Closed-loop baroreflex model with biophysically detailed afferent pathway.

In this work, we couple a lumped-parameter closed-loop model of the cardiovascular system with a physiologically-detailed mathematical description of the baroreflex afferent pathway. The model features a classical Hodgkin-Huxley current-type model for the baroreflex afferent limb (primary neuron) and for the second-order neuron in the central nervous system. The pulsatile arterial wall distension triggers a frequency-modulated sequence of action potentials at the afferent neuron. This signal is then integrated at the brainstem neuron model. The efferent limb, representing the sympathetic and parasympathetic nervous system, is described as a transfer function acting on heart and blood vessel model parameters in order to control arterial pressure. Three in silico experiments are shown here: a step increase in the aortic pressure to evaluate the functionality of the reflex arch, a hemorrhagic episode and an infusion simulation. Through this model, it is possible to study the biophysical dynamics of the ionic currents proposed for the afferent limb components of the baroreflex during the cardiac cycle, and the way in which currents dynamics affect the cardiovascular function. Moreover, this system can be further developed to study in detail each baroreflex loop component, helping to unveil the mechanisms involved in the cardiovascular afferent information processing.

Recovery of the baroreflex and autonomic modulation after anesthesia with MS-222 in bullfrogs.

The time course for recovery after anesthesia is poorly described for tricaine methanesulfonate (MS-222). We suggest that the baroreflex and the heart rate variability (HRV) could be used to index the recovery of the autonomic modulation after anesthesia. We analyzed the recovery profile of behavioral and physiological parameters over time to analyze the progression of recovery after anesthesia of American bullfrogs with MS-222. Mean heart rate stabilized after 17 h, whereas the baroreflex efficiency index took 23 h and the baroreflex operating gain, 29 h. Mean arterial pressure recovered after 26 h. Power spectral density peaked at 23 h and again after 40 h. Baroreflex was a relevant component of the first phase of HRV, while autonomic modulation for resting may take longer than 40 h. We suggest that physiological recovery is a complex phenomenon with multiple progressive phases, and the baroreflex may be a useful tool to observe the first substantial recovery of post-instrumentation capacity for autonomic modulation.

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.

Central and peripheral mechanisms underlying postexercise hypotension: a scoping review.

Blood pressure (BP) reduction occurs after a single bout of exercise, referred to as postexercise hypotension (PEH). The clinical importance of PEH has been advocated owing to its potential contribution to chronic BP lowering, and as a predictor of responders to exercise training as an antihypertensive therapy. However, the mechanisms underlying PEH have not been well defined. This study undertook a scoping review of research on PEH mechanisms, as disclosed in literature reviews. We searched the PubMed, Web of Science, Scopus, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, and Sport Discus databases until January 2023 to locate 21 reviews - 13 narrative, four systematic with 102 primary trials, and four meta-analyses with 75 primary trials involving 1566 participants. We classified PEH mechanisms according to major physiological systems, as central (autonomic nervous system, baroreflex, cardiac) or peripheral (vascular, hemodynamic, humoral, and renal). In general, PEH has been related to changes in autonomic control leading to reduced cardiac output and/or sustained vasodilation. However, the role of autonomic control in eliciting PEH has been challenged in favor of local vasodilator factors. The contribution of secondary physiological outcomes to changes in cardiac output and/or vascular resistance during PEH remains unclear, especially by exercise modality and population (normal vs. elevated BP, young vs. older adults). Further research adopting integrated approaches to investigate the potential mechanisms of PEH is warranted, particularly when the magnitude and duration of BP reductions are clinically relevant. (PROSPERO CRD42021256569).

Evening but not morning aerobic training improves sympathetic activity and baroreflex sensitivity in elderly patients with treated hypertension.

