Baroreflex Function Research Articles

Efficacy of Paced Breathing at the Low-frequency Peak on Heart Rate Variability and Baroreflex Sensitivity.

We developed a simple method for identifying resonance frequency by focusing on the spectral peak of the low-frequency (LF) component of heart rate variability (HRV) and examined the hypothesis that paced breathing at an accurate resonance frequency increases HRV and baroreflex sensitivity (BRS). We assessed a peak frequency of the LF component of the resting HRV by using power spectral analysis under respiratory control at 0.25Hz, and a resonance frequency, which was evaluated by using the standard breathing maneuver (Lehrer 2007). We examined the effects of paced breathing at the peak frequency of the LF component (Spectral condition) and paced breathing at the resonance frequency as determined by the standard breathing maneuver (Standard condition) on HRV and BRS in 28 healthy college students and young adults. Electrocardiogram, respiration, and noninvasive continuous blood pressure was recorded during a 5-min baseline, followed by a 5-min paced breathing session. Results indicated that the BRS increased during the breathing session under both conditions, but the increase in BRS under the Spectral condition was higher than the Standard condition (p < .05). The LF amplitude increased during the breathing session under both conditions (p < .001), although the difference between the conditions was not significant. These results suggest that paced breathing at the peak frequency of the LF component enhanced the autonomic baroreflex function. Moreover, assessment of the LF-peak may provide more accurate information on resonance frequency for paced breathing during HRV biofeedback.

Effect of Salt Supplementation on Sympathetic Activity and Endothelial Function in Salt-Sensitive Type 2 Diabetes.

Lower sodium intake is paradoxically associated with higher mortality in type 2 diabetes (T2D). To determine whether sympathetic nervous system (SNS) activation and endothelial dysfunction contribute to these observations, we examined the effect of salt supplementation on these systems in people with T2D with habitual low sodium. We hypothesized that salt supplementation would lower SNS activity and improve endothelial function compared to placebo. We conducted a randomized, double-blinded, placebo-controlled crossover trial. The study took place in a tertiary referral diabetes outpatient clinic. Twenty-two people with T2D with habitual low sodium intake (24-hour urine sodium <150 mmol/24h) were included. Salt supplementation (100 mmol NaCl/24h) or placebo for 3 weeks was administered. The primary outcome of SNS activity and endothelial function was assessed as follows: Microneurography assessed muscle sympathetic nerve activity (MSNA), pulse amplitude tonometry assessed endothelial function via reactive hyperemic index (RHI), and arterial stiffness was assessed via augmentation index (AI). Secondary outcomes included cardiac baroreflex, serum aldosterone, ambulatory blood pressure monitoring (ABPM), heart rate variability (HRV), and salt sensitivity. Compared to placebo, salt supplementation increased MSNA (burst frequency P = .047, burst incidence P = .016); however, RHI (P = .24), AI (P = .201), ABPM (systolic P = .09, diastolic P = .14), and HRV were unaffected. Salt supplementation improved baroreflex (slope P = .026) and lowered aldosterone (P = .004), and in salt-resistant individuals there was a trend toward improved RHI (P = .07). In people with T2D and low habitual sodium intake, salt supplementation increased SNS activity without altering endothelial function or blood pressure but improved baroreflex function, a predictor of cardiac mortality. Salt-resistant individuals trended toward improved endothelial function with salt supplementation.

Impaired Baroreflex Function in an Ovine Model of Chronic Heart Failure Induced by Multiple Coronary Microembolizations.

Testing new therapies in heart failure (HF) requires a chronic stable model of HF in large animals. Microembolization of the coronary arteries has been used to model HF previously; however, neural control has not been previously explored in this model. Thus the aim of this study was to further characterize neural control in this model of HF. HF was induced by infusion of microspheres (45 micron; 1.3 ml) into the proximal left coronary artery or left descending coronary arteries, with three sequential embolizations over 3 weeks. Twelve to 14 weeks after the final embolization, and when ejection fraction had decreased below 45%, animals were instrumented to record blood pressure and heart rate. Baroreflex control of heart rate was investigated in conscious animals. Additionally, pressure-volume loops were constructed under anesthesia. Embolization-induced HF was associated with a decrease in mean arterial pressure (67 ± 2 vs. 85 ± 4 mmHg, p < 0.05), an increase in heart rate (108 ± 4 vs. 94 ± 4 bpm, p < 0.05), and a significant increase in left ventricular end-diastolic pressure (11.4 ± 2 vs. 6.2 ± 1 mmHg, p < 0.01). Under conscious conditions, there was a significant decrease in the gain (−8.2 ± 2 vs. −4.1 ± 1 beats/min/mmHg, p < 0.05) as well as the lower plateau of the baroreflex in HF compared to control animals. HF was also associated with significantly increased respiratory rate (107 ± 4 vs. 87 ± 4 breaths/min, p < 0.01) and incidence of apneas (520 ± 24 vs. 191 ± 8 apnea periods >4 s, p < 0.05), compared to control sheep. The microembolization model of heart failure is associated with an increase in left ventricular end-diastolic pressure, impaired cardiac function, and altered baroreflex control of the heart. These findings suggest this chronic model of HF is appropriate to use for investigating interventions aimed at improving neural control in HF.

