Impaired Baroreflex Sensitivity Research Articles

Patient-Specific Factors Predicting Renal Denervation Response in Patients With Hypertension: A Systematic Review and Meta-Analysis.

The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient-specific factors predicting the RDN response. We focused on individuals with hypertension who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the overall quality of evidence. A total of 50 studies were ultimately included in this systematic review, among which 17 studies were for meta-analysis. Higher baseline heart rate and lower pulse wave velocity were shown to be associated with significant antihypertensive efficacy of RDN on 24-hour systolic BP reduction (weighted mean difference, -4.05 [95% CI, -7.33 to -0.77]; weighted mean difference, -7.20 [95% CI, -9.79 to -4.62], respectively). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension, impaired baroreflex sensitivity, and several biomarkers are also reported to be associated with significant BP reduction after RDN. In patients with hypertension treated with the RDN, higher heart rate, and lower pulse wave velocity were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with orthostatic hypertension, BP variability, impaired cardiac baroreflex sensitivity, and some biomarkers are also reported to be associated with a better BP response to RDN.

Young Trauma-Exposed Women with Low Sleep Effciency have Blunted Sympathetic Baroreflex Sensitivity and Higher Muscle Sympathetic Nerve Activity

Introduction: Poor sleep, a known risk factor for cardiovascular disease (CVD) and one of the American Heart Association’s essential 8th, is common after trauma-exposure. Although premenopausal women are thought to be protected from CVD, trauma exposure might increase their CVD risk. In a recent large epidemiological study examining sleep-related CVD comorbidities, the empirical cut off point for optimal sleep effciency (SE) was set at 83%, distinguishing between good and poor sleep effciency. Studies have suggested an overactive sympathetic nervous system and an impaired baroreflex sensitivity (BRS) as potential mechanisms of increased CVD risk. However, the impact of poor sleep effciency on muscle sympathetic nerve activity (MSNA) and BRS in young trauma-exposed women is unknown. We hypothesized that young trauma-exposed women with poor sleep effciency will present with impaired BRS and increased MSNA at rest. Methods: We collected data on 30 women (18 – 40 years) from diverse backgrounds who had been exposed to trauma. Sleep data was acquired via ActiWatch for 7 days and used to categorize our participants into two groups: good effciency (SE > 83%, n=17) and poor effciency (SE < 83%, n=13), with SE calculated as the percentage of time spent asleep while in bed. Additionally, we collected continuous noninvasive blood pressure (BP), heart rate (HR), and MSNA (burst frequency, incidence, and total activity) during 10 minutes of quiet rest. Sympathetic BRS was determined as the slope of the regression between individual sympathetic bursts and diastolic BP bins (3 mmHg), weighted against the number of cardiac cycles, utilizing an automated program (Ensemble, NZ). Results: There were no significant differences in trauma symptom severity, resting BP and HR between the two groups (p>0.05 for all). However, resting sympathetic BRS was blunted in the poor SE (-0.10±0.88 bursts/100hb/mmHg) compared to the good SE (-1.44±1.58 bursts/100hb/mmHg, p=0.006) group, even after adjusting for age (p=0.009). Likewise, resting total MSNA was higher in the poor SE compared to the good SE after adjusting for age (p=0.028). MSNA burst frequency and burst incidence were comparable between the groups (p>0.05). Conclusion: Our analyses revealed that poor sleep effciency is associated with decreased sympathetic baroreflex sensitivity and higher total muscle sympathetic activity at rest, regardless of age. Blunted sympathetic BRS may contribute to increased sympathetic activity in young women with poor sleep effciency. Future studies testing strategies to improve sleep effciency in this population could provide potential long-term cardiovascular benefits. UL1TR002494 and NIH K01HL161027 No disclosure. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sleep deprivation reduces the baroreflex sensitivity through elevated angiotensin (Ang) II subtype 1 receptor expression in the nucleus tractus solitarii.

Sleep insufficiency has been linked to an increased risk of high blood pressure and cardiovascular diseases. Emerging studies have demonstrated that impaired baroreflex sensitivity (BRS) is involved in the adverse cardiovascular effects caused by sleep deprivation, however, the underlying mechanisms remain unknown. Therefore, the present study aims to clarify the role of abnormal renin-angiotensin system in the nucleus tractus solitarii (NTS) in impaired BRS induced by sleep deprivation. Rats were randomly divided into two groups: normal sleep (Ctrl) and chronic sleep deprivation (CSD) group. Rats were sleep deprived by an automated sleep deprivation system. The blood pressure, heart rate, BRS, the number of c-Fos positive cells and the expression of angiotensin (Ang) II subtype 1 receptors (AT1R) in the NTS of rats were assessed. Compared to Ctrl group, CSD group exhibited a higher blood pressure, heart rate, and reduced BRS. Moreover, the number of c-Fos positive cells and local field potential in the NTS in CSD group were increased compared with the Ctrl group. It was shown that the expression of the AT1R and the content of Ang II and the ratio of Ang II to Ang-(1-7) were increased in the NTS of rats in CSD group compared to Ctrl group. In addition, microinjection of losartan into the NTS significantly improved the impaired BRS caused by sleep deprivation. In conclusion, these data suggest that the elevated AT1R expression in the NTS mediates the reduced BRS induced by chronic sleep deprivation.

