypertrophy. Male SHRs (15-weeks old) were divided into sedentary hypertensive (SHR, n = 7) and exercise-trained hypertensive rats (SHR-T, n = 7). Moderate ET was performed on a treadmill (5 days/week, 60 min, 10 weeks). After ET, cardiopulmonary reflex responses were assessed by bolus injections of 5-HT. Autoregressive spectral estimation was performed for systolic arterial pressure (SAP) with oscillatory components quantified as low (LF: 0.2-0.75 Hz) and high (HF: 0.75-4.0 Hz) frequency ranges. Cardiac NE concentration, lipid peroxidation, antioxidant enzymes activities, and total nitrates/nitrites were determined. ET reduced mean arterial pressure, SAP variability (SAP var), LF of SAP, and cardiac hypertrophy and increased cardiopulmonary reflex responses. Cardiac lipid peroxidation was decreased in trained SHRs and positively correlated with NE concentrations (r = 0.89, P < 0.01) and heart weight/body weight ratio (r = 0.72, P < 0.01), and inversely correlated with total nitrates/nitrites (r = -0.79, P < 0.01). Moreover, in trained SHR, cardiac total nitrates/nitrites were inversely correlated with NE concentrations (r = -0.82, P < 0.01). ET attenuates cardiac sympathetic modulation and cardiac hypertrophy, which were associated with reduced oxidative stress and increased nitric oxide (NO) bioavailability.

Selective increase of angiotensin(1–7) and its receptor in hearts of spontaneously hypertensive rats subjected to physical training

In the present study we investigated the effects of physical training on plasma and cardiac angiotensin(1–7) [Ang(1–7)] levels. In addition, possible changes in expression of the Ang(1–7) Mas receptor in the heart were also evaluated. Normotensive Wistar rats and spontaneously hypertensive rats (SHR) were subjected to an 8 week period of 5% overload swimming training. Blood pressure was determined by a tail‐cuff system. Heart and left ventricle weights and cardiomyocyte diameter were analysed to evaluate cardiac hypertrophy. Radioimmunoassay was used to measure angiotensin levels. Expression of Mas was determined by semi‐quantitative polymerase chain reaction, immunofluorescence and Western blotting. Physical training induced cardiac hypertrophy in Wistar rats and SHR. A significant decrease of plasma angiotensin II (Ang II) levels in both strains was also observed. Strikingly, trained SHR, but not trained Wistar rats, showed a twofold increase in left ventricular Ang(1–7) levels. No significant changes were observed in plasma Ang(1–7) and left ventricular Ang II concentrations in either strain. Furthermore, Mas mRNA and protein expression in left ventricle were substantially increased in trained SHR. The physical training protocol used did not change blood pressure in either strain. These results suggest that the beneficial effects induced by swimming training in hypertensive rats might include an augmentation of Ang(1–7) and its receptor in the heart.

Selective increase of angiotensin(1-7) and its receptor in hearts of spontaneously hypertensive rats subjected to physical training

In the present study we investigated the effects of physical training on plasma and cardiac angiotensin(1-7) [Ang(1-7)] levels. In addition, possible changes in expression of the Ang(1-7) Mas receptor in the heart were also evaluated. Normotensive Wistar rats and spontaneously hypertensive rats (SHR) were subjected to an 8 week period of 5% overload swimming training. Blood pressure was determined by a tail-cuff system. Heart and left ventricle weights and cardiomyocyte diameter were analysed to evaluate cardiac hypertrophy. Radioimmunoassay was used to measure angiotensin levels. Expression of Mas was determined by semi-quantitative polymerase chain reaction, immunofluorescence and Western blotting. Physical training induced cardiac hypertrophy in Wistar rats and SHR. A significant decrease of plasma angiotensin II (Ang II) levels in both strains was also observed. Strikingly, trained SHR, but not trained Wistar rats, showed a twofold increase in left ventricular Ang(1-7) levels. No significant changes were observed in plasma Ang(1-7) and left ventricular Ang II concentrations in either strain. Furthermore, Mas mRNA and protein expression in left ventricle were substantially increased in trained SHR. The physical training protocol used did not change blood pressure in either strain. These results suggest that the beneficial effects induced by swimming training in hypertensive rats might include an augmentation of Ang(1-7) and its receptor in the heart.