Role of hippocampal nitrergic neurotransmission in behavioral and cardiovascular dysfunctions evoked by chronic social stress

Increased nitric oxide (NO) levels have been identified in the hippocampus of animals subjected to social isolation. However, a role of this change in behavioral and physiological changes evoked by isolation has never been evaluated. Thus, this study investigated the involvement of nitrergic neurotransmission acting via the neuronal isoform of nitric oxide synthase (nNOS) within the dorsal hippocampus in behavioral and cardiovascular changes in isolated reared rats. For this, male rats were isolated from weaning at 21 days postnatal for 40 days. We identified that social isolation increased hippocampal NO formation and nNOS expression. Besides, anxiogenic- and depressive-like effect identified in isolated animals were not affected by intra-hippocampal microinjection of either the NO scavenger carboxy-PTIO or the selective nNOS inhibitor Nω-Propyl-l-arginine (NPLA). Isolation also increased basal arterial pressure, impaired the baroreflex function and decreased the tachycardia to restraint stress. The effects in restraint-evoked tachycardia were inhibited by hippocampal treatment with either carboxy-PTIO or NPLA. Intra-hippocampal administration of either carboxy-PTIO or NPLA also enhanced the pressor response to restraint in isolated, but not in control animals. Taken together, these findings indicate that increased NO release within the dorsal hippocampus is involved in impairment of cardiovascular responses to a novel stressor, but not in behavioral effects and baroreflex changes, evoked by social isolation. Furthermore, exposure to this stressor evokes the emergence of an inhibitory role of hippocampal nNOS activation in cardiovascular changes to a novel stressor, which might constitute a prominent adaptive response.

Acute effects of resonance frequency breathing on cardiovascular regulation.

Acute slow breathing may have beneficial effects on cardiovascular regulation by affecting hemodynamics and the autonomic nervous system. Whether breathing at the resonance frequency (RF), a breathing rate that maximizes heart rate oscillations, induces differential effects to that of slow breathing is unknown. We compared the acute effects of breathing at either RF and RF + 1 breaths per minute on muscle sympathetic nervous activity (MSNA) and baroreflex function. Ten healthy men underwent MSNA, blood pressure (BP), and heart rate (HR) recordings while breathing for 10 min at their spontaneous breathing (SB) rate followed by 10 min at both RF and RF + 1 randomly assigned and separated by a 10‐min recovery. Breathing at either RF or RF + 1 induced similar changes in HR and HR variability, with increased low frequency and decreased high frequency oscillations (p < .001 for both). Both respiration rates decreased MSNA (−5.6 and −7.3 bursts per min for RF and RF + 1 p < .05), with the sympathetic bursts occurring more often during mid‐inspiration to early expiration (+57% and + 80%) and longer periods of silence between bursts were seen (p < .05 for RF + 1). Systolic BP was decreased only during RF (−4.6 mmHg, p < .05) but the decrease did not differ to that seen during RF + 1 (−3.1 mmHg). The sympathetic baroreflex function remained unchanged at either breathing rates. The slope of the cardiac baroreflex function was unaltered but the cardiac baroreflex efficiency was improved during both RF and RF + 1. Acute breathing at either RF or RF + 1 has similar hemodynamic and sympatho‐inhibitory effects in healthy men.

Sex differences in baroreflex function in health and disease.