Assessment of Heart Rate Variability in Children with Mitral Valve Prolapse.

Mitral valve prolapse (MVP) is a heart valve anomaly with specific electrocardiographic findings and arrhythmia. A predominant sympathetic tone and diminished vagal activity have been reported especially in symptomatic MVP patients. In the current study, we aim to review heart rate variability (HRV) parameters of MVP children in order to determine if there is an impaired autonomic regulation. The data of children with MVP were retrospectively analyzed. Demographic characteristics, body mass index, symptomatology, MVP type and mitral regurgitation, MVP-related electrocardiographic changes, arrhythmia, and HRV parameters in 24-h Holter monitoring were recorded. HRV parameters of the control group were obtained from children applying for sport participation. Statistical significance limit was accepted as p < 0.05. 154 of the patients (74.8%) were girls, the median age was 13.58 ± 2.99years. While MVP patients had shorter PR intervals, those who had syncope had longer PR intervals. Short PR distance may be a feature of MVP, long PR distance may be a condition associated with syncope with the underlying paroxysmal atrioventricular block. Moreover, the minimum heart rate was significantly lower in the MVP group compared to the control and there were no significant differences in terms of remaining parameters. The number of low LF values was higher in MVP patients than the control. Comparing HRV values of groups by gender, we found that overall HRV parameters were lower in girls with MVP while minimum, maximum, and average heart rate were lower in boys with MVP. Impaired HRV associated with MVP could be age, gender, and symptom related. In addition, low LF may indicate impaired baroreflex sensitivity in MVP patients.

Sodium overload during postnatal phases impairs diastolic function and exacerbates reperfusion arrhythmias in adult rats

Abstract Sodium overload during childhood impairs baroreflex sensitivity and increases arterial blood pressure and heart rate in adulthood; these effects persist even after high-salt diet (HSD) withdrawal. However, the literature lacks details on the effects of HSD during postnatal phases on cardiac ischemia/reperfusion responses in adulthood. The current study aimed to elucidate the impact of HSD during infancy adolescence on isolated heart function and cardiac ischemia/reperfusion responses in adulthood. Male 21-day-old Wistar rats were treated for 60 days with hypertonic saline solution (NaCl; 0.3M; experimental group) or tap water (control group). Subsequently, both groups were maintained on a normal sodium diet for 30 days. Subsequently, the rats were euthanized, and their hearts were isolated and perfused according to the Langendorff technique. After 30 min of the basal period, the hearts were subjected to 20 min of anoxia, followed by 20 min of reperfusion. The basal contractile function was unaffected by HSD. However, HSD elevated the left ventricular end-diastolic pressure during reperfusion (23.1 ± 5.2 mmHg vs. 11.6 ± 1.4 mmHg; p &lt; 0.05) and increased ectopic incidence period during reperfusion (208.8 ± 32.9s vs. 75.0 ± 7.8s; p &lt; 0.05). In conclusion, sodium overload compromises cardiac function after reperfusion events, diminishes ventricular relaxation, and increases the severity of arrhythmias, suggesting a possible arrhythmogenic effect of HSD in the postnatal phases.

Parental fructose consumption induces early baroreflex dysfunction in offspring: impact on arterial pressure and on insulin resistance.