The blood pressure-lowering effect of aerobic training is preceded by improving cardiovascular autonomic control. We previously demonstrated that aerobic training conducted in the evening (ET) induces a greater decrease in blood pressure than morning training (MT). To study whether the greater blood pressure decrease after ET occurs through better cardiovascular autonomic regulation, this study aimed to compare MT versus ET on muscle sympathetic nerve activity (MSNA) and baroreflex sensitivity (BRS) in treated patients with hypertension. Elderly patients treated for hypertension were randomly allocated into MT (n = 12, 07.00-10.00 h) or ET (n = 11, 17.00-20.00 h) groups. Both groups trained for 10 weeks, 3 times/week, cycling for 45 min at moderate intensity. Beat-to-beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and MSNA (microneurography) were assessed at the initial and final phases of the study at baseline and during sequential bolus infusions of sodium nitroprusside and phenylephrine (modified-Oxford technique) to evaluate cardiac and sympathetic BRS. Mean blood pressure decreased significantly after ET but not after MT (-9 ± 11 vs. -1 ± 8 mmHg, P = 0.042). MSNA decreased significantly only after ET with no change after MT (-12 ± 5 vs. -3 ± 7 bursts/100 heart beats, P = 0.013). Sympathetic BRS improved after ET but not after MT (-0.8 ± 0.7 vs. 0.0 ± 0.8 bursts/100 heart beats/mmHg, P = 0.052). Cardiac BRS improved similarly in both groups (ET: +1.7 ± 1.8 vs. MT: +1.4 ± 1.9 ms/mmHg, Pphase  ≤ 0.001). In elderly patients treated for hypertension, only ET decreased mean blood pressure and MSNA and improved sympathetic BRS. These findings revealed that the sympathetic nervous system has a key role in ET's superiority to MT in blood pressure-lowering effect. KEY POINTS: Reducing muscle nerve sympathetic activity and increasing sympathetic baroreflex sensitivity plays a key role in promoting the greater blood pressure reduction observed with evening training. These findings indicated that simply changing the timing of exercise training may offer additional benefits beyond antihypertensive medications, such as protection against sympathetic overdrive and loss of baroreflex sensitivity, independent markers of mortality. Our new findings also suggest new avenues of investigation, such as the possibility that evening aerobic training may be beneficial in other clinical conditions with sympathetic overdrive, such as congestive heart failure and hypertrophic cardiomyopathy.

Exercise-induced neuroplasticity in autonomic nuclei restores the cardiac vagal tone and baroreflex dysfunction in aged hypertensive rats.

Aging is accompanied by considerable deterioration of homeostatic systems, such as autonomic imbalance characterized by heightened sympathetic activity, lower parasympathetic tone, and depressed heart rate (HR) variability, which are aggravated by hypertension. Here, we hypothesized that these age-related deficits in aged hypertensive rats can be ameliorated by exercise training, with benefits to the cardiovascular system. Therefore, male 22-mo-old spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto (WKY) submitted to moderate-intensity exercise training (T) or kept sedentary (S) for 8 wk were evaluated for hemodynamic/autonomic parameters, baroreflex sensitivity, cardiac sympathetic/parasympathetic tone and analysis of dopamine ß-hydroxylase (DBH+) and oxytocin (OT+) pathways of autonomic brain nuclei. Aged SHR-S versus WKY-S exhibited elevated mean arterial pressure (MAP: +51%) and HR (+20%), augmented pressure/HR variability, no cardiac vagal tone, and depressed reflex control of the heart (HR range, -28%; gain, -49%). SHR-T exhibited a lower resting HR, a partial reduction in the MAP (-14%), in the pressure/HR variabilities, and restored parasympathetic modulation, with improvement of baroreceptor reflex control when compared with SHR-S. Exercise training increased the ascending DBH+ projections conveying peripheral information to the paraventricular nucleus of hypothalamus (PVN), augmented the expression of OT+ neurons, and reduced the density of DBH+ neurons in the rostral ventrolateral medulla (RVLM) of SHR-T. Data indicate that exercise training induces beneficial neuroplasticity in brain autonomic circuitry, and it is highly effective to restore the parasympathetic tone, and attenuation of age-related autonomic imbalance and baroreflex dysfunction, thus conferring long-term benefits for cardiovascular control in aged hypertensive individuals.NEW & NOTEWORTHY Exercise training reduces high blood pressure and cardiovascular autonomic modulation in aged hypertensive rats. The dysfunction in the baroreflex sensitivity and impaired parasympathetic tone to the heart of aged hypertensive rats are restored by exercise training. Exercise induces beneficial neuroplasticity in the brain nuclei involved with autonomic control of cardiovascular function of aged hypertensive rats.