This brief review summarizes the current knowledge on sex differences in baroreflex function, with a major focus on studies in humans. It has been demonstrated that healthy women have blunted cardiovagal baroreflx sensitivity during a rapid (i.e., within seconds) hypertensive stimulus, but baroreflex sensitivity is similar between the sexes during a hypotensive stimulus. Normal aging decreases cardiovagal baroreflex sensitivity and the rate of decline is similar in men and women. Cardiovagal baroreflex sensitivity is reduced in pathological conditions such as hypertension and type II diabetes, and the reduction is greater in female patients than male patients. There is no clear sex difference in sympathetic baroreflex sensitivity among young individuals, however, with women of more advanced age, sympathetic baroreflex sensitivity decreases, which appears to be associated with greater arterial stiffness compared with similarly aged men. The blunted sympathetic baroreflex sensitivity in older women may predispose them to an increased prevalence of hypertension and cardiovascular disease.

Short- and long-term effects of maternal dyslipidaemia on blood pressure and baroreflex sensitivity in male rat offspring.

Maternal dyslipidaemia is a predisposing factor for arterial hypertension in male rat offspring at adulthood. This study was designed to investigate the short- and long-term effects of maternal dyslipidaemia on blood pressure (BP) and baroreflex control in male rat offspring. Animals were obtained from mothers who received a dyslipidaemic (DLP, n=7) or control (CTL, n=7) diet during pregnancy and lactation. At 30 and 90days of age, arterial pressure (AP), heart rate (HR) and baroreflex function were evaluated. In addition, spectral analysis of the systolic AP, diastolic AP, mean AP, HR, and spontaneous baroreflex were assessed. Data were expressed as mean±SEM and Student's t-test was used for comparison among groups, with statistical significance considered to be P<.05. At 30days of age, male offspring had similar BP, HR and preserved baroreflex sensitivity. In addition, low frequency (LF) oscillation, high frequency (HF) oscillation and LF/HF ratio of AP and HR were similar in juvenile rats. At 90days of age, male offspring from dyslipidaemic dams had augmented BP (P<.05) when compared to CTL group. Adult male rats from dyslipidaemic dams had a reduction in baroreflex control (P<.05) in comparison to CTL rats. The present study indicates that offspring from dams fed on a dyslipidaemic diet during pregnancy and lactation do not show alteration in blood pressure and baroreflex control in early life, but display a decline in baroreflex control and hypertension in adulthood.

Short-term water deprivation does not increase blood pressure variability or impair neurovascular function in healthy young adults.

High dietary salt increases arterial blood pressure variability (BPV) in salt-resistant, normotensive rodents and is thought to result from elevated plasma [Na+] sensitizing central sympathetic networks. Our purpose was to test the hypothesis that water deprivation (WD)-induced elevations in serum [Na+] augment BPV via changes in baroreflex function and sympathetic vascular transduction in humans. In a randomized crossover fashion, 35 adults [17 female/18 male, age: 25 ± 4 yr, systolic/diastolic blood pressure (BP): 107 ± 11/60 ± 7 mmHg, body mass index: 23 ± 3 kg/m2] completed two hydration protocols: a euhydration control condition (CON) and a stepwise reduction in water intake over 3 days, concluding with 16 h of WD. We assessed blood and urine electrolyte concentrations and osmolality, resting muscle sympathetic nerve activity (MSNA; peroneal microneurography; 18 paired recordings), beat-to-beat BP (photoplethysmography), common femoral artery blood flow (Doppler ultrasound), and heart rate (single-lead ECG). A subset of participants (n = 25) underwent ambulatory BP monitoring during day 3 of each protocol. We calculated average real variability as an index of BPV. WD increased serum [Na+] (141.0 ± 2.3 vs. 142.1 ± 1.7 mmol/L, P < 0.01) and plasma osmolality (288 ± 4 vs. 292 ± 5 mosmol/kg H2O, P < 0.01). However, WD did not increase beat-to-beat (1.9 ± 0.4 vs. 1.8 ± 0.4 mmHg, P = 0.24) or ambulatory daytime (9.6 ± 2.1 vs. 9.4 ± 3.3 mmHg, P = 0.76) systolic BPV. Additionally, sympathetic baroreflex sensitivity (P = 0.20) and sympathetic vascular transduction were not different after WD (P = 0.17 for peak Δmean BP following spontaneous MSNA bursts). These findings suggest that, despite modestly increasing serum [Na+], WD does not affect BPV, arterial baroreflex function, or sympathetic vascular transduction in healthy young adults.

Meeting international aerobic physical activity guidelines is associated with enhanced cardiovagal baroreflex sensitivity in healthy older adults.

