Sympathetic Baroreflex Sensitivity Research Articles

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.

Spontaneous Sympathetic Baroreflex Sensitivity Is Impaired in Patients with Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have chronic overactivation of the sympathetic nervous system that contributes to hypertension and increased cardiovascular risk. The sympathetic baroreflex is a major regulator of sympathetic activity in response to changes in blood pressure; however, limited information is available regarding sympathetic baroreflex control in non-dialysis patients with CKD. In the present study we tested the hypothesis that baroreflex control of muscle sympathetic nerve activity (MSNA) is attenuated in non-dialysis patients with CKD. In 17 sedentary patients with CKD stages III-IV (76% hypertensive and 29% with diabetes) [12 male/5 female, age: 57 ± 13 yr, 13 Black/4 White, systolic/diastolic BP: 122 ± 17/75 ± 7 mmHg, BMI: 31 ± 5 kg/m2, eGFR: 40 ± 14 mL/min/1.73m2] and 9 controls (CON) (89% hypertensive and 22% with diabetes) [7 male/2 female, age: 51 ± 13 yr, 8 Black/1 White, systolic/diastolic BP: 123 ± 6/79 ± 6 mmHg, BMI: 30 ± 6 kg/m2, eGFR: 95 ± 12 mL/min/1.73m2], resting beat-to-beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and muscle sympathetic nerve activity (MSNA, microneurography) were continuously recorded during 10 min of semi-recumbent rest. Weighted linear regression analysis between MSNA burst incidence and diastolic blood pressure was used to determine the spontaneous sympathetic baroreflex sensitivity (sBRS). Resting MSNA burst incidence was higher in patients with CKD [CKD: 70 ± 19 bursts (100 heart beats)−1. mmHg−1 versus CON: 47 ± 9 bursts (100 heart beats)−1. mmHg−1; p<0.001], and a higher MSNA burst frequency was observed in CKD (CKD: 43 ± 11 bursts. min−1 versus CON: 32 ± 10 bursts. min−1; P=0.021], whereas resting mean arterial blood pressure (91 ± 9 mmHg versus 94 ± 5 mmHg; P=0.317) and heart rate were similar between groups. Patients with CKD had reduced sBRS compared to controls [CKD: -1.37 ± 0.59 bursts (100 heart beats)−1 mmHg−1 versus CON: -2.79 ± 1.33 bursts (100 heart beats)−1 mmHg−1; P=0.013]. The MSNA burst incidence (r = -0.63, p<0.001) and the sBRS (r = -0.57, P=0.002) were significantly associated with the estimated glomerular filtration rate (eGFR). Overall, these preliminary findings suggest an attenuated sympathetic baroreflex sensitivity in patients with CKD compared with age and-comorbidities matched controls, with greater impairment in those with more severe kidney dysfunction. This work was supported by National Institutes of Health Grants R01HL135183 and R61AT010457 (J.P). 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.

Sympathetic Neural Control at Rest and During the Cold Pressor Test in Patients With Heart Failure With Preserved Ejection Fraction.

We tested the hypothesis that patients with heart failure with preserved ejection fraction (HFpEF) would have greater muscle sympathetic nerve activity (MSNA) at rest and sympathetic reactivity during a cold pressor test compared with non-heart failure controls. Further, given the importance of the baroreflex modulation of MSNA in the control of blood pressure (BP), we hypothesized that patients with HFpEF would exhibit a reduced sympathetic baroreflex sensitivity. Twenty-eight patients with HFpEF and 44 matched controls (mean±SD: 71±8 versus 70±7 years; 9 men/19 women versus 16 men/28 women) were studied. BP, heart rate, and MSNA (microneurography) were measured during 6 to 10 minutes of supine rest and the 2-minute cold pressor test. Spontaneous sympathetic baroreflex sensitivity was assessed during supine rest. Patients with HFpEF had higher resting MSNA burst frequency (39±14 versus 31±12 bursts/min; P=0.020) and lower sympathetic baroreflex sensitivity (-2.83±0.76 versus -3.57±1.19 bursts/100 heartbeats/mm Hg; P=0.019) than controls, but burst incidence was not different between groups (56±19 versus 50±20 bursts/100 heartbeats; P=0.179). During the cold pressor test, increases in MSNA indices did not differ between groups (P=0.135-0.998), but patients had a smaller increase in diastolic BP (Δ4±6 versus Δ14±11 mm Hg; P<0.001) compared with controls. Despite augmented resting MSNA burst frequency, burst incidence was not significantly different between groups, and sympathetic baroreflex sensitivity was reduced in patients with HFpEF. Furthermore, patients had preserved sympathetic reactivity but attenuated diastolic BP responses during the cold pressor test. These data suggest that, during physiological stress, sympathetic reactivity is intact, but the peripheral pathway for sympathetic vasoconstriction may be impaired in HFpEF.