Concurrent exercise training induces additional benefits to hydrochlorothiazide: Evidence for an improvement of autonomic control and oxidative stress in a model of hypertension and postmenopause.

OBJECTIVE: This study aimed to evaluate whether exercise training could contribute to a better modulation of the neurohumoral mechanisms linked to the pathophysiology of arterial hypertension (AH) in postmenopausal hypertensive rats treated with hydrochlorothiazide (HCTZ). METHODS: Female spontaneously hypertensive rats (SHR) (150-200g, 90 days old) were distributed into 5 hypertensive groups (n = 7-8 rats/group): control (C), ovariectomized (O), ovariectomized treated with HCTZ (OH), ovariectomized submitted to exercise training (OT) and ovariectomized submitted to exercise training and treated with HCTZ (OTH). Ovarian hormone deprivation was performed through bilateral ovariectomy. HCTZ (30mg/kg/day) and concurrent exercise training (3d/wk) were conducted lasted 8 weeks. Arterial pressure (AP) was directly recorded. Cardiac effort was evaluated using the rate-pressure product (RPP = systolic AP x heart rate). Vasopressin V1 receptor antagonist, losartan and hexamethonium were sequentially injected to evaluate the vasopressor systems. Inflammation and oxidative stress were evaluated in cardiac tissue. RESULTS: In addition to the reduction in AP, trained groups improved RPP, AP variability, bradycardic (OT: -1.3 ± 0.4 and OTH: -1.6 ± 0.3 vs. O: -0.6 ± 0.3 bpm/mmHg) and tachycardic responses of baroreflex sensitivity (OT: -2.4 ± 0.8 and OTH: -2.4 ± 0.8 vs. O: -1.3 ± 0.5 bpm/mmHg), NADPH oxidase and IL-10/TNF-α ratio. Hexamethonium injection revealed reduced sympathetic contribution on basal AP in OTH group (OTH: -49.8 ± 12.4 vs. O: -74.6 ± 18.1 mmHg). Furthermore, cardiac sympathovagal balance (LF/HF ratio), IL-10 and antioxidant enzymes were enhanced in OTH group. AP variability and baroreflex sensitivity were correlated with systolic AP, RPP, LF/HF ratio and inflammatory and oxidative stress parameters. CONCLUSION: The combination of HCTZ plus concurrent exercise training induced additional positive adaptations in cardiovascular autonomic control, inflammation and redox balance in ovariectomized SHR. Therefore, combining exercise and medication may represent a promising strategy for managing classic and remaining cardiovascular risks in AH.

A comparison of four common mathematical models to assess baroreflex sensitivity.

Different methods have been used to assess baroreflex gain in experiments where changes in the carotid sinus pressure or the arterial blood pressure using different techniques provoke a baroreflex response, usually a rapid variation of heart rate. Four mathematical models are most used in the literature: the linear regression, the piecewise regression, and two different four-parameter logistic equations: equation 1, Y = (A1-D1)/[1 + eB1(X - C1) ] + D1; equation 2, Y = (A2-D2)/[1 + (X/C2)B2 ] + D2. We compared the four models regarding the best fit to previously published data in all vertebrate classes. The linear regression had the worst fit in all cases. The piecewise regression generally exhibited a better fit than the linear regression, though it returned a similar fit when no breakpoints were found. The logistic equations showed the best fit among the tested models and were similar to each other. We demonstrate that equation 2 is asymmetric and the level of asymmetry is accentuated according to B2. This means that the baroreflex gain calculated when X = C2 is different from the actual maximum gain. Alternatively, the symmetric equation 1 returns the maximum gain when X = C1. Furthermore, the calculation of baroreflex gain using equation 2 disregards that baroreceptors may reset when individuals experience different mean arterial pressures. Finally, the asymmetry from equation 2 is a mathematical artifact inherently skewed to the left of C2, thus bearing no biological meaning. Therefore, we suggest that equation 1 should be used instead of equation 2.