Cardiovagal baroreflex sensitivity (cvBRS) reflects the efficiency of modulating heart rate in response to changes in systolic blood pressure. International guidelines recommend that older adults achieve at least 150min of moderate-vigorous physical activity per week. We tested the hypothesis that older adults who achieve these guidelines will exhibit greater cardiovagal baroreflex sensitivity versus those who do not. A cross-sectional comparison of older adults who did (active, 66 ± 5years, 251 ± 79min/week; n = 19) and who did not (inactive, 68 ± 7years, 89 ± 32min/week; n = 17) meet the activity guidelines. Beat-by-beat R-R intervals (electrocardiography) and systolic blood pressure (finger photoplethysmography) were recorded. Spontaneous cardiovagal baroreflex sensitivity was assessed using the sequence technique from 10min of resting supine data. Cardiovagal baroreflex function was also measured during early phaseII and phaseIV of the Valsalva maneuver. Peak oxygen uptake was determined during maximal cycle ergometry. Moderate-vigorous intensityphysicalactivity and time spentsedentary were assessed over 5days using the PiezoRx and activPAL, respectively. Groups had similar peak oxygen uptake (active 25 ± 9 vs. inactive 22 ± 6ml/kg/min; p = 0.218) and sedentary time (active 529 ± 60 vs. inactive 568 ± 88min/day; p = 0.130). However, the active group had greater (all, p < 0.019) cvBRS at rest (9.1 ± 2.7 vs. 5.0 ± 1.9ms/mmHg), during phaseII (8.2 ± 3.8 vs. 5.4 ± 2.1ms/mmHg), and during phaseIV (9.9 ± 3.8 vs. 5.6 ± 1.6ms/mmHg). In the pooled sample, moderate-vigorous physical activity was positively correlated (all, p < 0.015) with spontaneous (R = 0.427), phaseII (R = 0.447), and phaseIV cvBRS (R = 0.629). Independent of aerobic fitness and sedentary time, meeting activity guidelines was associated with superior cardiovagal baroreflex sensitivity at rest and during the Valsalva maneuver in older adults.

P4554Central-acting aminopeptidase a inhibitors for new treatment of hypertension: from discovery to clinical trial

Abstract The hyperactivity of the brain renin–angiotensin system (RAS) has been implicated in the development and maintenance of arterial hypertension (HTA). Our aim was to demonstrate that normalizing brain RAS hyperactivity could constitute a new therapeutic approach for HTA treatment We first demonstrated in the brain that aminopeptidase A (APA) is the enzyme generating angiotensin III (AngIII) from AngII. Then, using the specific and selective APA inhibitor, EC33 ((3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid), we showed that AngIII is one of the main effector peptides of the brain RAS, exerting a tonic stimulatory control over blood pressure (BP) in hypertensive rats. This suggests that brain APA may be a potential therapeutic target for HTA treatment. We then designed RB150 {4,4-dithio[bis(3-aminobutyl sulfonic acid)]}, an orally active prodrug of EC33. RB150, given orally in conscious deoxycorticosterone acetate-salt (DOCA-salt) rats or spontaneously hypertensive rats, crosses the intestinal, hepatic and blood-brain barriers, enters the brain, where it is cleaved by brain reductases, generating two active molecules of EC33 which inhibit brain APA activity, block the formation of brain AngIII and induce a marked and sustained decrease in BP. The RB150-induced BP decrease is due to a reduced vasopressin release, which increases diuresis, reducing extracellular volume, a decrease in sympathetic tone, leading to a reduction of vascular resistances and the improvement of the baroreflex function (Figure below). RB150 was renamed firibastat by OMS. Phase Ia/Ib clinical trials showed that firibastat is clinically and biologically well-tolerated in healthy volunteers. Firibastat could constitute the first drug candidate of a new class of antihypertensive agents targeting the brain RAS, the clinical efficacy of which (Phase IIa and Phase IIb) in hypertensive patients was achieved. Acknowledgement/Funding INSERM, College de France, ANR LabCom, Quantum Genomics

Chronic metformin reduces systemic and local inflammatory proteins and improves hypertension-related cardiac autonomic dysfunction