Fructose overconsumption is a worldwide trend, and it has been found to cause metabolic disorders in parents and their offspring. Additionally, metabolic syndrome has been closely associated with increased cardiovascular risk. In this study, we hypothesized that the chronic fructose consumption by parents could trigger autonomic dysfunction and cardiometabolic disorders in their offspring. Wistar rats undergo an intake of 10% of fructose in drinking water or regular water for 60 days before mating. Their offspring, control (C) and fructose (F) groups, were evaluated 30 days after weaning. Lower birth weight, increased levels of blood triglycerides and insulin resistance were observed in F compared to C group. The offspring of the fructose parents showed increased mean arterial pressure (C: 104 ± 1 vs. F: 111 ± 2 mmHg) and baroreflex sensitivity impairment, characterized by reduced bradycardic (C: -1.6 ± 0.06 vs. F: -1.3 ± 0.06 bpm/mmHg) and tachycardic responses (C: -4.0 ± 0.1 vs. F: -3.1 ± 0.2 bpm/mmHg). Finally, a higher baroreflex-induced tachycardia was associated with lower insulin tolerance (r = -0.55, P < 0.03) and higher systolic arterial pressure (r = 0.54, P < 0.02). In conclusion, our findings indicate that the excessive consumption of fructose by parents is associated with early autonomic, cardiovascular, and metabolic derangement in the offspring, favoring an increased cardiometabolic risk when they reach adulthood.

Baroreflex sensitivity is impaired in survivors of mild COVID-19 at 3-6 months of clinical recovery; association with carotid artery stiffness.

The association between the stiffening of barosensitive regions of central arteries and the derangements in baroreflex functions remains unexplored in COVID-19 survivors. Fifty-seven survivors of mild COVID-19 (defined as presence of upper respiratory tract symptoms and/or fever without shortness of breath or hypoxia; SpO2 > 93%), with an age range of 22-66 years (27 females) participated at 3-6 months of recovering from the acute phase of RT-PCR positive COVID-19. Healthy volunteers whose baroreflex sensitivity (BRS) and arterial stiffness data were acquired prior to the onset of the pandemic constituted the control group. BRS was found to be significantly lower in the COVID survivor group for the systolic blood pressure-based sequences (BRSSBP ) [9.78 (7.16-17.74) ms/mmHg vs 16.5 (11.25-23.78) ms/mmHg; p = 0.0253]. The COVID survivor group showed significantly higher carotid β stiffness index [7.16 (5.75-8.18) vs 5.64 (4.34-6.96); (p = 0.0004)], and pulse wave velocity β (PWVβ ) [5.67 (4.96-6.32) m/s vs 5.12 (4.37-5.41) m/s; p = 0.0002]. BRS quantified by both the sequence and spectral methods showed an inverse correlation with PWVβ in the male survivors. Impairment of BRS in the male survivors of mild COVID-19 at 3-6 months of clinical recovery shows association with carotid artery stiffness.

Sex differences in Black Veterans with PTSD: women versus men have higher sympathetic activity, inflammation, and blunted cardiovagal baroreflex sensitivity.

Post-traumatic stress disorder (PTSD) is associated with greater risk of incident hypertension and cardiovascular disease (CVD). Inflammation and autonomic derangements are suggested as contributing mechanisms. Women and Black adults have higher CVD risk associated with stress; however, whether there is a sex difference in autonomic and inflammatory mechanisms among Black individuals with PTSD is not known. We hypothesized that Black women with PTSD have higher inflammation, sympathetic nervous system (SNS) activity and impaired baroreflex sensitivity (BRS). In 42 Black Veterans with PTSD (Women, N = 18 and Men, N = 24), we measured inflammatory biomarkers, continuous blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) at rest and during arterial BRS testing via the modified Oxford technique. Groups were matched for age and body mass index (BMI). Resting BP was similar between groups, but HR was higher (76 ± 12 vs. 68 ± 9 beats/min, p = 0.021) in women compared to men. Although women had lower PTSD symptoms severity (57 ± 17 vs. 68 ± 12 a.u.), resting MSNA (27 ± 13 vs. 16 ± 5 bursts/min, p = 0.003) was higher in women compared to men, respectively. Likewise, cardiovagal BRS was blunted (p = 0.002) in women (7.6 ± 4.3ms/mmHg) compared to men (15.5 ± 8.4ms/mmHg) while sympathetic BRS was not different between groups (p = 0.381). Black women also had higher (p = 0.020) plasma levels of interleukin-2 (IL-2). Black women with PTSD have higher resting HR and MSNA, greater impairment of cardiovagal BRS and possibly higher inflammation. These findings suggest a higher burden of autonomic and inflammatory derangements in Black women compared to Black men with PTSD.

Maternal Hyperglycemia Induces Autonomic Dysfunction and Heart Failure in Older Adult Offspring.