Food readjustment plus exercise training improves cardiovascular autonomic control and baroreflex sensitivity in high-fat diet-fed ovariectomized mice.

Despite consensus on the benefits of food readjustment and/or moderate-intensity continuous exercise in the treatment of cardiometabolic risk factors, there is little evidence of the association between these two cardiovascular risk management strategies after menopause. Thus, the objective of this study was to evaluate the effects of food readjustment and/or exercise training on metabolic, hemodynamic, autonomic, and inflammatory parameters in a model of loss of ovarian function with diet-induced obesity. Forty C57BL/6J ovariectomized mice were divided into the following groups: high-fat diet-fed - 60% lipids throughout the protocol (HF), food readjustment - 60% lipids for 5 weeks, readjusted to 10% for the next 5 weeks (FR), high-fat diet-fed undergoing moderate-intensity exercise training (HFT), and food readjustment associated with moderate-intensity exercise training (FRT). Blood glucose evaluations and oral glucose tolerance tests were performed. Blood pressure was assessed by direct intra-arterial measurement. Baroreflex sensitivity was tested using heart rate phenylephrine and sodium nitroprusside induced blood pressure changes. Cardiovascular autonomic modulation was evaluated in time and frequency domains. Inflammatory profile was evaluated by IL-6, IL-10 cytokines, and TNF-alpha measurements. Only the exercise training associated with food readjustment strategy induced improved functional capacity, body composition, metabolic parameters, inflammatory profile, and resting bradycardia, while positively changing cardiovascular autonomic modulation and increasing baroreflex sensitivity. Our findings demonstrate that the association of these strategies seems to be effective in the management of cardiometabolic risk in a model of loss of ovarian function with diet-induced obesity.

Vulnerability and resilience to cardiovascular and neuroendocrine effects of stress in adult rats with historical of chronic stress during adolescence.

AIMS: This study investigated the influence of exposure to stress during adolescence in autonomic, cardiovascular, neuroendocrine and somatic changes evoked by chronic stress in adult rats. MAIN METHODS: Animals were subjected to a 10-days protocol of repeated restraint stress (RRS, habituating) or chronic variable stress (CVS, non-habituating) during adolescence, adulthood, or repeated exposure to either RRS or CVS in adolescence and adulthood (adolescence+adulthood group). The trials to measure autonomic, cardiovascular, neuroendocrine and somatic changes in all experimental groups were performed in adulthood. KEY FINDINGS: CVS increased basal circulating corticosterone levels and caused adrenal hypertrophy in the adolescence+adulthood group, an effect not identified in animals subjected to this stressor only in adulthood or adolescence. CVS also caused a sympathetically-mediated resting tachycardia in the adulthood group. This effect of CVS was not identified in the adolescence+adulthood group once the increased cardiac sympathetic activity was buffered by a decrease in intrinsic heart rate in these animals. Moreover, the impairment in baroreflex function observed in the adulthood group subjected to CVS was shifted to an improvement in animals subjected to repeated exposure to this stressor during adolescence and adulthood. The RRS in the adolescence+adulthood group caused a sympathetically-mediated resting tachycardia, which was not observed in the adulthood group. SIGNIFICANCE: Our findings suggest that enduring effects of adverse events during adolescence included a vulnerability to neuroendocrine changes and a resilience to autonomic and cardiovascular dysfunctions caused by the CVS. Furthermore, results of RRS indicated a vulnerability to cardiovascular and autonomic changes evoked by homotypic stressors.

The medial prefrontal cortex and the cardiac baroreflex activity: physiological and pathological implications.