762 - Spontaneous sympathetic baroreflex sensitivity is impaired in patients with chronic kidney disease

762 - Spontaneous sympathetic baroreflex sensitivity is impaired in patients with chronic kidney disease

Reduced resting beat-to-beat blood pressure variability in females with relapsing-remitting multiple sclerosis

BackgroundRelapsing-remitting multiple sclerosis (RRMS) is a demyelinating disease of the central nervous system and cardiovascular autonomic dysfunction has been well documented in this population. The sympathetic nervous system contributes to beat-to-beat blood pressure regulation primarily by baroreflex control of the peripheral vasculature which may be impaired in females with RRMS. Even at rest, attenuated sympathetic control of vasomotor tone may result in large and frequent blood pressure excursions (i.e., greater blood pressure variability). Therefore, the primary purpose of this investigation was to test the following hypotheses; (1) females with RRMS have augmented beat-to-beat blood pressure variability compared to healthy controls and (2) reduced sympathetic baroreflex sensitivity in females with RRMS is related to augmented blood pressure variability. MethodsElectrocardiogram and beat-to-beat blood pressure were continuously recorded during 8–10 min of supine rest in 26 females with clinically definite RRMS and 24 sex-, age- and BMI- matched healthy controls. Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (MS, n = 15; CON, n = 14). Traditional statistical measurements of dispersions were used to index beat-to-beat blood pressure variability. Spontaneous sympathetic baroreflex sensitivity was quantified by sorting diastolic blood pressures into 3 mmHg bins and calculating MSNA burst incidence within each bin. Weighted linear regression was then used to account for the number of cardiac cycles in each bin and calculate slopes. Spontaneous cardiac baroreflex sensitivity was determined using the sequence method. ResultsGroups had similar resting mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), MSNA burst frequency and MSNA burst incidence (All P > 0.05). The standard deviation and interquartile range of MAP, SBP and DBP were less in females with RRMS compared to healthy controls (All P < 0.05). There were no between groups differences in sympathetic baroreflex sensitivity or cardiac baroreflex sensitivity (Both P > 0.05) and baroreflex sensitivity measures were not related to any indices of blood pressure variability (Both P > 0.05). ConclusionThese data suggest that females with RRMS have reduced beat-to-beat blood pressure variability. However, this does not appear to be related to changes in sympathetic or cardiac baroreflex sensitivity.

Glucose metabolism and autonomic function in healthy individuals and patients with type 2 diabetes mellitus at rest and during exercise.

Autonomic dysfunction is a common complication of type 2 diabetes mellitus (T2DM). However, the character of dysfunction varies in different reports. Differences in measurement methodology and complications might have influenced the inconsistent results. We sought to evaluate comprehensively the relationship between abnormal glucose metabolism and autonomic function at rest and the response to exercise in healthy individuals and T2DM patients. We hypothesized that both sympathetic and parasympathetic indices would decrease with the progression of abnormal glucose metabolism in individuals with few complications related to high sympathetic tone. Twenty healthy individuals and 11 T2DM patients without clinically evident cardiovascular disease other than controlled hypertension were examined. Resting muscle sympathetic nerve activity (MSNA), heart rate variability, spontaneous cardiovagal baroreflex sensitivity (CBRS), sympathetic baroreflex sensitivity and the MSNA response to handgrip exercise were measured. Resting MSNA was lower in patients with T2DM than in healthy control subjects (P=0.011). Resting MSNA was negatively correlated with haemoglobin A1c in all subjects (R=-0.45, P=0.024). The parasympathetic components of heart rate variability and CBRS were negatively correlated with glycaemic/insulin indices in all subjects and even in the control group only (all, P<0.05). In all subjects, the MSNA response to exercise was positively correlated with fasting blood glucose (R=0.69, P<0.001). Resting sympathetic activity and parasympathetic modulation of heart rate were decreased in relationship to abnormal glucose metabolism. Meanwhile, the sympathetic responses to handgrip were preserved in diabetics. The responses were correlated with glucose/insulin parameters throughout diabetic and control subjects. These results suggest the importance of a comprehensive assessment of autonomic function in T2DM.

