What do we know about the role of menopause in cardiovascular autonomic regulation in hypertensive women?

OBJECTIVE: We investigated the systemic arterial hypertension effects on cardiovascular autonomic modulation and baroreflex sensitivity (BRS) in women with or without preserved ovarian function. METHODS: A total of 120 women were allocated into two groups: middle-aged premenopausal women (42 ± 3 y old; n = 60) and postmenopausal women (57 ± 4 y old; n = 60). Each group was also divided into two smaller groups (n = 30): normotensive and hypertensive. We evaluated hemodynamic and anthropometric parameters, cardiorespiratory fitness, BRS, heart rate variability (HRV), and blood pressure variability. The effects of hypertension and menopause were assessed using a two-way analysis of variance. Post hoc comparisons were performed using the Student-Newman-Keuls test. RESULTS: Comparing premenopausal groups, women with systemic arterial hypertension showed lower BRS (9.1 ± 4.4 vs 13.4 ± 4.2 ms/mm Hg, P < 0.001 ) and HRV total variance (1,451 ± 955 vs 2,483 ± 1,959 ms 2 , P = 0.005) values than normotensive; however, the vagal predominance still remained. On the other hand, both postmenopausal groups showed an expressive reduction in BRS (8.3 ± 4.2 vs 11.3 ± 4.8 ms/mm Hg, P < 0.001) and HRV characterized by sympathetic modulation predominance (low-frequency oscillations; 56% ± 17 vs 44% ± 17, P < 0.001), in addition to a significant increase in blood pressure variability variance (28.4 ± 14.9 vs 22.4 ± 12.5 mm Hg 2 , P = 0.015) compared with premenopausal groups. Comparing both postmenopausal groups, the hypertensive group had significantly lower values ​​of HRV total variance (635 ± 449 vs 2,053 ± 1,720 ms 2 , P < 0.001) and BRS (5.3 ± 2.8 vs 11.3 ± 3.2 ms/mm Hg) than the normotensive. CONCLUSIONS: Hypertensive middle-aged premenopausal women present HRV autonomic modulation impairment, but they still maintain a vagal predominance. After menopause, even normotensive women show sympathetic autonomic predominance, which may also be associated with aging. Furthermore, postmenopausal women with hypertension present even worse cardiac autonomic modulation.

Physical exercise is essential for increasing ventricular contractility in hypertensive rats treated with losartan.

The treatment of hypertensive patients with losartan is very common. Despite the reduction in blood pressure, its effects on cardiac contractility and sympathetic autonomic drive are still controversial. In turn, aerobic physical training (APT) also presents an important therapeutic option, providing significant improvements in cardiovascular autonomic control, however little is known about its effects on cardiac contractility, especially when associated with losartan. Therefore, we investigated in spontaneously hypertensive rats (SHR) the effects of losartan and APT on cardiac hemodynamics and functionality, with emphasis on autonomic tonic balance and cardiac contractility. Sixty-four SHR (18 weeks old) were divided into four groups (N = 16): vehicle; vehicle submitted to APT through swimming for 12 weeks; treated with losartan (5 mg·kg-1·d-1) for 12 weeks; and treated with losartan associated with APT. The groups were submitted to cardiac morphological and functional analysis by echocardiography; double blockade of cardiac autonomic receptors with atropine and propranolol; and coronary bed reactivity and left ventricular contractility analyses by the Langendorff technique. APT improved functional parameters and autonomic balance by reducing sympathetic drive and/or increasing vagal drive. In contrast, it promoted a concentric remodeling of the left ventricle (LV). Treatment with losartan reduced sympathetic autonomic drive and cardiac morphological parameters, but there were no significant gains in cardiac functionality and contractility. When combined, the concentric remodeling of the LV to APT was abolished and gains in cardiac functionality and contractility were observed. Our findings suggest that the effects of losartan and APT are complementary and should be applied together in the treatment of hypertension. In spontaneously hypertensive rats, the combination of aerobic physical training with losartan treatment was crucial to greater blood pressure reductions and an increase in left ventricular contractility. Furthermore, losartan treatment prevented the concentric left ventricular remodeling caused by aerobic physical training.

Glucose-sensitive hypothalamic nuclei traced through functional magnetic resonance imaging.