Offspring exposed to an adverse fetal environment, such as gestational diabetes, may manifest increased susceptibility to several chronic diseases later in life. In the present study, the cardiovascular function of three different ages of offspring from diabetic rats was evaluated. Diabetes mellitus was induced in pregnant rats by a single dose of streptozotocin (50 mg/kg). The offspring from diabetic (OD) and control rats (OC) were evaluated at three different ages: 6, 12 or 18 months. In the corresponding OC groups, fasting glycemia, baseline mean arterial pressure, and sympathetic tonus increased in the OD rats at 12 (OD12) and 18 (OD18) months of age, while cardiac hypertrophy was observed in all OD groups. Cardiac function evaluation in vivo showed low left ventricular systolic pressure and+dP/dt in the OD18 rats, suggesting a systolic dysfunction. OD12 and OD18 groups showed high left ventricle end-diastolic pressure, suggesting a diastolic dysfunction. OD groups showed an age-related impairment of both baroreflex-mediated tachycardia and baroreflex-mediated bradycardia in OD12 and OD18 rats. In isolated hearts from OD18 rats, both inotropic and tachycardiac responses to increasing isoproterenol were significantly reduced compared to the corresponding OC group. These results suggest that gestational diabetes triggers the onset of hyperglycemia hypertension with impaired baroreflex sensitivity and heart failure in older age of offspring, representing important risk factors for death. Therefore, ensuring optimal glycemic control in diabetic pregnancy is important and serves as a key to preventing cardiovascular disease in the offspring in their older age.

Autonomic modulation, spontaneous baroreflex sensitivity and fatigue in young men after COVID-19.

Impaired autonomic modulation and baroreflex sensitivity (BRS) have been reported during and after COVID-19. Both impairments are associated with negative cardiovascular outcomes. If these impairments were to exist undetected in young men after COVID-19, they could lead to negative cardiovascular outcomes. Fatigue is associated with autonomic dysfunction during and after COVID-19. It is unclear if fatigue can be used as an indicator of impaired autonomic modulation and BRS after COVID-19. This study aims to compare parasympathetic modulation, sympathetic modulation, and BRS between young men who had COVID-19 versus controls and to determine if fatigue is associated with impaired autonomic modulation and BRS. Parasympathetic modulation as the high-frequency power of R-R intervals (lnHFR-R), sympathetic modulation as the low-frequency power of systolic blood pressure variability (LFSBP), and BRS as the -index were measured by power spectral density analysis. These variables were compared between 20 young men who had COVID-19 and 24 controls. Independent t-tests and Mann-Whitney U tests indicated no significant difference between the COVID-19 and the control group in: lnHFR-R, P=0.20; LFSBP, P=0.11, and -index, P=0.20. Fatigue was not associated with impaired autonomic modulation or BRS. There is no difference in autonomic modulations or BRS between young men who had COVID-19 compared to controls. Fatigue did not seem to be associated with impaired autonomic modulation or impaired BRS in young men after COVID-19. Findings suggest that young men might not be at increased cardiovascular risk from COVID-19-related dysautonomia and impaired BRS.

Testosterone effects on autonomic function in women with androgen excess polycystic ovary syndrome

Women with androgen excess-polycystic ovarian syndrome (AE-PCOS) present with increased blood pressure (BP) and impaired cardiovascular autonomic control. We tested the hypothesis that androgens play an obesity-independent role in impaired baroreflex (BR) sensitivity and renin-angiotensin system (RAS) control of BP in women with AE-PCOS. We measured the sympathetic baroreflex (sBR) and cardiovagal baroreflex (cvBR) with the modified Oxford procedure, and integrated baroreflex (iBR) and the RAS response to lower body negative pressure (LBNP) in obese, insulin resistant (IR) women with AE-PCOS (n=9; age=23±4 y; BMI=36.3±6.4 kg/m2) and obese, IR controls (CTL) (n=7; age=29±7 y; BMI=34.9±6.8 kg/m2). Studies were conducted at baseline (BSL), after 4 days of reproductive hormone suppression with a gonadotropin-releasing hormone antagonist (ANT, 250 μg/day), and after 4 days of ANT+testosterone (ANT+T, 5 mg/day). At BSL, AE-PCOS and CTL had similar systolic BP (137±14 vs.133±14 mmHg, respectively) and diastolic BP (76±8 vs.63±12 mmHg, respectively). Resting MSNA burst incidence was lower (10.3±3.1 vs. 14.3±4.4 bursts-1×100 hb, P=0.04), but total MSNA activity was greater in AE-PCOS compared to CTL (249±112 vs. 156±44 bursts/min, respectively, P=0.04). Hormone intervention did not impact resting MSNA or BP in either group. In the AE-PCOS group, sBR gain increased during modified Oxford with ANT suppression of T, but sBR gain was restored to BSL when T was reintroduced (-0.48±0.15, -0.63±0.19, and -0.50±0.15 bursts -1 ·100 hb·mmHg -1 for BSL, ANT and ANT+T, respectively, P=0.01). Hormone interventions did not impact sBR gain in CTL (-0.48±0.06, -0.47±0.10, and -0.46±0.09 bursts -1 ·100 hb·mmHg -1 for BSL, ANT and ANT+T, respectively). iBR gain for AE-PCOS and CTL was similar at BSL (1.4±0.9 vs. 1.0±1.3 FVR unit/mmHg, respectively). In AE-PCOS, T suppression increased iBR gain, which was restored to BSL with ANT+T (4.3±6.5 vs.1.5±0.8 FVR unit/mmHg for ANT and ANT+T respectively, P&lt;0.04), with no effect in CTL (1.9 ± 3.0 vs. 0.7±0.9 FVR unit/mmHg for ANT and ANT+T, respectively). cvBR gain was unaffected by group or treatment. Serum aldosterone was greater in AE-PCOS vs CTL (136.5±60.2 vs. 75.7±41.4 pg/ml, respectively, P&lt;0.04), but unaffected by hormone intervention. Serum angiotensin converting enzyme (S [ACE] ) in AE-PCOS was greater compared to CTL at BSL (101.9±93.4 vs. 38.2 ±14.7 pg/ml, respectively, P&lt;0.04). In AE-PCOS, S [ACE] was reduced by ANT (77.7 ±76.5 and 40.6±10.6 μg/L for ANT vs. ANT+T, respectively, P&lt;0.04), but hormone intervention did not impact CTL (43.4±27.3 and 40.6±1 μg/L for ANT vs. ANT+T, respectively, P&lt;0.04). These data suggest the milieu of AE-PCOS increases susceptibility to T driven autonomic perturbations as T elevation had differential effects in AE-PCOS vs. CTL. Our data indicate a powerful relationship among elevated androgens, autonomic function, and the kidney.NIH HL135089/P20GM 121334 National Institutes of Health, NHLBI HL135089 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