Background and aimsMetformin has been known to promote cardiovascular benefits in humans and animal models, even in non-diabetic subjects. However, its chronic effects on hypertension-related autonomic dysfunction remain poorly understood. Therefore, we evaluate the cardiac autonomic effects of chronic metformin in hypertensive rats. Methods and resultsTwelve-week-old male SHR and Wistar rats were separated into 3 groups: WN (Wistar normotensive); SC (SHR hypertensive control); and SM (SHR: Metformin 300 mg/kg/day for 30 days). Spontaneous and induced (by phenylephrine and sodium nitroprusside) baroreflexes were analysed in catheterised rats. Next, cardiac autonomic tone was evaluated through heart rate shift by atropine (parasympathetic) or atenolol (sympathetic). Plasma TNFα was assessed by ELISA. Western blot analyses of inflammatory, oxidant and antioxidant proteins were performed. Cardiac parasympathetic tone and baroreflex function were lower in SC than in WN, whereas cardiac sympathetic tone was higher. Metformin treatment in non-diabetic hypertensive rats reduced the resting heart rate, attenuated the cardiac sympathetic tone and improved baroreflex (especially in the offsetting of rising BP), while blood pressure and glycaemia remained unchanged. Cardiac sympathetic tone correlated negatively with spontaneous baroreflex. Metformin reduced plasma TNFα levels and decreased tissue expression of COX2 and NOX2 (which were positively correlated), without affecting SOD1 and SOD2. ConclusionChronic metformin presented anti-inflammatory and antioxidant effects and, independently of alterations in glycaemia, it improved cardiac autonomic parameters that are impaired in hypertension, being related to end-organ damage and mortality. These findings open up perspectives for future innovative uses of metformin in cardiovascular diseases, especially in hypertension.

Abstract P107: Role for Endothelin B Receptors in the Maintenance of Heart Rate Baroreflex Function

Rats lacking functional endothelin B (ET B ) receptors are hypertensive, salt-sensitive, and have increased sympathetic tone. Hypertension is also associated with blunted arterial baroreflex sensitivity that can lead to increased cardiovascular risk. Although the endothelin system has been implicated to play a role in baroreflex sensitivity, the role of ET B receptors has not been clearly elucidated. We hypothesized that ET B receptors are necessary for appropriate baroreflex sensitivity. We tested this hypothesis using selective pharmacological blockade of the ET B receptor and using rats that lack functional ET B receptors except in adrenergic tissues (ET B -def rats on WKY background). Anesthetized Sprague-Dawley rats given an intravenous infusion of the ET B receptor antagonist, A-192168 (10 mg/kg), had a blunted heart rate response to phenylephrine-induced pressor ramp compared to post-vehicle baseline (-0.08 ± 0.03 vs. -0.22 ± 0.04 bpm/mmHg; p = 0.048, n = 4). Similarly, anesthetized ET B -def rats had a blunted heart rate response to phenylephrine compared to transgenic controls (0.21 ± 0.07 vs. -0.18 ± 0.04 bpm/mmHg; p = 0.001, n = 3-6/group). ET B -def and transgenic control rats were instrumented with telemetry transmitters (HD-S10 Data Sciences), and mean arterial pressure was recorded for 24 hours and analyzed in 10 second bins. ET B -def rats (n = 6) displayed a significantly higher blood pressure lability compared to transgenic controls (n = 5) as shown by a higher standard deviation of mean arterial blood pressure (11.6 ± 0.2 vs 9.7 ± 0.2 mmHg; p &lt; 0.001) and a greater range of mean arterial blood pressure (85.3 ± 4.0 vs. 68.4 ± 3.6 mmHg; p = 0.01). This increased lability of blood pressure in conscious ET B -def rats is consistent with baroreflex dysfunction. These data support the hypothesis that ET B receptors are integral for appropriate heart rate baroreflex function.

Comparison of Baroreflex Sensitivity and Cardiac Autonomic Function Between Adolescent Athlete and Non-athlete Boys - A Cross-Sectional Study.

Introduction: It is well known that regular physical activity improves cardiovascular health, and higher baroreflex sensitivity and heart rate variability are associated with cardiovascular health. Adolescence is the age when an individual’s behavior is easily modified; early intervention at this stage in terms of physical conditioning or training prevents future cardiovascular risk. Hence, we conceived the present study to assess and compare the baroreflex sensitivity and autonomic function between adolescent athletes and non-athletes.Methods: We recruited school going athletes (n = 30) and non-athlete boys (n = 30) in the 10–19 age group after obtaining their assent and consent from their parents. We assessed height, weight, heart rate, blood pressure, baroreflex sensitivity, and cardiac autonomic function. Comparison between groups was made using the unpaired t-test for height, weight, body mass index, heart rate, blood pressure, and baroreflex sensitivity and using Mann-Whitney U test for cardiac autonomic function parameters.Results: There was a trend for higher baroreflex sensitivity in athletes. Heart rate variability (total power and SDNN) was higher in athletes. The parasympathetic tone was higher in terms of higher RMSSD, and higher HF power. Parasympathetic reactivity was higher in athletes in terms of higher 30:15 ratio and EI ratio.Conclusion: Athletic level physical conditioning has a positive influence on baroreflex function and autonomic function that may prove beneficial to the adolescents’ cardiovascular health.