Introduction: Hypothalamic glucose-sensitive neural circuits, which regulate energy metabolism and can contribute to diseases such as obesity and type 2 diabetes, have been difficult to study in humans. We developed an approach to assess hypothalamic functional connectivity changes during glucose loading using functional magnetic resonance imaging (fMRI). Methods: To do so, we conducted oral glucose tolerance tests while acquiring functional images before, and 10 and 45 min after glucose ingestion in a healthy male and cross-sectionally in 20 healthy participants on two different diets. Results: At group level, 39 fMRI sessions were not sufficient to detect glucose-mediated connectivity changes. However, 10 repeated sessions in a single subject revealed significant intrinsic functional connectivity increases 45 min after glucose intake in the arcuate, paraventricular, and dorsomedial nuclei, as well as in the posterior hypothalamic area, median eminence, and mammillary bodies. Discussion: Our methodology allowed to outline glucose-sensitive hypothalamic pathways in a single human being and holds promise in delineating individual pathophysiology mechanisms in patients with dysglycemia.

Randomized Trial Comparing SGLT2 Inhibition and Hydrochlorothiazide on Sympathetic Traffic in Type 2 Diabetes.

Introduction: Reductions in sympathetic nervous system activity may contribute to beneficial effects of sodium glucose cotransporter 2 (SGLT2) inhibition on cardiovascular outcomes. Therefore, we tested the hypothesis that SGLT2 inhibition with empagliflozin (Empa) lowers muscle sympathetic nerve activity (MSNA) in patients with type 2 diabetes mellitus (T2DM) compared with hydrochlorothiazide (HCT) to discern SGLT2-specific actions from responses to increased natriuresis. Methods: We randomized patients with T2DM on metformin monotherapy to either 25 mg/d Empa (n = 20) or 25 mg/d HCT (n = 21) for 6 weeks in a parallel, double-blind fashion. We assessed MSNA by peroneal microneurography, blood pressure, cardiovascular and metabolic biomarkers at baseline and at the end of treatment. Results: Both drugs elicited volume depletion, as indicated by increased thoracic impedance. Compared with HCT, Empa caused 1.23 kg more body weight loss (P = 0.011) and improved glycemic control. Seated systolic blood pressure decreased with both treatments (P < 0.002). MSNA did not change significantly with either treatment; however, MSNA changes were negatively correlated with changes in body weight on Empa (P = 0.042) and on HCT(P = 0.001). The relationship was shifted to lower MSNA on Empa compared with HCT (P = 0.002). Conclusion: Increased renal sodium excretion eliciting body weight loss may promote sympathetic activation. However, sympathetic excitation in the face of increased sodium loss may be attenuated by SGLT2 inhibitor-specific actions.

Electrocardiographic changes during sustained normobaric hypoxia in patients after myocardial infarction.

The safety of prolonged high-altitude stays and exercise for physically fit post-myocardial infarction (MI) patients is unclear. Myocardial tissue hypoxia and pulmonary hypertension can affect cardiac function and electrophysiology, possibly contributing to arrhythmias. We included four non-professional male athletes, clinically stable after left ventricular MI (three with ST-segment elevation MI and one with non-ST-segment elevation MI) treated with drug-eluting stents for single-vessel coronary artery disease. Oxygen levels were reduced to a minimum of 11.8%, then restored to 20.9%. We conducted electrocardiography (ECG), ergometry, and echocardiography assessments in normoxic and hypoxic conditions. With an average age of 57.8 ± 3.3 years and MI history 37 to 104 months prior, participants experienced a significant increase in QTc intervals during hypoxia using Bazett's (from 402 ± 13 to 417 ± 25 ms), Fridericia's (from 409 ± 12 to 419 ± 19 ms), and Holzmann's formulas (from 103 ± 4 to 107 ± 6%) compared to normoxia. This effect partially reversed during recovery. Echocardiographic signs of pulmonary hypertension during normobaric hypoxia correlated significantly with altered QTc intervals (p < 0.001). Despite good health and complete revascularization following MI, susceptibility to hypoxia-induced QTc prolongation and ventricular ectopic beats persists, especially during physical activity. MI survivors planning high-altitude activities should consult cardiovascular specialists with high-altitude medicine expertise.

Cerebral blood flow autoregulation assessment by correlation analysis between mean arterial blood pressure and transcranial doppler sonography or near infrared spectroscopy is different: A pilot study.