Effect of acute hyperglycemia on baroreflex sensitivity in healthy young adults.

Autonomic dysfunction, impaired baroreflex sensitivity (BRS), and deranged circulatory homeostasis have been observed in chronic hyperglycemia and found to be associated with increased cardiovascular morbidity and mortality. However, the acute effects of hyperglycemia in healthy subjects have been rarely studied. The present study explores the effect of acute hyperglycemia on conventional and unconventional parameters of BRS in healthy young adults. For the estimation of BRS beat-to-beat blood pressure (BP) and electrocardiogram were recorded in forty-two young, healthy subjects during fasting and at 1hr of the oral glucose load. Analysis of BRS was carried out by sequence and spectral method. Number of UP-, DOWN- and ALL-sequences between ramps of BP and RR-interval were calculated as an unconventional measure of BRS along with the other conventional parameters. We observed significant alteration of unconventional parameters of autonomic functions [the number of sequences of UP- (p = 0.0039) and ALL-sequences (p = 0.0233) of systolic BP and RR interval; and, UP- (p = 0.0380), DOWN- (p = 0.0417) and ALL-sequences (p = 0.0313) of mean BP and RR- interval] during acute hyperglycemia as compared to the fasting state. However, no significant changes were observed in any of the conventional parameters of BRS during acute hyperglycemia as compared to the fasting state. Present study concludes that the unconventional parameters of BRS - the number of sequences between the ramp of BP and RR-interval - change significantly during acute hyperglycemia. However, the conventional parameters do not show significant changes during acute hyperglycemia. We may hypothesize that the relatively constant BRS is maintained at the expense of increased oscillations in the ramp of BP and RR-interval.

Pregnancy restores altered sympathetic vasomotor modulation and parasympathetic cardiac modulation in hypertensive rats

Hypertension is associated to impaired baroreflex sensitivity (BRS). In spontaneously hypertensive rats (SHR), pregnancy reduces blood pressure, and this effect has been associated to increase nitric oxide (NO) bioavailability. Increased NO bioavailability has been linked to improve BRS in hypertensive animals. Therefore, we hypothesize that pregnancy improves the BRS in SHR. We performed experiments to evaluate the vasomotor and cardiac autonomic modulation, also to evaluate the BRS at baseline conditions (spontaneous) and after phenylephrine (PE) and sodium nitroprusside (SNP) administrations in non-pregnant (NP) and pregnant (P) Wistar rats and SHR. Beat-to-beat time series with systolic arterial pressure values were generated and processed by Fast Fourier Transform (spectral analysis). Next, spectra were integrated into low-frequency (LF) band and had their power taken as an index of sympathetic modulation on arterial pressure. Reduced mean arterial pressure was observed in P-groups when compared to NP matched rats, although we did not observe alterations in heart rate (HR). In SHR-NP, spectral analysis revealed altered cardiovascular autonomic modulation when compared to the other groups. However, in SHR-P the autonomic parameters were similar to those observed in Wistar-NP, suggesting that pregnancy changed autonomic modulation. BRS assessed by means of the sequence method was found similar in P-groups. Pregnancy reduced the BRS during hypotension in Wistar. BRS assessed with PE and SNP administration was found lower in SHR-NP as compared to Wistar-NP, and it was not altered by pregnancy. In conclusion, pregnancy did not improve the BRS in SHR, but normalized altered sympathetic vasomotor modulation in SHR.