The cardiac baroreflex is an autonomic neural mechanism involved in the modulation of the cardiovascular system. It influences the heart rate and peripheral vascular resistance to preserve arterial blood pressure within a narrow variation range. This mechanism is mainly controlled by medullary nuclei located in the brain stem. However, supramedullary areas, such as the ventral portion of medial prefrontal cortex (vMPFC), are also involved. Particularly, the glutamatergic NMDA/NO pathway in the vMPFC can facilitate baroreflex bradycardic and tachycardic responses. In addition, cannabinoid receptors in this same area can reduce or increase those cardiac responses, possibly through alteration in glutamate release. This vMPFC network has been associated to cardiovascular responses during stressful situations. Recent results showed an involvement of glutamatergic, nitrergic, and endocannabinoid systems in the blood pressure and heart rate increases in animals after aversive conditioning. Consequently, baroreflex could be modified by the vMPFC neurotransmission during stressful situations, allowing necessary cardiovascular adjustments. Remarkably, some mental, neurological and neurodegenerative disorders can involve damage in the vMPFC, such as posttraumatic stress disorder, major depressive disorder, Alzheimer's disease, and neuropathic pain. These pathologies are also associated with alterations in glutamate/NO release and endocannabinoid functions along with baroreflex impairment. Thus, the vMPFC seems to play a crucial role on the baroreflex control, either during pathological or physiological stress-related responses. The study of baroreflex mechanism under such pathological view may be helpful to establish causality mechanisms for the autonomic and cardiovascular imbalance found in those conditions. It can explain in the future the reasons of the high cardiovascular risk some neurological and neurodegenerative disease patients undergo. Additionally, the present work offers insights on the possible contributions of vMPFC dysfunction on baroreflex alterations, which, in turn, may raise questions in what extent other brain areas may play a role in autonomic deregulation under such pathological situations.

Cardiovascular autonomic modulation during passive heating protocols: a systematic review.

Objective.To conduct a systematic review of the possible effects of passive heating protocols on cardiovascular autonomic control in healthy individuals.Approach.The studies were obtained from MEDLINE (PubMed), LILACS (BVS), EUROPE PMC (PMC), and SCOPUS databases, simultaneously. Studies were considered eligible if they employed passive heating protocols and investigated cardiovascular autonomic control by spontaneous methods, such as heart rate variability (HRV), systolic blood pressure variability (SBPV), and baroreflex sensitivity (BRS), in healthy adults. The revised Cochrane risk-of-bias tool (RoB-2) was used to assess the risk of bias in each study.Main results.Twenty-seven studies were included in the qualitative synthesis. Whole-body heating protocols caused a reduction in cardiac vagal modulation in 14 studies, and two studies reported both increased sympathetic modulation and vagal withdrawal. Contrariwise, local-heating protocols and sauna bathing seem to increase cardiac vagal modulation. A reduction of BRS was reported in most of the studies that used whole-body heating protocols. However, heating effects on BRS remain controversial due to methodological differences among baroreflex analysis and heating protocols.Significance.Whole-body heat stress may increase sympathetic and reduce vagal modulation to the heart in healthy adults. On the other hand, local-heating therapy and sauna bathing seem to increase cardiac vagal modulation, opposing sympathetic modulation. Nonetheless, further studies should investigate acute and chronic effects of thermal therapy on cardiovascular autonomic control.

Ontogenetic scaling of the baroreflex function in the green iguana (Iguana iguana).