PURPOSE: Recently, cerebral autoregulation indices based on moving correlation indices between mean arterial pressure (MAP) and cerebral oximetry (NIRS, ORx) or transcranial Doppler (TCD)-derived middle cerebral artery flow velocity (Mx) have been introduced to clinical practice. In a pilot study, we aimed to evaluate the validity of these indices using incremental lower body negative pressure (LBNP) until presyncope representing beginning cerebral hypoperfusion as well as lower body positive pressure (LBPP) with added mild hypoxia to induce cerebral hyperperfusion in healthy subjects. METHODS: Five male subjects received continuous hemodynamic, TCD and NIRS monitoring. Decreasing levels of LBNP were applied in 5-minute steps until subjects reached presyncope. Increasing levels of LBPP were applied stepwise up to 20 or 25 mmHg. Normobaric hypoxia was added until an oxygen saturation of 84% was reached. This was continued for 10 minutes. ORx and Mx indices were calculated using previously described methods. RESULTS: Both Indices showed an increase > 0.3 indicating impaired cerebral autoregulation during presyncope. However, there was no significant difference in Mx at presyncope compared to baseline (p = 0.168). Mean arterial pressure and cardiac output decreased only in presyncope, while stroke volume was decreased at the last pressure level. Neither Mx nor ORx showed significant changes during LBPP or hypoxia. Agreement between Mx and ORx was poor during the LBNP and LBPP experiments (R2 = 0.001, p = 0.3339). CONCLUSION: Mx and ORx represent impaired cerebral autoregulation, but in Mx this may not be distinguished sufficiently from baseline. LBPP and hypoxia are insufficient to reach the upper limit of cerebral autoregulation as indicated by Mx and ORx.

Aerobic Physical Exercise is Essential for Cardiac Autonomic Regulation in Hypertensive Patients Undergoing Chronic Treatment with Renin- Angiotensin System Inhibitors.

BACKGROUND: Hypertension treatment with renin-angiotensin system inhibitors (RASi) presents contradictions about the recovery of damage in cardiovascular autonomic modulation characterized by reduced heart rate variability (HRV) and increased blood pressure variability (BPV). Conversely, the association of RASi with physical training can influence achievements in cardiovascular autonomic modulation. OBJECTIVE: To investigate the effects of aerobic physical training on hemodynamics and cardiovascular autonomic modulation in hypertensive volunteers untreated and treated with RASi. METHODS: A non-randomized controlled trial in which 54 men (≅ 40-60 years old) with a history of hypertension for >2 years were allocated in accordance with their characteristics into three groups: untreated (Control; n=16), treated with type 1 angiotensin II (AT1) receptor blocker (losartan; n=21), and treated with angiotensin-converting enzyme inhibitor (enalapril; n=17). All participants underwent hemodynamic, metabolic, and cardiovascular autonomic evaluation using baroreflex sensitivity (BRS) and spectral analysis of HRV and BPV, before and after 16 weeks of supervised aerobic physical training. RESULTS: The volunteers treated with RASi had lower BPV and HRV, both in the supine position and in the tilt test, with the losartan group having the lowest values. Aerobic physical training increased HRV and BRS in all groups. However, the association of enalapril with physical training appears to be more prominent. CONCLUSION: Long-term treatment with enalapril and losartan may harm the autonomic modulation of HRV and BRS. Aerobic physical training is essential to promote positive adjustments in the autonomic modulation of HRV and BRS in hypertensive patients treated with RASi, especially with enalapril.

Impaired Physical Performance in X-linked Hypophosphatemia Is not Caused by Depleted Muscular Phosphate Stores.