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.

Age- and sex-related differences in sympathetic vascular transduction and neurohemodynamic balance in humans.

Bursts of muscle sympathetic nerve activity (MSNA) and the ensuing vasoconstriction are pivotal determinants of beat-by-beat blood pressure regulation. Although age and sex impact blood pressure regulation, how these factors affect the central and peripheral arcs of the baroreflex remains unclear. In 27 young [25 (SD 3) yr] males (YM; n = 14) and females (YF; n = 13) and 23 older [71 (SD 5) yr] males (OM; n = 11) and females (OF; n = 12), femoral artery blood flow, blood pressure, and MSNA were recorded for 10 min of supine rest. Sympathetic baroreflex sensitivity (i.e., central arc) was quantified as the relationship between diastolic blood pressure and MSNA burst incidence. Signal averaging was used to determine sympathetic vascular transduction into leg vascular conductance (LVC) for 12 cardiac cycles following MSNA bursts (i.e., peripheral arc). Older adults demonstrated attenuated sympathetic transduction into LVC (both P < 0.001) following MSNA bursts, and smaller increases in sympathetic transduction as a function of MSNA burst size and firing pattern compared with young adults (range, P = 0.004-0.032). YM (r2 = 0.36; P = 0.032) and OM (r2 = 0.51; P = 0.014) exhibited an inverse relationship between the central and peripheral arcs of the baroreflex, whereas females did not (YF, r2 = 0.03, P = 0.621; OF, r2 = 0.06, P = 0.445). MSNA burst incidence was inversely related to sympathetic transduction in YM and OF (range, P = 0.03-0.046) but not in YF or OM (range, P = 0.360-0.603). These data indicate that age is associated with attenuated sympathetic vascular transduction, whereas age- and sex-specific changes are present in the relationship between the central and peripheral arcs of the baroreflex regulation of blood pressure.NEW & NOTEWORTHY Sympathetic vascular transduction is attenuated in older compared with young adults, regardless of biological sex. Males, but not females (regardless of age), demonstrate an inverse relationship between central (sympathetic baroreflex sensitivity) and peripheral (sympathetic vascular transduction) components of the baroreflex arc. Young males and older females exhibit an inverse relationship between resting sympathetic outflow and sympathetic vascular transduction. Our results indicate that age and sex exert independent and interactive effects on sympathetic vascular transduction and sympathetic neurohemodynamic balance in humans.

Decentering and baroreflex sensitivity in adults with elevated blood pressure

Previous studies have linked the ability to decenter, a non-judgmental view of emotions, with lower arterial stiffness and better nocturnal blood pressure dipping in adults. It is unknown however if autonomic regulation of blood pressure is linked to decentering. Therefore, the purpose of this study was to determine if decentering ability is related to cardiovagal or sympathetic baroreflex sensitivity. Thirty-three adults (age 25±6 years; BMI 25±3 kg/m2) with resting blood pressure ≥120/80 mmHg volunteered for this study. All participants had a BMI &lt;30 kg/m2, and had no history of smoking, diabetes, or prescriptions for blood pressure or cardiac function. Participants completed an 11-item experiences questionnaire to evaluate decentering, and then were equipped for a supine autonomic evaluation. The autonomic evaluation included continuous recording of heart rate via 3-lead ECG, muscle sympathetic nerve activity (MSNA) via microneurography, and beat-to-beat blood pressure via finger photoplethysmography. Cardiovagal baroreflex sensitivity (n=33) included estimation of vagal activation by evaluating up-up relationships between systolic arterial pressure (SAP) and R-R intervals of the ECG. Vagal withdrawal was also estimated via the down-down relationships between SAP and R-R intervals. Spontaneous sympathetic baroreflex sensitivity (n=26) was evaluated by evaluating the relationship between changes in diastolic arterial pressure (DAP) in 3 mmHg bins vs. changes in MSNA burst incidence (i.e., bursts / 100 heart beats). Results from 2-tailed Pearson correlation analyses revealed that there was not a relationship between decentering and vagal activation (r=-0.07; p=0.71) or between decentering and vagal withdrawal (r=-0.28; p=0.12). Likewise, there was no relationship between decentering and sympathetic baroreflex sensitivity (r=0.10; p=0.64). Our findings suggest that there is not a clear link between decentering and autonomic regulation of blood pressure as estimated through both cardiovagal and baroreflex sensitivity. NIH (1R15HL140596-01); Nils K. Nelson Endowment Fund 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.