Baroreflex sensitivity improvement is associated with decreased oxidative stress in trained spontaneously hypertensive rat

Baroreflex sensitivity (BRS) impairment has been associated with endothelial dysfunction and oxidative stress. Because exercise training could improve endothelial function in spontaneously hypertensive rats (SHR), the effect of moderate exercise training on oxidative stress and BRS was investigated. Groups were divided into sedentary and trained Wistar-Kyoto rats (S-WK, n = 7 and T-WK, n = 6) and SHR (S-SHR and T-SHR, n = 9 each). Exercise training was performed on a treadmill (5 days/week, 60 min, 10 weeks), and the lactate threshold (20 m/min) was used to determine moderate intensity. Exercise training reduced mean arterial pressure in WK and SHR (S-WK 127 +/- 4, T-WK 105 +/- 5, S-SHR 169 +/- 4 versus T-SHR 140 +/- 4 mmHg; P < 0.01). Baroreflex bradycardic (S-WK -1.89 +/- 0.15, T-WK -2.11 +/- 0.37, S-SHR -0.80 +/- 0.09 versus T-SHR -1.29 +/- 0.10 bpm/mmHg; P < 0.0001) and tachycardic (S-WK 2.57 +/- 0.19, T-WK 2.73 +/- 0.21, S-SHR 1.18 +/- 0.07 versus T-SHR 2.02 +/- 0.10 bpm/mmHg; P < 0.0001) responses were significantly different between groups. Lipoperoxidation in erythrocytes (S-WK 11 320 +/- 739, T-WK 10 397 +/- 765, S-SHR 20 511 +/- 1627 versus T-SHR 10 211 +/- 589 counts per second (cps)/mg haemoglobin; P < 0.0001) and aortas (S-WK 12 424 +/- 2219, T-WK 7917 +/- 726, S-SHR 26 957 +/- 1772 versus T-SHR 17 777 +/- 1923 cps/mg protein; P < 0.0001) was reduced in T-SHR compared with S-SHR. Inverse correlations were observed between both bradycardic and tachycardic responses and lipoperoxidation in erythrocytes (r = 0.56 and r = -0.77, respectively; P < 0.01) and aortas (r = 0.77 and r = -0.80, respectively; P < 0.0001). Our results indicate that exercise training decreases oxidative stress, which is related to an improvement in BRS in SHR.

Effect of endurance training on atrial natriuretic peptide gene expression in normal and hypertrophied hearts.

We studied the effects of physical endurance training on atrial natriuretic peptide (ANP) gene expression in beagle dogs, Wistar rats, and spontaneously hypertensive rats (SHR). The dogs underwent a gradually increased running training up to 40 km/day on a treadmill for 55 wk while the nontrained sibling control dogs were kept in their cages throughout the study. Endurance training caused a significant 13% (P < 0.05) increase in ventricular hypertrophy but did not change plasma immunoreactive (ir)-ANP levels at rest or ventricular ANP mRNA or irANP levels. When normotensive Wistar rats ran up to 2,200 m/day for 8 wk, no significant change was seen in ventricular hypertrophy or in plasma or ventricular irANP levels at rest compared with nontrained controls. However, endurance training caused a 2.2-fold increase in epicardial ANP mRNA levels (P < 0.05). In the SHR strain, running training up to 900 m/day for 31 wk increased ventricular hypertrophy of trained SHR by 7% (P < 0.01) and caused a concomitant 1.6- to 1.7-fold elevation in ventricular irANP and ANP mRNA levels (P < 0.01-0.001) compared with nontrained SHR. In contrast, changes in atrial ANP mRNA or irANP levels in response to training were small in all three protocols. This study shows that in the normal heart induction of ANP synthesis by endurance training is not associated with ventricular hypertrophy. Moreover, the common stimulus for ventricular ANP synthesis induced by both chronic pressure overload and physical training may be mechanical stretching of cardiac myocytes, because endurance training further stimulated ANP synthesis in hypertrophied ventricles in SHR.

Effects of voluntary exercise on bone growth and calcium metabolism in spontaneously hypertensive rats.

The effects of voluntary exercise on bone length and calcium metabolism were investigated in spontaneously hypertensive rats (SHR) and Wistar rats. They were classified into voluntary exercise or sedentary group. Systolic blood pressure (SBP), bone length, urinary calcium excretion, plasma calcium and parathyroid hormone levels (PTH) were measured for analysis. SBP of the trained SHR (T-SHR) was significantly lower than that of the nontrained SHR (NT-SHR) at 10 and 11 weeks of age, but the trained Wistar rats (T-WR) and the nontrained Wistar rats (NT-WR) had similar SBP throughout the experimental period. The T-SHR had significantly longer bones in the extremities and the trunk than the NT-SHR, whereas the T-WR had similar or shorter bones than the NT-WR. The PTH level at 12 weeks of age was significantly lower in the T-SHR than in the NT-SHR. The urinary calcium excretion of the T-SHR was greater than that of the NT-SHR, but the food intake (calcium intake) of the T-SHR was also greater. The urinary calcium excretion and food intake of the T-WR and NT-WR were similar. No noticeable differences were observed in the plasma calcium level between the T-SHR and NT-SHR, the T-WR and NT-WR. From these results it is suggested that the abnormal calcium metabolism in the SHR is improved in some degree by voluntary exercise.