CONTEXT: X-linked hypophosphatemia (XLH) is a rare genetic disease, characterized by renal phosphate wasting and complex musculoskeletal manifestations including decreased physical performance. OBJECTIVE: To characterize muscular deficits in patients with XLH and investigate phosphate stores in muscles. METHODS: Case-control study (Muscle fatigability in X-linked Hypophosphatemia [MuXLiH]) with a 1-time assessment at the German Aerospace Center (DLR), Cologne, from May to December 2019, including patients with XLH cared for at the Osteology Department, University of Wuerzburg. Thirteen patients with XLH and 13 age/sex/body weight-matched controls aged 18-65 years were included. The main outcome measure was 31P-magnetic resonance spectroscopy (31P-MRS)-based assessment of phosphate metabolites in the soleus muscle at rest. Further analyses included magnetic resonance imaging-based muscle volume measurement, laboratory testing, isokinetic maximum voluntary contraction (MVC), fatigue testing, and jumping mechanography. RESULTS: By means of 31P-MRS, no significant differences were observed between XLH and controls regarding phosphate metabolites except for a slightly increased phosphocreatine to inorganic phosphate (PCr/Pi) ratio (XLH: 13.44 ± 3.22, control: 11.01 ± 2.62, P = .023). Quadriceps muscle volume was reduced in XLH (XLH: 812.1 ± 309.0 mL, control: 1391.1 ± 306.2 mv, P < .001). No significant differences were observed regarding isokinetic maximum torque (MVC) adjusted to quadriceps muscle volume. Jumping peak power and jump height were significantly reduced in XLH vs controls (both P < .001). CONCLUSION: The content of phosphoric compounds within the musculature of patients with XLH was not observed to be different from controls. Volume-adjusted muscle strength and fatiguability were not different either. Reduced physical performance in patients with XLH may result from long-term adaptation to reduced physical activity due to skeletal impairment.

External to internal cranial perfusion shifts during simulated weightlessness: Results from a randomized cross-over trial.

The exact pathophysiology of the spaceflight-associated neuro-ocular syndrome (SANS) has so far not been completely elucidated. In this study we assessed the effect of acute head-down tilt position on the mean flow of the intra- and extracranial vessels. Our results suggest a shift from the external to the internal system that might play an important role in the pathomechanism of SANS.

Case Report: Muscle Wasting during Severe Sustained Hypoxia in Two Professional Mountaineers.

PURPOSE: Chronic exposure to hypoxia can induce muscle wasting in unaccustomed individuals. Detailed assessment of the effects of hypoxia on muscle tissue adaptation in elite mountaineers has not been performed. This study aims to assess muscle volume after exposure to normobaric hypoxia. METHODS: Two professional mountaineers (A and B) participated in a 35-d intervention of graded normobaric hypoxia with the aim of 14 d exposure to 8% oxygen corresponding to 7112-m altitude. Volume of the shank, thigh, and hip muscles was assessed by magnetic resonance imaging pre- and postintervention. Dietary intake and physical activity were monitored throughout the study from food images and accelerometry analysis, together with blood analysis and anthropometric measurements. RESULTS: Hypoxia reduced total leg muscle volume by 3.3% ± 6.0% in A and by 9.4% ± 7.3% in B. A lost 288 g and B 642 g of muscle mass, whereas dietary intake only declined by ~23% in the last intervention week. Arterial oxygen saturation declined from 95% and 86% to 77% and 72% in A and B, respectively. In hypoxia, participants could not maintain their physical activity levels. Notably, muscle loss varied substantially across muscle groups amounting to 5.4% ± 3.0%, 8.3% ± 5.2%, and 4.1% ± 8.6% for hip, thigh, and shank muscles, respectively. CONCLUSIONS: Our results indicate that hypoxia and resultant reductions in physical activity and caloric intake lead to substantial loss of muscle mass that was accentuated in proximal muscle as opposed to distal muscles. Surprisingly, thigh muscle wasting during this intervention is comparable with that observed during strict 56-d bed rest.

Cardiovascular autonomic modulation differences between moderate-intensity continuous and high-intensity interval aerobic training in women with PCOS: A randomized trial.

Background: Moderate-intensity continuous training (MICT) is strongly recommended for polycystic ovarian syndrome (PCOS) treatment. However, recent studies have suggested that high-intensity interval training (HIIT) would promote great benefits for cardiac autonomic control. Therefore, we investigated whether the benefits of HIIT related to cardiovascular autonomic control were greater than those of MICT in women with PCOS. Methods: Women with PCOS were randomly allocated through a blind draw into three groups: control, MICT, and HIIT. The control group did not undergo exercise, whereas those in the MICT and HIIT groups underwent 16 weeks of aerobic physical training. All groups were evaluated before and after the 16 weeks of intervention in the following aspects: quantification of serum lipids, testosterone, fasting insulin and blood glucose; physical fitness through cardiopulmonary testing; analysis of heart rate variability (HRV) by linear (time domain and frequency domain) and non-linear (symbolic analysis) methods, analysis of blood pressure variability (BPV) and spontaneous baroreflex sensitivity (BRS). Results: The final analysis, each group comprised 25 individuals. All groups had similar baseline parameters. After 16 weeks, intragroup comparison showed that the MICT and HIIT groups had a reduction in baseline heart rate (P < 0.001; P < 0.001, respectively) and testosterone levels P < 0.037; P < 0.012, respectively) associated with an increase in VO2peak (MICT, P < 0.001; HIIT, P < 0.001). The MICT (P < 0.36) and HIIT (P < 0.17) groups also showed an increase in cardiac vagal modulation, however only observed in the non-linear analysis. The intergroup comparison showed no differences between the MICT and HIIT groups in any of the hormonal, metabolic and autonomic parameters evaluated, including testosterone, peak oxygen uptake (VO2peak), HRV, BPV and BRS. Conclusion: HIIT and MICT showed similar results for the different parameters evaluated. This suggests that both training protocols can be recommended for the treatment of PCOS. Brazilian Clinical Trials Registry (RBR-78qtwy).