Evening but not Morning Aerobic-Training Improves Sympathetic Nerve Activity and Sympathetic Baroreflex Sensitivity in Treated Hypertension: A Randomized Clinical Trial

Background: A previous study demonstrated that the blood pressure (BP)-lowering effect is potentiated when aerobic exercise training is conducted in the evening than in the morning in medicated people with hypertension. Additionally, this greater reduction in BP occurred concomitantly with a greater decrease in sympathetic vasomotor modulation evaluated by BP variability, which suggests a greater effect of evening training on sympathetic autonomic regulation. However, this hypothesis still needs to be using direct measures. Objective: To compare the effect of 10 weeks of aerobic training conducted in the morning (MT) with the same training conducted in the evening (ET) on muscle sympathetic nerve activity (MSNA) and sympathetic baroreflex sensitivity (BRS) in treated hypertension. Methods: This randomized clinical trial was conducted in a single-center with a parallel-group design. Twenty-three older patients with treated hypertension (12 males, 67±6 y) were randomly allocated into training in the MT group (7-10 AM) (n=12) or in the ET group (5-8 PM) (n=11). The aerobic training consisted of cycling 3 times/week for 45 min at moderate intensity. Before and after 10 weeks of training, sympathetic BRS was evaluated across the extensive range of the reflex arc by eliciting rapid changes in BP induced by sequential bolus injections of nitroprusside for 1 min followed by phenylephrine for 2 min (modified-Oxford technique). We continuously record beat-to-beat BP (finger photoplethysmography), heart rate (electrocardiography), and MSNA (fibular nerve microneurography). Sympathetic BRS was quantified the weighted negative linear regression slope between diastolic BP (3 mmHg bin) and MSNA burst incidence [(bursts/100 heartbeats)/mmHg]. Two-way mixed ANOVAs were employed with significance set as P≤0.05. Results: Systolic BP decreased after ET but not after MT (-13 [95% CI = -25 to -2] vs. -1 [95% CI = -8 to +6] mmHg, P=0.04), respectively, while diastolic BP decreased similarly in both groups. MSNA incidence decreased greater after ET than MT (-12 [95% CI = -16 to -9] vs. -3 [95% CI = -10 to +4] bursts/100bpm, P=0.01). Sympathetic BRS improved only after ET but not after MT (-0.8 [95% CI = -1.3 to -0.3] vs. 0 [95% CI = -0.7 to +0.7] bursts/100bpm/mmHg, P=0.01). Conclusion: In older adults with hypertension receiving antihypertensive medication, 10 weeks of aerobic training conducted at both times of day decreases diastolic BP while only the aerobic training conducted in the evening improves systolic BP, MSNA incidence, and sympathetic BRS. FAPESP: 2018/05226-0; CNPQ 304436/2018-6; OHSU Fellowship for Diversity in Research. 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.

Posture-related changes in sympathetic baroreflex sensitivity during normal pregnancy.

Normal pregnancy is associated with vast adjustments in cardiovascular autonomic control. Sympathetic baroreflex sensitivity has been reported to be attenuated during pregnancy in animal models, but most studies in humans are cross-sectional and findings from longitudinal case studies are inconclusive. It remains unclear how sympathetic baroreflex sensitivity is altered longitudinally during pregnancy within an individual in different body postures. Therefore, this study examined the impact of posture on sympathetic baroreflex sensitivity in 24 normal-weight normotensive pregnant women. Spontaneous sympathetic baroreflex sensitivity was assessed during early (6-11weeks) and late (32-36weeks) pregnancy and 6-10weeks postpartum in the supine posture and graded head-up tilt (30° and 60°). In addition, data from the postpartum period were compared with (and no different to) 18 age-matched non-pregnant women to confirm that the postpartum period was reflective of a non-pregnant condition (online supplement). When compared with postpartum (-3.8 ± 0.4bursts/100heartbeats/mmHg), supine sympathetic baroreflex sensitivity was augmented during early pregnancy (-5.9 ± 0.4bursts/100heartbeats/mmHg, P < 0.001). However, sympathetic baroreflex sensitivity at 30° or 60° head-up tilt was not different between any phase of gestation (P > 0.05). When compared to supine, sympathetic baroreflex sensitivity at 60° head-up tilt was significantly blunted during early (Δ2.0 ± 0.7bursts/100 heartbeats/mmHg, P = 0.024) and late (Δ1.5 ± 0.6bursts/100heartbeats/mmHg, P = 0.049) pregnancy but did not change postpartum (Δ0.4 ± 0.6bursts/100heartbeats/mmHg, P = 1.0). These data show that time-course changes in sympathetic baroreflex sensitivity are dependent on the posture it is examined in and provides a foundation of normal blood pressure regulation during pregnancy for future studies in women at risk for adverse pregnancy outcomes.