061 Sleep Hygiene as an Intervention to Lower Blood Pressure

Abstract Introduction Insufficient sleep has been shown to increase the risk of a person developing hypertension. Impaired baroreflex sensitivity (BRS) is one of the known underlying mechanisms involved that is responsible for increasing blood pressure (BP). This project investigates the relationship between sleep, BRS, and BP during Valsalva’s Maneuver (VM). Methods Fifty participants (59.8 ± 1.5 years; 31 women) completed 3 overnight in-hospital stays. The first stay (S1) was a baseline control; the second stay (S2) followed a 4-week wait-list control condition; the third stay (S3) followed an 8-week randomly assigned intervention that used sleep hygiene approaches and scheduling to either A) stabilize sleep timing, or B) stabilize and extend the bed period. The study is still ongoing, and we are blind to whether participants were randomized to arm A or B of the study. A linear regression model analyzing the R-R Interval (RRI) and corresponding systolic BP was used to calculate the BRS function and the maximum change in SBP (BPMax) during Early Phase II (EPII) of VM. Results There was an increasing BRS trend across the three stays during EPII (p=.051). There was no significant increase between S1 and S2 (p=.876), but BRS significantly increased following 8 weeks of intervention at S3 compared to S1 (p=0.033) and S2 (p=0.037). There was also a significant decrease in BPMax across the three stays during EPII (p&amp;lt;.001). There was no significant decrease in EPII BPMax between S1 and S2 (p=.325), but BPMax significantly decreased in S3 compared to S1 (p&amp;lt;0.001) and S2 (p=0.002). Conclusion While we are still blind to condition, both conditions are considered active as they both involve stabilizing the sleep period using sleep hygiene. These preliminary data suggest that stabilization of sleep timing and possibly duration, has a positive impact on BP regulation. Support (if any) NIH (R01HL125379 to Dr. Janet Mullington), Harvard Catalyst, Harvard Clinical and Translational Science Center (UL1TR001102).

Hypoglycemia Impairs Baroreflex Sensitivity: Implications for Autonomic Control of Cardiovascular Function in Diabetes

Background: Iatrogenic hypoglycemia is an unintended, though common, occurrence in individuals with diabetes. There is a clear association between hypoglycemia exposure and an increase in mortality in individuals with type 2 diabetes (T2DM). It is well-established that recurrent hypoglycemic episodes impair the counterregulatory hormone responses; however, it is yet to be determined if in T2DM there are more global effects of hypoglycemia on autonomic control of cardiovascular function (baroreflex sensitivity, BRS), as has been shown in healthy individuals. This is a clinically relevant knowledge gap as decreases in BRS are pro-arrhythmogenic and associated with decreases in mortality in individuals with diabetes. Objective: We tested the hypothesis that in individuals with T2DM, hypoglycemia impairs baroreflex sensitivity (BRS), a robust measure of cardiovascular autonomic control. Methods: Individuals with well-controlled T2DM and without known cardiovascular disease were exposed to two 90-minute episodes of experimental hypoglycemia (50 mg/dl) in the same day. All individuals experienced a hypoglycemic-hyperinsulinemic clamp in the morning (AM clamp) and again in the afternoon (PM clamp). BRS was assessed using the modified Oxford method (sequential administration of nitroprusside and phenylephrine) before the initiation of each hypoglycemic-hyperinsulinemic clamp, during the last 30 minutes of hypoglycemia, and the following day. Results: The study included 16 individuals with a diagnosis of T2DM (6 men and 10 women) with the following characteristics (mean ± SD): age 45 ± 11 years, BMI 32 ± 6 kg/m2, hemoglobin A1c 6.4 ± 0.9%, and diabetes duration 8 ± 5 years. At baseline, individuals with T2DM had a BRS of 7.7 ± 3.6 ms/mmHg, which is reduced compared to a BRS of 21.3 ± 13.8 ms/mmHg in a historical healthy control group of 54 subjects (p<0.001). A mixed effects model adjusting for sex, age, BMI, and insulin level, demonstrated a significant effect of hypoglycemia on BRS (p=0.008). Pairwise comparisons revealed a significant decrease in BRS during the PM clamp as compared with BRS assessed at baseline (5.5 ± 5.0 vs 7.7 ± 3.6 ms/mmHg, p=0.045), during the AM clamp (5.5 ± 5.0 vs 10.5 ± 5.6 ms/mmHg, p=0.43), and the following day (5.5 ± 5.0 vs 8.6 ± 3.8 ms/mmHg, p=0.33). Of note, there was no significant difference between BRS at baseline and during the AM clamp (p=0.44). Additionally, insulin levels positively and strongly correlated with BRS at baseline (R2 0.52) and during the AM clamp (R2 0.67). Discussion: Insulin may have a stimulatory effect on BRS during a hyperinsulinemic hypoglycemic clamp that counters the inhibitory effect of hypoglycemia during the first episode of hypoglycemia. However, with exposure to a second hypoglycemic clamp, BRS decreases. Conclusion: Individuals with T2DM have low BRS at baseline, which is further reduced after 2 episodes of hypoglycemia.