Large body mass (Mb) in vertebrates is associated with longer pulse intervals between heartbeats (PI) and thicker arterial walls. Longer PI increases the time for diastolic pressure decay, possibly resulting in loss of cardiac energy as "oscillatory power," whereas thicker arterial walls may affect the transmission of impulses and sensing of pressure fluctuations thus impairing baroreflex function. We aimed to investigate the effect of growth on the relative cardiac energy loss and baroreflex function. We predicted that 1) the relative use of cardiac energy should be preserved with increased time constant for pressure decay (τ = vascular resistance × compliance) and 2) if arterial circumferential distensibility does not change, baroreflex function should be unaltered with Mb. To test these hypotheses, we used green iguanas (Iguana iguana) weighing from 0.03 to 1.34 kg (43-fold increment in Mb). PI (P = 0.037) and τ (P = 0.035) increased with Mb, whereas the oscillatory power fraction (P = 0.245) was unrelated to it. Thus, the concomitant alterations of τ and PI allowed the conservation of cardiac energy in larger lizards. Larger animals had thicker arterial walls (P = 0.0007) and greater relative collagen content (P = 0.022). Area compliance scaled positively to Mb (P = 0.045), though circumferential distensibility (P = 0.155) and elastic modulus (P = 0.762) were unaltered. In addition, baroreflex sensitivity, measured by both the pharmacological (P = 0.152) and sequence methods (P = 0.088), and the baroreflex effectiveness index (P = 0.306) were also unrelated to Mb. Therefore, changes in arterial morphology did not affect circumferential distensibility and presumably sensing of pressure fluctuation, and the cardiovagal baroreflex is preserved across different Mb.

Intracranial compliance in type 2 diabetes mellitus and its relationship with the cardiovascular autonomic nervous control.

The intracranial compliance in type 2 diabetes mellitus (T2DM) patients and the association with cardiovascular autonomic control have not been fully elucidated. The aim of this study was to assess intracranial compliance using the noninvasive intracranial pressure (niICP) and the monitoring of waveform peaks (P1, P2, and P3) and the relationship with cardiovascular autonomic control in T2DM patients. Thirty-two men aged 40-60 years without cardiovascular autonomic neuropathy (CAN) were studied: T2DMG (n=16) and control group CG (n=16). The niICP was evaluated by a noninvasive extracranial sensor placed on the scalp. Cardiovascular autonomic control was evaluated by indices of the baroreflex sensitivity (BRS), from temporal series of R-R intervals of electrocardiogram and systolic arterial pressure, during supine and orthostatic positions. The participants remained in the supine position for 15 min and then 15 min more in orthostatism. T2DMG presented a decrease of the P2/P1 ratio during the orthostatic position (P<0.001). There was a negative moderate correlation between the P2 peak with cardiovascular coupling (K2HP-SAPLF) in supine (r=-0.612, P=0.011) and orthostatic (r=-0.568, P=0.020) positions in T2DMG. We concluded that T2DM patients without CAN and cardiovascular complications presented intracranial compliance similar to healthy subjects. Despite preserved intracranial adjustments, T2DM patients had a response of greater magnitude in orthostatism. In addition, the decoupling between the heart period and blood pressure signal oscillations in low frequency appeared to be related to the worsening of intracranial compliance due to the increased P2 peak.

Role of aerobic physical training on cardiac autonomic and morphophysiological dysfunction in hypertensive rats subjected to ovarian hormone deprivation.

Here we investigated the effects of physical training on cardiovascular autonomic control and cardiac morphofunctional parameters in spontaneously hypertensive rats (SHRs) subjected to ovarian hormone deprivation. Forty-eight 10-week-old SHRs were divided into two groups: ovariectomized (OVX, n=24) and sham (SHAM, n=24). Half of each group (n=12) was trained by swimming for 12 weeks (OVX-T and SHAM-T). Cardiac morphology and functionality were assessed using echocardiography, and autonomic parameters were assessed using double pharmacological autonomic block, baroreflex sensitivity (BRS), and analyses of heart rate variability (HRV) and blood pressure variability (BPV). Ovariectomy did not influence the cardiac autonomic tonus balance unlike physical training, which favored greater participation of the vagal autonomic tonus. Ovariectomy and aerobic physical training did not modify HRV and BRS, unlike BPV, for which both methods reduced low-frequency oscillations, suggesting a reduction in sympathetic vascular modulation. Untrained ovariectomized animals showed a reduced relative wall thickness (RWT) and increased diastolic and systolic volumes and left ventricular diameters, resulting in increased stroke volume. Trained ovariectomized animals presented reduced posterior wall thickness and RWT as well as increased final diastolic diameter, left ventricular mass, and stroke volume. Ovarian hormone deprivation in SHRs promoted morphofunctional adaptations but did not alter the evaluation of cardiac autonomic parameters. In turn, aerobic physical training contributed to a more favorable cardiac autonomic balance to the vagal autonomic component and promoted morphological adaptations but had little effect on cardiac functionality.