Abstract 13228: Cannabis Inhalation Reduces Muscle Sympathetic Nerve Activity in Humans

Introduction: Despite widespread use, the neuro-cardiovascular responses associated with cannabis use remain incompletely understood. Acute increases in heart rate, which are abolished under beta-adrenoreceptor blockade, suggest cannabis increases cardiac sympathetic activity; however, its effects on peripheral sympathetic outflow have not been measured. The objective of this work was to quantify direct recordings of efferent post-ganglionic muscle sympathetic nerve activity (MSNA) following cannabis inhalation. Hypothesis: MSNA would be increased following cannabis inhalation. Methods: Blood pressure (BP), heart rate, and MSNA measured from the fibular nerve, were recorded in seventeen young, healthy participants (22±3y: 8F) for a 10-minute epoch before and after inhalation of aerosolized dry cannabis flower (100mg, 13.6% THC). Cardiac output was estimated from finger photoplethysmography (Modelflow method). Arterial baroreflex control of MSNA was quantified using the slope of the weighted linear regression between diastolic BP and MSNA. Results: Mean BP (79±7 vs. 84±8mmHg), heart rate (61±7 vs. 81±14bpm), cardiac output (4.8±1.1 vs. 6.8±2.5L/min), and total vascular conductance (50±11 vs. 71±26mL/min/mmHg) were increased, while MSNA burst frequency (17±7 vs. 8±6bursts/min), incidence (29±11 vs. 11±9bursts/100hb), and amplitude (38.6±6.4% vs. 23.8±8.3%), and sympathetic baroreflex sensitivity (-3.9±1.8 vs. -1.5±1.5bursts/100hb/mmHg) were decreased following cannabis inhalation (all P &lt;0.01). The rise in cardiac output was negatively associated with the reduction in MSNA burst frequency (r 2 =0.40; P &lt;0.01). Conclusions: These data demonstrate that MSNA is reduced following acute cannabis inhalation in humans and is mediated, in part, through a baroreflex mechanism.

Baroreflex responses to limb venous distension in humans.

The venous distension reflex (VDR) is a pressor response evoked by peripheral venous distension and accompanied by increased muscle sympathetic nerve activity (MSNA). The effects of venous distension on the baroreflex, an important modulator of blood pressure (BP), have not been examined. The purpose of this study was to examine the effect of the VDR on baroreflex sensitivity (BRS). We hypothesized that the VDR will increase the sympathetic BRS (SBRS). Beat-by-beat heart rate (HR), BP, and MSNA were recorded in 16 female and 19 male young healthy subjects. To induce venous distension, normal saline equivalent to 5% of the forearm volume was infused into the veins of the occluded forearm. SBRS was assessed from the relationship between diastolic BP and MSNA during spontaneous BP variations. Cardiovagal BRS (CBRS) was assessed with the sequence technique. Venous distension evoked significant increases in BP and MSNA. Compared with baseline, during the maximal VDR response period, SBRS was significantly increased (-3.1 ± 1.5 to -4.5 ± 1.6 bursts·100 heartbeats-1·mmHg-1, P < 0.01) and CBRS was significantly decreased (16.6 ± 5.4 to 13.8 ± 6.1 ms·mmHg-1, P < 0.01). No sex differences were observed in the effect of the VDR on SBRS or CBRS. These results indicate that in addition to its pressor effect, the VDR altered both SBRS and CBRS. We speculate that these changes in baroreflex function contribute to the modulation of MSNA and BP during limb venous distension.

Potentiation of GABAergic synaptic transmission by diazepam acutely increases resting beat‐to‐beat blood pressure variability in young adults