AT2 and MAS (but not AT1) angiotensinergic receptors in the medial amygdaloid nucleus modulate the baroreflex activity in rats.

The medial amygdaloid nucleus (MeA) is a limbic structure that has been demonstrated to be part of the central circuitry regulating baroreflex function. However, the local neurochemical mechanisms involved in baroreflex control by this forebrain structure is poorly understood. Thus, in the present study, we investigated the specific role of AT1, AT2, and MAS angiotensinergic receptors within the MeA in baroreflex responses in unanesthetized rats. For this, the baroreflex function was assessed using both the pharmacological approach via intravenous infusion of vasoactive agents and the sequence analysis technique. Using the pharmacological approach, we observed that bilateral microinjection of the selective AT2 receptor antagonist PD123319 into the MeA increased the tachycardia evoked by blood pressure decrease, but without affecting the reflex bradycardia caused by blood pressure increase. Besides, bilateral microinjection of the selective MAS receptor antagonist A-779 decreased both tachycardic and bradycardic responses of the baroreflex. The sequence analysis technique indicated that PD123319 into the MeA increased baroreflex effectiveness index while A-779 had an opposite effect. Treatment of the MeA with the selective AT1 receptor antagonist losartan did not affect baroreflex function assessed by either the pharmacological approach or sequence analysis technique. Overall, these findings provide evidence that MAS receptor within the MeA plays a facilitatory role in baroreflex function, whereas local AT2 receptor inhibits cardiac baroreflex responses. Results also indicate that AT1 receptor within the MeA is not involved in the control of baroreflex function.

Sympathetic Nerve Traffic and Arterial Baroreflex Function in Apparent Drug-Resistant Hypertension.

True drug-resistant hypertension (RHT) is characterized by a marked neuroadrenergic activation and reflex alterations compared with the nonresistant hypertensive state. It is unknown however, whether this behavior is specific for the RHT state or is also shared by apparent RHT (ARHT). In 38 middle-age patients with RHT, 44 treated essential controlled hypertensives (HT) and 32 ARHT; we evaluated sphygmomanometric, beat-to-beat (Finapres) and 24-hour (Spacelabs) blood pressure, heart rate and muscle sympathetic nerve traffic (microneurography). Measurements included plasma aldosterone, plasma norepinephrine, homeostasis model assessment index, and spontaneous baroreflex-muscle sympathetic nerve traffic sensitivity. All the various above-mentioned blood pressure values were significantly greater in both RHT and ARHT as compared with HT, while 24-hour blood pressure was significantly lower in ARHT as compared with RHT. In ARHT, muscle sympathetic nerve traffic was significantly lower than RHT (74.8±5.2 versus 89.2±4.8 bursts/100 hb, P<0.01) and similar to HT (69.7±4.8 bursts/100 hb, P=NS). RHT showed, at variance from the other 2 groups, greater plasma aldosterone and homeostasis model assessment index values and an impaired baroreflex function. In RHT, but not in ARHT and HT, muscle sympathetic nerve traffic was significantly and inversely related to baroreflex function (r=-0.40, P<0.02) and directly to plasma aldosterone and homeostasis model assessment index values (r=0.34-0.36, P<0.05). Plasma norepinephrine and heart rate values were not significantly different in the 3 groups. These data provide evidence that the marked sympathetic activation and baroreflex dysfunction detected in RHT is not present in ARHT, which displays a sympathetic and baroreflex profile superimposable to that seen in HT. These differences in the neurogenic function may have important clinical and therapeutic implications.

Influence of inspiratory threshold load on cardiovascular responses to controlled breathing at 0.1 Hz.