Combined effects of angiotensin receptor blocker use and physical training in hypertensive men.

PURPOSE: Pharmacological (angiotensin II receptor type 1 receptor blocker use) and non-pharmacological treatment (physical aerobic exercise) are important strategies to reduces blood pressure and control arterial hypertension; however, only few clinical studies have evaluated their combined effects on autonomic cardiovascular control. Therefore, we investigated the effect of a combination intervention that involved losartan administration and physical aerobic training on autonomic cardiovascular control. METHODS: Thirty-two men (aged 40 to 60 years) were assigned into two groups: normotensive group, without any pharmacological treatment (NG, N = 16), or hypertensive group, with losartan administration (HG, N = 16). They underwent a physical aerobic training for 16 weeks, thrice a week. Hemodynamic parameters, heart rate variability (HRV), blood pressure variability, and spontaneous baroreflex sensitivity (BRS) were measured before and after training. RESULTS: Before training, both the groups showed similar values of hemodynamic parameters. However, the HG showed decreased BRS and HRV, characterized by reduction in sympathetic (p = .02) and vagal (p < .001) modulation. After training, the NG exhibited decreased heart rate (HR) at rest (p < .001), whereas the HG showed decreased HR at rest (p < .001) and blood pressure (BP) (p = .001). The HG showed decreased sympathetic modulation (p = .02) and increased BRS (p < .001) and vagal modulation (p < .001), but HRV (p < .001) and BRS gain (p < .001) remained significantly lower when compared to the NG. CONCLUSIONS: Physical aerobic training was essential to improve the BRS and HRV cardiac autonomic modulation in the HG. However, it was not sufficient to normalize the analyzed autonomic parameters.

Impairment on Cardiovascular Autonomic Modulation in Women with Migraine.

Autonomic dysfunction, such as reduced vagally mediated heart rate variability, has been suggested in headache patients but is still uncertain when considering primary headache disorders. This study aims to compare the heart rate and blood pressure variability and baroreflex sensitivity between women with migraine and controls. A migraine (n = 20) and a control group (n = 20) of age-matched women without headache were evaluated. Heart rate variability was analyzed through frequency-domain using spectral analysis presenting variance, low-frequency (LF; 0.04-0.15 Hz) and high-frequency (HF; 0.15-0.4 Hz) bands and by time domain (root mean square of successive R-R interval differences, RMSSD). Blood pressure variability was analyzed with spectral analysis and baroreflex sensitivity with the sequence method. Migraine group had lower heart rate variability characterized by a reduction in total variance, LF oscillations (sympathetic/vagal modulation) and HF oscillations (vagal modulation), and a reduction in SD and RMSSD compared to control group. No difference was found in the blood pressure variability analysis. Regarding baroreflex sensitivity, migraine group had decreased values of total gain, gain down and up compared to control group. Women with migraine exhibited autonomic modulation alterations, expressed by decreased values of heart rate variability and baroreflex sensitivity, but not by differences in blood pressure variability.

Baroreflex Sensitivity Assessment Using the Sequence Method with Delayed Signals in End-Stage Renal Disease Patients.

Impaired baroreflex sensitivity (BRS) is partially responsible for erratic blood pressure fluctuations in End-Stage Renal Disease (ESRD) patients on chronic hemodialysis (HD), which is related to autonomic nervous dysfunction. The sequence method with delayed signals allows for the measurement of BRS in a non-invasive fashion and the investigation of alterations in this physiological feedback system that maintains BP within healthy limits. Our objective was to evaluate the modified delayed signals in the sequence method for BRS assessment in ESRD patients without pharmacological antihypertensive treatment and compare them with those of healthy subjects. We recruited 22 healthy volunteers and 18 patients with ESRD. We recorded continuous BP to obtain a 15-min time series of systolic blood pressure and interbeat intervals during the supine position (SP) and active standing (AS) position. The time series with delays from 0 to 5 heartbeats were used to calculate the BRS, number of data points, number of sequences, and estimation error. The BRS from the ESRD patients was smaller than in healthy subjects (p < 0.05). The BRS estimation with the delayed sequences also increased the number of data points and sequences and decreased the estimation error compared to the original time series. The modified sequence method with delayed signals may be useful for the measurement of baroreflex sensitivity in ESRD patients with a shorter recording time and maintaining an estimation error below 0.01 in both the supine and active standing positions. With this framework, it was corroborated that baroreflex sensitivity in ESRD is decreased when compared with healthy subjects.