IntroductionResting beat‐to‐beat blood pressure (BP) variability is a powerful predictor of cardiovascular events and end‐organ damage. Recent studies indicate that resting beat‐to‐beat BP variability possesses greater prognostic value when compared with traditional 24‐h ambulatory or home‐based BP monitoring. However, despite the well‐recognized clinical significance of resting beat‐to‐beat BP variability, its underlying mechanisms remain incompletely understood. The sympathetic nervous system is critical for BP regulation. Given that the sympathetic pre‐motor neurons are highly regulated by inhibitory GABAergic interneurons, it is reasonable to speculate that GABA receptors may contribute to the beat‐to‐beat BP variability. However, this hypothesis has not been tested experimentally before. Therefore, in this study, we tested the hypothesis that a potentiation of GABAergic synaptic transmission by diazepam would acutely increase resting beat‐to‐beat blood pressure variability in humans.MethodsIn 40 (17 females) young, normotensive adults, resting beat‐to‐beat BP (finger photoplethysmography) was continuously measured for 5‐10 min, 60 min after the oral administration of either diazepam (10 mg) or placebo. The experiments were conducted in a randomized, double‐blinded, placebo‐controlled and crossover design. Stroke volume was estimated from the BP waveform (ModelFlow) permitting the calculation of cardiac output (CO) and total peripheral resistance (TPR). Parameters of variability included the standard deviation, range, interquartile range (the difference between the 25th and 75th percentiles within‐subject), the coefficient of variation [(SD/mean) x 100], and the average real variability. Additionally, direct recordings of muscle sympathetic nerve activity (MSNA, microneurography) were obtained in a subset of subjects (n=13) and the gain of arterial baroreflex control of MSNA (sympathetic baroreflex) and heart rate (cardiac baroreflex), as well as signal‐averaged sympathetic transduction of blood pressure calculated.ResultsCompared to placebo, diazepam significantly increased the standard deviation of systolic (4.7 ± 1.4 vs. 5.7 ± 1.5 mmHg, P = 0.001), diastolic (3.8 ± 1.2 vs. 4.5 ± 1.2 mmHg, P = 0.007) and mean BP (3.8 ± 1.1 vs. 4.5 ± 1.1 mmHg, P = 0.002), as well as CO (469 ± 149 vs. 626 ± 259 ml/min, P &lt; 0.001) and TPR (1.0 ± 0.3 vs. 1.4 ± 0.6 mmHg/l/min, P &lt; 0.001). Similar results were found using all indices of variability. Furthermore, diazepam reduced resting MSNA burst frequency (placebo: 22 ± 6 bursts/min vs. diazepam: 18 ± 8 bursts/min, P = 0.025) without affecting cardiac or sympathetic baroreflex sensitivity. However, the peak increase in mean BP following a spontaneous burst of MSNA (i.e., sympathetic transduction) was accentuated after diazepam administration.ConclusionThis is the first study to indicate that GABAA receptors may play a role in resting beat‐to‐beat BP variability. These findings advance our current understanding of the neural network mechanisms contributing to the resting beat‐to‐beat BP variability in young adults.

The feasibility of baroreflex sensitivity measurements in heart failure subjects: The role of slow-patterned breathing.

Increased muscle sympathetic nerve activity (MSNA) indicates an adverse outcome in heart failure. Decreased baroreflex modulation of MSNA is a well-known feature of the disease. The determinability of cardiovagal baroreflex sensitivity (BRS) in heart failure is low, however, the determinability of sympathetic BRS is not known. We have assessed the spontaneous, MSNA burst incidence-based baroreflex index (BRSsymp) in 33 stable heart failure patients and in 10 healthy controls using the traditional r ≥ .5 cutoff for acceptable individual diastolic pressure-burst incidence slopes, and also a more stringent r ≥ .7 cutoff. We have also assessed the influence of 6/min breathing. The determinability of BRSsymp in heart failure patients was 64% during spontaneous breathing with r ≥ .5 cutoff, and 39% using the r ≥ .7 cutoff. The determinability of these indices further decreased during 6/min breathing, dropping to 29% with the r ≥ .7 cutoff. In contrast, the determinability of the cardiovagal BRS indices increased significantly with 6/min breathing (from 24% to 66%; p < .001). Patients who still had determinable BRSsymp at the r ≥ .7 cutoff had a significantly lower baseline burst incidence than those with an undeterminable index (70 ± 14 vs. 89 ± 10 burst/100 cycles; p < .002). Neither the 6/min breathing, nor the r ≥ .7 cutoff limit influenced the high availability of BRSsymp in healthy subjects. The determinability of BRSsymp in heart failure patients is limited, especially with the 0.7 limit for correlation. Undeterminable BRSsymp in patients is associated with higher sympathetic activity. 6/min breathing improves the determinability of cardiovagal BRS indices, but not that of BRSsymp.

Potentiation of GABAergic synaptic transmission by diazepam acutely increases resting beat-to-beat blood pressure variability in young adults.