Influence of 24 h Simulated Altitude on Red Blood Cell Deformability and Hematological Parameters in Patients with Fontan Circulation.

Patients with Fontan circulation are particularly dependent on low pulmonary vascular resistance because their lungs are passively perfused. Hypoxia drives pulmonary vasoconstriction; thus, red blood cell (RBC) deformability and stability of hematological parameters might be of particular importance, because alterations during hypoxia might further influence circulation. This study aimed to measure respective parameters in patients with Fontan circulation exposed to normobaric hypoxia. A total of 18 patients with Fontan circulation (16 to 38 years) were exposed to normobaric hypoxia (15.2% ambient oxygen). Blood samples were taken in normoxia, after 24 h in hypoxia, and 60 min after return to normoxia. Blood count, RBC age distribution, EPO, RBC deformability, marker of RBC nitric oxide, oxidative state, and RBC ATP were measured. Hypoxia increased oxidative stress in RBC, but without affecting RBC deformability. RBC age distribution remained unaffected, although EPO concentrations increased, followed by a rise in reticulocyte count at an already high hematocrit. NO metabolism was not affected by hypoxia. Modest normobaric hypoxia for 24 h did not impair RBC deformability in patients with Fontan circulation; however, the oxidative system seemed to be stressed. Given the high baseline Hct in these patients, hypoxia-induced erythropoiesis could adversely affect rheology with more prolonged hypoxia exposure.

Effects of short-term hypercaloric nutrition on orthostatic tolerance in healthy individuals: a randomized controlled crossover study.

Reduced-caloric intake lowers blood pressure through sympathetic inhibition, and worsens orthostatic tolerance within days. Conversely, hypercaloric nutrition augments sympathetic activity and blood pressure. Because dietary interventions could be applied in patients with syncope, we tested the hypothesis that short-term hypercaloric dieting improves orthostatic tolerance. In a randomized crossover trial, 20 healthy individuals (7 women, 26.7 ± 8 years, 22.6 ± 2 kg/m2) followed a 4-day hypercaloric (25% increase of energy intake by fat) or normocaloric nutritional plan, with a washout period of at least 23 days between interventions. We then performed head-up tilt table testing with incremental lower body negative pressure while recording beat-by-beat blood pressure and heart rate. The primary endpoint was orthostatic tolerance defined as time to presyncope. Time to presyncope during combined head-up tilt and lower body negative pressure did not differ between hypercaloric and normocaloric dieting (median 23.19 versus 23.04 min, ratio of median 1.01, 95% CI of ratio 0.5-1.9). Heart rate, blood pressure, heart rate variability, and blood pressure variability in the supine position and during orthostatic testing did not differ between interventions. We conclude that 4 days of moderate hypercaloric nutrition does not significantly improve orthostatic tolerance in healthy individuals. Nevertheless, given the important interaction between energy balance and cardiovascular autonomic control in the brain, caloric intake deserves more attention as a potential contributor and treatment target for orthostatic intolerance.

Real-Time Magnetic Resonance Imaging to Study Orthostatic Intolerance Mechanisms in Human Beings: Proof of Concept.