Slow, deep breathing is being used as a self-management intervention for various health conditions including pain and hypertension. Stimulation of the arterial baroreceptors and increased vagal modulation are among the proposed mechanisms for the therapeutic effects of slow, deep breathing. We investigated whether adding inspiratory threshold load can enhance the cardiovascular responses to controlled breathing at the frequency of 0.1Hz, a common form of slow, deep breathing. Healthy volunteers (N=29) performed controlled breathing at 0.1Hz (6 breaths/minute) without load and with inspiratory threshold loads of 5 cmH2 O and 10 cmH2 O. Respiratory airflow, heart rate, and blood pressure were continuously recorded. The amplitude of the systolic blood pressure variation during respiratory cycles increased with increasing loads. Respiratory sinus arrhythmia was higher during controlled breathing at 0.1Hz with the load of 10 cmH2 O compared to without load. Baroreflex sensitivity was not affected by loads. The effect of loads on respiratory sinus arrhythmia was mediated by increasing the amplitude of systolic blood pressure variation during respiratory cycles. These results suggest that applying small inspiratory threshold loads during controlled breathing at 0.1Hz increases cardiac vagal modulation by this breathing exercise. This effect seems to be mediated by stronger stimulation of the arterial baroreceptors because of larger systolic blood pressure swings along the respiratory cycle. The potential benefit of long-term practice of controlled breathing at 0.1Hz with inspiratory threshold loads on baroreflex function and cardiac vagal control needs to be investigated, particularly in pain and hypertension patients.

Baroreflex circulation regulation during tilt test in young males with a history of vasovagal syncopes

Background. Vasovagal syncopes (VVS) are relatively often recorded in the population of young people. Objective. To establish the changes in the baroreflex function during the tilt test in healthy young males with the history of VVS. Design and methods. A total of 102 people aged 18–30 years were examined and divided into 4 groups, taking into account the specific features of fainting history and response to the tilt test. Subjects of the group 1 (n = 14) had a history of VVS and a positive response to the tilt test (syncope). Subjects of the group 2 (n = 14) had a history of VVS and a pattern of postural tachycardia without fainting verified during the tilt test. Subjects of the group 3 (n = 42) had a history of VVS and a negative response to the tilt test. Subjects of the group 4 (n = 32) did not have a history of VVS and showed a negative response to the tilt test. During the tilt test, we studied the dynamics of the baroreflex functional parameters (the number of baroreflex reactions (NBR), the baroreflex effectiveness index (BEI), the baroreflex sensitivity (BRS)). Results. In the individuals of each group, in the initial horizontal phase, values of NBR, BEI, BRS were within normal range and did not show significant intergroup differences (p &gt; 0,05). The passive orthostasis was associated with the increase in NBR (in each group beside control group), a decrease in BEI and BRS. The increase in NBR in the vertical phase of the tilt test (relative to the initial horizontal phase) was 87 %, 6 %, 16 % in the groups 1, 2, 3 and 4, respectively. The tilt-induced decrease in NBR comprised 8 % in the group 4. The decrease in the BEI in the vertical phase of the tilt test (relative to the initial horizontal phase) consisted: 22 %, 19 %, 12 %, 10 % in subjects of the 1, 2, 3, 4 groups, respectively. During the passive orthostasis we observed a decrease in BRS: by 65 %, 69 %, 64 %, 57 % in individuals of the groups 1, 2, 3 and 4, respectively. Returning from a vertical to a horizontal position in all groups led to a pronounced decrease in NBR and an increase in the BEI to values lower than in baseline horizontal tilt test phase; to an excessive increase in the BRS exceeding the pre-test values in each study group. Conclusions. In prolonged passive orthostasis, healthy young males, regardless of the fainting history, demonstrate a decrease in the baroreflex regulation. Among those with the history of VVS, tilt-positive subjects are characterized by a more pronounced orthostasis-induced drop in the baroreflex sensitivity and the baroreflex effectiveness index and a slow recovery of the baroreflex regulatory function compared to the tilt-negative subjects and to those who demonstrated postural tachycardia pattern without syncope.

Closed-loop modeling of the heart-rate reflex for improved diagnosis and monitoring of Mild Cognitive Impairment.

Analysis of beat-to-beat spontaneous cerebral hemodynamic data has yielded predictive dynamic models of cerebral hemodynamics and has shown previously that patients with Mild Cognitive Impairment (MCI) exhibit significantly reduced cerebral vasomotor reactivity to CO2 relative to cognitively normal control subjects [1]. The present work examines the heart-rate reflex (HRR) dynamics of 46 MCI patients compared to 20 control subjects, using closed-loop modeling of HRR under resting conditions of spontaneous variations of arterial blood pressure (baroreflex) and end-tidal CO2 (chemoreflex). These subject-specific predictive dynamic models are obtained via the methodology of Principal Dynamic Modes [2] and allow the computation of model-based markers of baroreflex and chemoreflex function. We found that the chemoreflex gain is significantly weakened in MCI patients relative to controls (p=0.0086), while the baroreflex is not significantly affected. These findings offer another tool for diagnosis and monitoring of MCI (via model-based markers), when used in conjunction with current methods.