Resting beat-to-beat blood pressure variability is a powerful predictor of cardiovascular events and end-organ damage. However, its underlying mechanisms remain unknown. Herein, we tested the hypothesis that a potentiation of GABAergic synaptic transmission by diazepam would acutely increase resting beat-to-beat blood pressure variability. In 40 (17 females) young, normotensive subjects, resting beat-to-beat blood pressure (finger photoplethysmography) was continuously measured for 5-10 min, 60 min after the oral administration of either diazepam (10 mg) or placebo. The experiments were conducted in a randomized, double-blinded, and placebo-controlled design. Stroke volume was estimated from the blood pressure waveform (ModelFlow) permitting the calculation of cardiac output and total peripheral resistance. Direct recordings of muscle sympathetic nerve activity (MSNA, microneurography) were obtained in a subset of subjects (n = 13), and spontaneous cardiac and sympathetic baroreflex sensitivity were calculated. Compared with placebo, diazepam significantly increased the standard deviation of systolic blood pressure (4.7 ± 1.4 vs. 5.7 ± 1.5 mmHg, P = 0.001), diastolic blood pressure (3.8 ± 1.2 vs. 4.5 ± 1.2 mmHg, P = 0.007), and mean blood pressure (3.8 ± 1.1 vs. 4.5 ± 1.1 mmHg, P = 0.002), as well as cardiac output (469 ± 149 vs. 626 ± 259 mL/min, P < 0.001) and total peripheral resistance (1.0 ± 0.3 vs. 1.4 ± 0.6 mmHg/L/min, P < 0.001). Similar results were found using different indices of variability. Furthermore, diazepam reduced MSNA (placebo: 22 ± 6 vs. diazepam: 18 ± 8 bursts/min, P = 0.025) without affecting the arterial baroreflex control of heart rate (placebo: 18.6 ± 6.7 vs. diazepam: 18.8 ± 7.0 ms/mmHg, P = 0.87) and MSNA (placebo: -3.6 ± 1.2 vs. diazepam: -3.4 ± 1.5 bursts/100 Hb/mmHg, P = 0.55). Importantly, these findings were not impacted by biological sex. We conclude that GABAA receptors modulate resting beat-to-beat blood pressure variability in young adults.

Acute effects of sublingual nitroglycerin on cardiovagal and sympathetic baroreflex sensitivity.

The effects of nitroglycerin (glyceryl trinitrate, GTN) on baroreflex sensitivity (BRS) are incompletely understood. Moreover, there are no reports evaluating the acute responses in both the sympathetic BRS (SBRS) and the cardiovagal BRS (CBRS) to the administration of sublingual GTN. We hypothesized that sublingual GTN modulates both CBRS and SBRS. In 10 healthy subjects, beat-to-beat heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were recorded before and for 10 min after sublingual administration of GTN 0.4 mg. SBRS was evaluated from the relationship between spontaneous variations in diastolic BP and MSNA. CBRS was assessed with the sequence technique. These variables were assessed during baseline, during 3rd-6th min (post A), and 7th-10th min (post B) after GTN administration. Two min after GTN administration, MSNA increased significantly and remained significantly elevated during recording. Compared with baseline, CBRS decreased significantly (post A: 12.9 ± 1.6 to 7.1 ± 1.0 ms/mmHg, P < 0.05), whereas SBRS increased significantly (post A: 0.8 ± 0.2 to 1.5 ± 0.2 units·beat-1·mmHg-1, P < 0.05) with an upward shift of the operating point. There were no differences in these variables between posts A and B. A clinical dose of GTN increased MSNA rapidly through effects on both CBRS and SBRS. These effects should be kept in mind when nitrates are used to clinically treat chest pain and acute coronary syndromes and used as vasodilators in experimental settings.

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.