Sublingual Nitroglycerin Acutely Alters Cardiovagal and Sympathetic Baroreflex Sensitivity in Healthy Humans

Augmented sympathetic nerve activity (SNA) and impaired baroreflex sensitivity (BRS) are important therapeutic targets in patients with cardiovascular diseases. Nitroglycerin (glyceryl trinitrate, GTN) is a vasodilator, widely used in patients with coronary artery diseases, however, the effects of GTN on SNA and BRS are incompletely understood. Importantly, the acute effects of GTN on SNA and BRS are not clear. Additionally, there are no reports evaluating both the sympathetic BRS (SBRS) and cardiovagal BRS (CBRS) responses to the administration of sublingual GTN. The purpose of this study was to assess the acute effects of GTN on muscle sympathetic nerve activity (MSNA), SBRS and CBRS in healthy subjects. We hypothesized that sublingual GTN would rapidly modulate sympathetic and cardiovagal BRS and thus increase MSNA in healthy subjects. Ten (9M, 1F) healthy subjects (60 ± 2 yrs) without medications were examined. Beat-to-beat heart rate (HR), arterial pressure (AP) and MSNA were recorded before and for 10 min after sublingual administration of GTN 0.4 mg. SBRS was evaluated by analyzing the relationship between spontaneous variations in diastolic AP and MSNA. CBRS was assessed with the sequence technique. Every 2 min HR, AP and MSNA data were recorded and compared. SBRS and CBRS were assessed during baseline, and during min 3-6 (Post A) and 7-10 min (Post B) after GTN administration. Compared to baseline, mean AP did not significantly change during Post A (baseline, 98.5 ± 1.8 to 95.6 ± 2.3 mmHg, P = 0.423) but decreased during Post B (91.9 ± 2.2 mmHg, P < 0.05). MSNA increased significantly by min 2 after GTN and remained significantly elevated during both the Post A and Post B periods (31.2 ± 4.0 to 48.2 ± 4.4, and 47.5 ± 4.2; bursts/min, both P < 0.05). Compared to baseline, during the Post A and Post B periods CBRS decreased significantly (12.9 ± 1.6 to 7.1 ± 1.0, and 6.4 ± 0.6; ms･mmHg-1, both P < 0.05), while SBRS increased significantly (0.8 ± 0.2 to 1.5 ± 0.2, and 1.8 ± 0.3; units･beat-1･mmHg-1, both P < 0.05). The SBRS operating point was also reset and shifted to upward during both the Post A and Post B periods. The results show that a clinical sublingual dose of GTN attenuated the CBRS and raised the SBRS with an upward shift of the operating point, resulting in augmented MSNA. Whether these acute changes in MSNA and BRS with GTN in the absence of changes in BP can evoke adverse sequelae in patients with atherosclerosis is unknown. These findings have never been reported before. These factors should be considered by clinicians as they use this agent.

Yoga Practitioners Exhibit Higher Parasympathetic Activity and Baroreflex Sensitivity and Better Adaptability to 40 mm Hg Lower-Body Negative Pressure.