Acute autonomic effects of rose oxide on cardiovascular parameters of Wistar and spontaneously hypertensive rats.

AIMS: Anti-inflammatory molecules, such as rose oxide (RO), are likely to exert therapeutic effects in systemic arterial hypertension (SAH), a disease associated with abnormal immune responses. We aimed to investigate acute autonomic effects of RO on hemodynamic parameters of Wistar and spontaneously hypertensive rats (SHR). METHODS: Rats were anesthetized and femoral artery and veins were cannulated. Next day, blood pressure (BP) and heart rate (HR) were recorded. Acute effects of RO (1.25, 2.5, or 5.0 mg/kg; iv) on BP, HR, and variability of systolic arterial pressure (SAP) and pulse interval (PI) were assessed. The effects of RO were also investigated in SHR, which received atropine (2 mg/kg), propranolol (4 mg/kg), or hexamethonium (20 mg/kg) 15 min before receiving RO. Vasorelaxant effects of RO (10-10 to 10-4 M) on aortic rings of rats were also assessed. KEY FINDINGS: In Wistar rats, none of the RO doses evoked significant changes in BP, HR, and variability of SAP and PI. On the other hand, in SHR, RO elicited reduction in mean arterial pressure (MAP), and prevented the increase in the low frequency power (LF) of the SAP spectra. Pretreatment with atropine or propranolol did not alter hypotension, but attenuated RO-induced bradycardia. Hexamethonium prevented RO-induced hypotension and bradycardia. RO exerted vasorelaxant effects on aortic rings with (Wistar and SHR) or without functional endothelium (SHR only). SIGNIFICANCE: Rose oxide, a monoterpene with anti-inflammatory properties, acts as an antihypertensive molecule due to its ability to acutely promote hypotension and bradycardia in spontaneously hypertensive rats.

Nicotinamide attenuates streptozotocin-induced diabetes complications and increases survival rate in rats: role of autonomic nervous system.

BACKGROUND: To evaluate the effect of nicotinamide prior to streptozotocin-induced (STZ) diabetes in baroreflex sensitivity and cardiovascular autonomic modulation, and its association with hemodynamics and metabolic parameters. METHODS: Methods: Male Wistar rats were divided into control (Cont) and STZ-induced diabetes (Diab). Half of the rats from each group received a single dose of nicotinamide (100 mg/Kg) before STZ injection (Cont+NicA and Diab+NicA). All groups were followed-up for 5 weeks. RESULTS: Body weight loss of more than 40% was observed in Diab throughout the period (Diab: 271.00 ± 12.74 g; Diab+NicA: 344.62 ± 17.82). Increased glycemia was seen in Diab rats (541.28 ± 18.68 mg/dl) while Diab+NicA group had a slight decrease (440.87 ± 20.96 mg/dl). However, insulin resistance was observed only in Diab. In relation to Cont, heart rate, mean blood pressure and diastolic function were reduced when compared to Diab, together with parasympathetic modulation and baroreflex sensitivity. All of these parameters were improved in Diab+NicA when compared to Diab. Improved baroreflex sensitivity and parasympathetic modulation were correlated with glycemia, insulin resistance, and body weight mass. Additionally, Diab+NicA group increased survival rate. CONCLUSIONS: Results suggest that the association of nicotinamide in STZ-induced diabetic rats prevents most of the expected derangements mainly by preserving parasympathetic and baroreflex parameters.