Interaction Between Baroreflex and Venous Distension Reflex in Healthy Humans

Prior reports have shown that that venous distension induced by saline infusion into the veins of an arterially occluded forearm significantly raises muscle sympathetic nerve activity (MSNA) and blood pressure (BP) via activating afferent nerves in the forearm in healthy humans. Thus, peripheral venous distension induces a systemic sympatho-excitatory reflex (venous distension reflex, VDR). The baroreflex is an important modulator of BP via regulating sympathetic and vagal tone. However, the relationship between the VDR and the baroreflex has not been examined. Thus, the purpose of this study was to examine the relationship between VDR and the cardiovagal baroreflex sensitivity (CBRS) or sympathetic baroreflex sensitivity (SBRS). We hypothesized that VDR activation affects the CBRS and SBRS. Beat-to-beat heart rate (HR), BP and MSNA were recorded in 35 (19 M, 16 F) young healthy subjects (27 ± 1 yrs.). After a short period when a forearm was arterially occluded, 5% forearm volume normal saline (~40-60 ml) was infused into the veins of the occluded forearm at a rate of 30 ml/min. Prior studies showed that the maximal MSNA and BP responses occurred during the period of 30 seconds before and 30 seconds after the end of the saline infusion (maximal VDR responses). Thus, hemodynamic variables, MSNA, SBRS and CBRS were assessed during baseline (5 min) and the maximal VDR response period (1 min). SBRS was evaluated by analyzing the relationship between spontaneous variations in diastolic BP and MSNA. CBRS was assessed with the sequence technique. Mean BP, HR and MSNA during the maximal VDR response period were significantly greater than those during resting baseline (Baseline to VDR; MBP, 83.9 ± 1.8 to 98.6 ± 2.5 mmHg; HR, 65.2 ± 1.5 to 68.0 ± 1.9 bpm; MSNA, 22.8 ± 1.6 to 32.7 ± 1.7 bursts･min-1; all P < 0.05). SBRS absolute value during VDR was significantly increased (-0.66 ± 0.07 to -1.41 ± 0.10 units･beat-1･mmHg-1, P < 0.05) and SBRS operating point was reset and upward shifted. CBRS during VDR was significantly decreased (Baseline to VDR; 16.6 ± 0.9 to 13.8 ± 1.0 ms･mmHg-1, P < 0.05). These results indicate that VDR activation increased SBRS with an upward shift of the operating point and decreased CBRS, as it also evoked significant sympatho-excitation. Augmented sympathetic activity and impaired baroreflex function are important prognostic factors in patients with cardiovascular diseases. Thus, further studies are needed to examine VDR in patients with cardiovascular diseases.

Androgen Effects on Baroreflex Sensitivity in Women with AE‐PCOS

Polycystic ovary syndrome (PCOS) is a reproductive endocrinopathy affecting approximately 10% of reproductive age women. Hyperandrogenism in women may be associated with increased sympathetic activity and impaired blood pressure (BP) regulation. Women with the Androgen-Excess PCOS (AE-PCOS) phenotype can have severe clinical metabolic and cardiovascular comorbidities, including elevated BP. We tested the hypothesis that androgen exposure in AE-PCOS increases BP and impairs BP regulation, as indexed by sympathetic baroreflex sensitivity (BRS). We measured BRS in 5 women with AE-PCOS (mean±SD, age=25±5 y; BMI=40±2 kg/m2) at Baseline (BSL), after 4 days of reproductive hormone suppression with a gonadotropin-releasing hormone (GnRH) antagonist (ANT, 250 μg/day) and 4 days of GnRH ant+testosterone (T, 5 mg/day). Before participating, subjects were screened to demonstrate insulin resistance using an oral glucose tolerance test (AUC=25949±11038 IU for insulin, AUC=23385±2561 mg/dl for glucose). Muscle sympathetic nerve activity (MSNA), expressed in bursts/100 heartbeat (Hb), and diastolic BP (DBP) were measured during the Modified Oxford technique, and sympathetic BR gain (MSNA/DBP) served as an index of sympathetic BRS. We also assessed integrated BR gain with forearm vascular resistance changes as a function of lower body negative pressure (LBNP). Reproductive hormone suppression decreased resting mean arterial pressure compared to BSL (114±10 mm Hg) under both ANT (107±2 mm Hg) and T conditions (106±9 mm Hg, P=0.04). Sympathetic BR gain during ANT was greater compared to BSL (-0.922±0.506 vs. -0.800±0.542 bursts/100 Hb/mm Hg, respectively), and gain was unaffected when androgens were reintroduced (T=-0.819±0.276 bursts/100 Hb, P=0.29). Integrated BRS during LBNP was unaffected by hormone treatment (BSL=0.911±0.653; ANT=0.794±0.967; T= 1.002±0.367 units/mm Hg). In obese, insulin resistant women with AE-PCOS, suppressing testosterone and estrogen (E2) improved arterial BR control of MSNA, while testosterone administration did not restore BR control. Thus, our initial hypothesis that T impairs baroreflex control of MSNA is not supported by these data but suggests that the continued suppression of E2 during ANT and ANT+T may play a more important role. The potential impact of E2 could be a promising clinical intervention and will be directly tested in our future studies.