Yoga has been shown to improve autonomic conditioning in humans, as evidenced by the enhancement of parasym-pathetic activity and baroreflex sensitivity. Therefore, we hypothesized that the experience of yoga may result in adaptation to acute hemodynamic changes. To decipher the long-term effects of yoga on cardiovascular variability, yoga practitioners were compared to yoga-naïve subjects during exposure to -40 mm Hg lower-body negative pressure (LBNP). A comparative study was conducted on 40 yoganaïve subjects and 40 yoga practitioners with an average age of 31.08 ± 7.31 years and 29.93 ± 7.57 years, respectively. Heart rate variability, blood pressure variability, baroreflex sensitivity, and correlation between systolic blood pressure and RR interval were evaluated at rest and during LBNP. In yoga practitioners, the heart rate was lower in supine rest (p = 0.011) and during LBNP (p = 0.043); the pNN50 measure of heart rate variability was higher in supine rest (p = 0.011) and during LBNP (p = 0.034). The yoga practitioners' standard deviation of successive beat-to-beat blood pressure intervals of systolic blood pressure variability was lower in supine rest (p = 0.034) and during LBNP (p = 0.007), with higher sequence baroreflex sensitivity (p = 0.019) and ~ high-frequency baroreflex sensitivity. Mean systolic blood pressure and RR interval were inversely correlated in the yoga group (r = -0.317, p = 0.049). The yoga practitioners exhibited higher parasympathetic activity and baroreflex sensitivity with lower systolic blood pressure variability, indicating better adaptability to LBNP compared to the yoga-naïve group. Our findings indicate that the yoga module was helpful in conditions of hypovolemia in healthy subjects; it is proposed to be beneficial in clinical conditions associated with sympathetic dominance, impaired barore-flex sensitivity, and orthostatic intolerance.

Aerobic or resistance training improves autonomic control of circulation in oophorectomized rats with cardiometabolic dysfunctions: Impact on renal oxidative stress.

Cardiovascular autonomic dysfunction is associated with end organ damage and increased risk of mortality. Menopause and metabolic syndrome increase the risk for cardiorenal complications. In this study, we investigated the effects of aerobic or resistance exercise training on autonomic control of circulation and renal oxidative stress in a model of menopause and metabolic syndrome. Female Wistar rats and spontaneously hypertensive rats (SHR) were divided into 5 groups (n = 8): control (C), hypertensive (H), and sedentary (FHO), aerobic trained (FHOTa) and resistance trained (FHOTr) oophorectomized hypertensive treated with fructose (100 mg/mL drink water for 19 weeks). The FHO group presented increased vascular sympathetic modulation (LF-SBP), impaired baroreflex sensitivity (BRS) associated with increased blood pressure (BP) when compared to the H group. Aerobic exercise training enhanced tachycardic responses, while resistance training improved bradycardic responses to BP changes, thus ameliorating BRS. Moreover, despite unchanged BP, both exercise training protocols were effective in preventing increase in LF-SBP, reduction in systemic nitric oxide bioavailability (NOx), and increase in oxidative stress in the renal tissue, by decreasing lipid and protein oxidation in renal tissue. Positive correlation between LF-SBP and renal lipoperoxidation (r = 0.63, p < 0.05), as well as a negative correlation between NOx and renal lipoperoxidation (r = -0.66, p < 0.05) were observed. In conclusion, both aerobic and resistance exercise training were effective in improving autonomic control of circulation and reducing renal oxidative stress, thus attenuating the deleterious effects induced by arterial hypertension and fructose overload in female rats after ovarian hormone deprivation.

The protective role of SOD1 overexpression in central mediation of bradycardia following chronic intermittent hypoxia in mice.

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is associated with many cardiovascular complications. Similar to OSA, chronic intermittent hypoxia (CIH) (a model for OSA) leads to oxidative stress and impairs baroreflex control of the heart rate (HR) in rodents. The baroreflex arc includes the aortic depressor nerve (ADN), vagal efferent, and central neurons. In this study, we used mice as a model to examine the effects of CIH on baroreflex sensitivity, aortic baroreceptor afferents, and central and vagal efferent components of the baroreflex circuitry. Furthermore, we tested whether human Cu/Zn Superoxide Dismutase (SOD1) overexpression in transgenic mice offers protection against CIH-induced deficit of the baroreflex arc. Wild-type C57BL/6J and SOD1 mice were exposed to room air (RA) or CIH and were then anesthetized, ventilated, and catheterized for measurement of mean arterial pressure (MAP) and HR. Compared with wild-type RA control, CIH impaired baroreflex sensitivity but increased maximum baroreceptor gain and bradycardic response to vagal efferent stimulation. Additionally, CIH reduced the bradycardic response to ADN stimulation, indicating a diminished central regulation of bradycardia. Interestingly, SOD1 overexpression prevented CIH-induced attenuation of HR responses to ADN stimulation and preserved HR responses to vagal efferent stimulation in transgenic mice. We suggest that CIH decreased central mediation of the baroreflex and SOD1 overexpression may prevent the CIH-induced central deficit.