Background Discerning the mechanisms driving orthostatic symptoms in human beings remains challenging. Therefore, we developed a novel approach combining cardiac and cerebral real-time magnetic resonance imaging, beat-to-beat physiological monitoring, and orthostatic stress testing through lower-body negative pressure (LBNP). We conducted a proof-of-concept study in a patient with severe orthostatic hypotension. Methods and Results We included a 46-year-old man with pure autonomic failure. Without and during -30 mmHg LBNP, we obtained 3T real-time magnetic resonance imaging of the cardiac short axis and quantitative flow measurements in the pulmonary trunk and middle cerebral artery. Blood pressure was 118/74 mmHg during supine rest and 58/35 mmHg with LBNP. With LBNP, left ventricular stroke volume decreased by 44.6%, absolute middle cerebral artery flow by 37.6%, and pulmonary trunk flow by 40%. Conclusions Combination of real-time magnetic resonance imaging, LBNP, and continuous blood pressure monitoring provides a promising new approach to study orthostatic intolerance mechanisms in human beings.

Cardiovascular deconditioning and impact of artificial gravity during 60-day head-down bed rest-Insights from 4D flow cardiac MRI.

Microgravity has deleterious effects on the cardiovascular system. We evaluated some parameters of blood flow and vascular stiffness during 60 days of simulated microgravity in head-down tilt (HDT) bed rest. We also tested the hypothesis that daily exposure to 30 min of artificial gravity (1 g) would mitigate these adaptations. 24 healthy subjects (8 women) were evenly distributed in three groups: continuous artificial gravity, intermittent artificial gravity, or control. 4D flow cardiac MRI was acquired in horizontal position before (-9 days), during (5, 21, and 56 days), and after (+4 days) the HDT period. The false discovery rate was set at 0.05. The results are presented as median (first quartile; third quartile). No group or group × time differences were observed so the groups were combined. At the end of the HDT phase, we reported a decrease in the stroke volume allocated to the lower body (-30% [-35%; -22%]) and the upper body (-20% [-30%; +11%]), but in different proportions, reflected by an increased share of blood flow towards the upper body. The aortic pulse wave velocity increased (+16% [+9%; +25%]), and so did other markers of arterial stiffness ( C A V I ; C A V I 0 ). In males, the time-averaged wall shear stress decreased (-13% [-17%; -5%]) and the relative residence time increased (+14% [+5%; +21%]), while these changes were not observed among females. Most of these parameters tended to or returned to baseline after 4 days of recovery. The effects of the artificial gravity countermeasure were not visible. We recommend increasing the load factor, the time of exposure, or combining it with physical exercise. The changes in blood flow confirmed the different adaptations occurring in the upper and lower body, with a larger share of blood volume dedicated to the upper body during (simulated) microgravity. The aorta appeared stiffer during the HDT phase, however all the changes remained subclinical and probably the sole consequence of reversible functional changes caused by reduced blood flow. Interestingly, some wall shear stress markers were more stable in females than in males. No permanent cardiovascular adaptations following 60 days of HDT bed rest were observed.

Integrative physiological study of adaptations induced by aerobic physical training in hypertensive hearts.

Aerobic physical training reduces arterial pressure in patients with hypertension owing to integrative systemic adaptations. One of the key factors is the decrease in cardiac sympathetic influence. Thus, we hypothesized that among other causes, cardiac sympathetic influence reduction might be associated with intrinsic cardiac adaptations that provide greater efficiency. Therefore, 14 spontaneously hypertensive rats (SHR group) and 14 normotensive Wistar Kyoto rats (WKY group) were used in this study. Half of the rats in each group were trained to swim for 12 weeks. All animals underwent the following experimental protocols: double blockade of cardiac autonomic receptors with atropine and propranolol; echocardiography; and analysis of coronary bed reactivity and left ventricle contractility using the Langendorff technique. The untrained SHR group had a higher sympathetic tone, cardiac hypertrophy, and reduced ejection fraction compared with the untrained WKY group. In addition, reduced coronary bed reactivity due to increased flow, and less ventricular contractile response to dobutamine and salbutamol administration were observed. The trained SHR group showed fewer differences in echocardiographic parameters as the untrained SHR group. However, the trained SHR group showed a reduction in the cardiac sympathetic influence, greater coronary bed reactivity, and increased left intraventricular pressure. In conclusion, aerobic physical training seems to reduce cardiac sympathetic influence and increase contractile strength in SHR rats, besides the minimal effects on cardiac morphology. This reduction suggests intrinsic cardiac adaptations resulting in beneficial adjustments of coronary bed reactivity associated with greater left ventricular contraction.