Time Course of Hemodynamic Responses to Different Doses of Lipopolysaccharide in Unanesthetized Male Rats.

Lipopolysaccharide (LPS) administration is a well-known method to induce systemic inflammation widely used for investigating new therapeutic strategies for sepsis treatment, which is characterized by clinical manifestations such as tachycardia and hypotension. However, there are different doses of LPS used in several studies, and the hemodynamic responses were not always well characterized. Thus, the present study aimed to evaluate the arterial pressure, heart rate, heart rate variability, and baroreflex function from rats, over time, to different doses of LPS. Femoral artery and vein catheters were inserted into anesthetized Wistar-Hannover male rats for arterial pressure recording and LPS administration, respectively. On the next day, the arterial pressure was recorded before and after (90, 180, and 360 min) LPS injection (0.06, 20, 30, and 40 mg/kg). All doses of LPS tested increased the heart rate and decreased baroreflex sensitivity over time. In addition, while LPS administration of 20, 30, and 40 mg/kg increased the mean arterial pressure over time, 0.06 mg/kg decreased the mean arterial pressure at 360 min, as compared to baseline values. Furthermore, high doses of LPS decreased the power of the HF band of the cardiac interval spectrum over time, and the higher dose increased the power of the LF band. Our data indicate that high doses of LPS promote hypertensive response over time, while a low dose decreases arterial pressure. Moreover, the changes in heart rate variability and baroreflex function elicited by LPS may be not associated with arterial pressure response produced by the endotoxemia.

Suppressed baroreflex peripheral arc overwhelms augmented neural arc and incapacitates baroreflex function in rats with pulmonary arterial hypertension.

What is the central question of this study? The impact of pulmonary arterial hypertension on open-loop baroreflex function, which determines how powerfully and rapidly the baroreflex operates to regulate arterial pressure, remains poorly understood. What is the main finding and its importance? The gain of the baroreflex total arc, indicating the baroreflex pressure-stabilizing function, is markedly attenuated in rats with monocrotaline-induced pulmonary arterial hypertension. This is caused by a rightward shift of the baroreflex neural arc and a downward shift of the peripheral arc. These findings contribute greatly to our understanding of arterial pressure regulation by the sympathetic nervous system in pulmonary arterial hypertension. Sympathoexcitation has been documented in patients with established pulmonary arterial hypertension (PAH). Although the arterial baroreflex is the main negative feedback regulator of sympathetic nerve activity (SNA), the way in which PAH impacts baroreflex function remains poorly understood. In this study, we conducted baroreflex open-loop analysis in a rat model of PAH. Sprague-Dawley rats were injected with monocrotaline (MCT) s.c. to induce PAH (60mgkg-1 ; n=11) or saline as a control group (CTL; n=8). At 3.5weeks after MCT injection, bilateral carotid sinuses were isolated, and intrasinus pressure (CSP) was controlled while SNA at the coeliac ganglia and arterial pressure (AP) were recorded. To examine the static baroreflex function, CSP was increased stepwise while steady-state AP (total arc) and SNA (neural arc) responses to CSP and the AP response to SNA (peripheral arc) were measured. Monocrotaline significantly decreased the static gain of the baroreflex total arc at the operating AP compared with CTL (-0.80±0.31 versus -0.22±0.22, P<0.05). Given that MCT markedly increased plasma noradrenaline, an index of SNA, by approximately 3.6-fold compared with CTL, calibrating SNA by plasma noradrenaline revealed that MCT shifted the neural arc to a higher SNA level and shifted the peripheral arc downwards. Monocrotaline also decreased the dynamic gain of the baroreflex total arc (-0.79±0.16 versus -0.35±0.17, P<0.05), while the corner frequencies that reflect the speed of the baroreflex remained unchanged (0.06±0.02 versus 0.08±0.02Hz, n.s.). In rats with MCT-induced PAH, the suppressed baroreflex peripheral arc overwhelms the augmented neural arc and, in turn, attenuates the gain of the total arc, which determines the pressure-stabilizing capacity of the baroreflex.