Cardiac Baroreceptor Research Articles

Repetitive bout of controlled soccer heading does not alter heart rate variability metrics: A preliminary investigation.

There is elevated unease regarding how repetitive head impacts, such as those associated with soccer heading, contribute to alterations in brain function. This study examined the extent heart rate variability (HRV) and cardiac baroreceptor sensitivity (BRS) metrics are altered immediately following an acute bout of soccer heading. Seven male elite soccer players (24.1 ± 1.5 years) completed 40 successful soccer headers in 20-min. The headers were performed under controlled circumstances using a soccer ball launcher located 25 meters away and using an initial ball velocity of 77.5 ± 3.7 km/h (heading condition). An accelerometer (xPatch) on the right mastoid process quantified linear/rotational head accelerations. Participants also completed sham (body contact) and control (non-contact) sessions. A three-lead ECG and finger photoplethysmography characterized short-term spontaneous HRV/cardiac BRS, before and after each condition. The SCAT3 indexed symptom scores pre-post exposures to all three conditions. During the heading condition, cumulative linear and rotational accelerations experienced were 1,574 ± 97.9 g and 313,761 ± 23,966 rad/s2, respectively. Heart rate trended toward an increase from pre- to post-heading (p = 0.063), however HRV metrics in the time-domain (ps > 0.260) and frequency-domain (ps > 0.327) as well as cardiac BRS (ps > 0.144) were not significantly changed following all three conditions. Following the heading condition, SCAT3 symptom severity increased (p = 0.030) with a trend for symptom score augmentation (p = 0.078) compared to control and sham. Whereas, symptoms as measured by the SCAT3 were induced following an acute bout of controlled soccer heading, these preliminary findings indicate they were not accompanied by alterations to autonomic function. Ultimately, this demonstrates further research is needed to understand the physiological underpinnings of alterations in brain function occurring immediately after a bout of soccer heading and how these may, over time, contribute to long-term neurological impairments.

The reciprocal relationship between cardiac baroreceptor sensitivity and cerebral autoregulation during simulated hemorrhage in humans.

A reciprocal relationship between the baroreflex and cerebral autoregulation (CA) has been demonstrated at rest and in response to acute hypotension. We hypothesized that the reciprocal relationship between cardiac baroreflex sensitivity (BRS) and CA would be maintained during sustained central hypovolemia induced by lower body negative pressure (LBNP), and that the strength of this relationship would be greater in subjects with higher tolerance to this stress. Healthy young adults (n=51; 23F/28M) completed a LBNP protocol to presyncope. Subjects were classified as high tolerant (HT; completion of -60mmHg LBNP stage, ≥20-min) or low tolerant (LT; did not complete -60mmHg LBNP stage, <20-min). R-R intervals (RRI), systolic arterial pressure (SAP), mean arterial pressure (MAP), and middle cerebral artery velocity (MCAv) were measured continuously. Cardiac BRS was calculated in the time domain (ΔHR/ΔSAP) and frequency domain (RRI-SAP low frequency (LF) transfer function gain), and CA was calculated in the time domain (ΔMCAv/ΔMAP) and frequency domain (MAP-mean MCAv LF transfer function gain). There was a moderate relationship between cardiac BRS and CA for the group of 51 subjects in both the time (R=-0.54, P<0.0001) and frequency (R=0.61, P<0.001) domains; there was a stronger relationship in the HT group (R=0.73) compared to the LT group (R=0.31) in the frequency domain (P=0.08), but no difference between groups in the time domain (HT: R=-0.73 vs. LT: R=-0.63; P=0.27). These findings suggest that an interaction between BRS and CA may be an important compensatory mechanism that contributes to tolerance to simulated hemorrhage in young healthy adults.

Post-Acute Effect of SARS-CoV-2 Infection on the Cardiac Autonomic Function.

BackgroundRecent studies reported a long-lasting effect of COVID-19 infection that extends beyond the active disease and disrupts various body systems besides the respiratory system. The current study aims to investigate the post-acute effect of SARS-CoV-2 infection on cardiovascular autonomic activity, reactivity and sensitivity in patients who had the infection at least 3 months before.MethodsThis was a comparative cross-sectional observational study. Fifty-nine subjects were allocated into two groups, controls (n=31), who had no history of positive COVID-19 infection, and the post-COVID patients (n=28) who were recruited 3 to 8 months after testing positive for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR). Baseline cardiovascular autonomic activity was evaluated through recording of baseline heart rate variability (HRV), autonomic reactivity was determined through standard cardiovascular autonomic reflex tests (CART), and cardiac autonomic sensitivity was assessed through cardiac baroreceptor sensitivity (cBRS).ResultsHigher incidence of orthostatic hypotension was observed in post-COVID patients compared to controls (39.3% and 3.2%, respectively, p <0.001). Additionally, significantly reduced handgrip test, and heart rate response to head-up tilt was illustrated in the post-COVID group (p <0.001). About 85.7% of post-COVID participants had at least one abnormal cardiovascular reflex test (CART) compared to the control group (p <0.001). Although HRV parameters (TP, LF, HF, SDRR, RMSSD, pRR50), and the cBRS were numerically lower in the post-COVID-19 group, this did not reach the level of significance.ConclusionThe results of the present study are suggestive of altered cardiovascular reactivity in post-acute COVID patients and demand further investigation and longer term follow up.

Acute cardiac autonomic and haemodynamic responses to leg and arm isometric exercise.

Acute cardiovascular responses following a single session of isometric exercise (IE) have been shown to predict chronic adaptations in blood pressure (BP) regulation. It was hypothesised that exercises which recruit more muscle mass induce greater reductions in BP compared to exercises using smaller muscle mass. To test this hypothesis, the current study aimed to compare the acute haemodynamic and autonomic responses to a single session of isometric wall squat (IWS) and isometric handgrip (IHG) training. Twenty-six sedentary participants performed a single IWS and IHG session in a randomised cross-over design, with training composed of 4 × 2-min contractions, with 2-min rest, at 95 HRpeak and 30% MVC respectively. Haemodynamic and cardiac autonomic variables were recorded pre, during, immediately post, and 1-h post-exercise, with the change from baseline for each variable used for comparative analysis. During IWS exercise, there was a significantly greater increase in systolic BP (P < 0.001), diastolic BP (P < 0.001), mean BP (P < 0.001), heart rate (P < 0.001), and cardiac output (P < 0.001), and a contrasting decrease in baroreflex effectiveness index (BEI) and cardiac baroreceptor sensitivity (cBRS). In the 10-min recovery period following IWS exercise, there was a significantly greater reduction in systolic BP (P = 0.005), diastolic BP (P = 0.006), mean BP (P = 0.003), total peripheral resistance (TPR) (P < 0.001), BEI (P = 0.003), and power spectral density (PSD-RRI) (P < 0.001). There were no differences in any variables between conditions 1-h post exercise. Isometric wall squat exercise involving larger muscle mass is associated with a significantly greater post-exercise hypotensive response during a 10-min recovery window compared to smaller muscle mass IHG exercise. The significantly greater reduction in TPR may be an important mechanism for the differences in BP response.

Long-term heart transplant recipients: heart rate-related effects on augmented transfer function coherence during repeated squat-stand maneuvers in males.

Previous research has highlighted that squat-stand maneuvers (SSMs) augment coherence values within the cerebral pressure-flow relationship to ∼0.99. However, it is not fully elucidated if mean arterial pressure (MAP) leads to this physiological entrainment independently, or if heart rate (HR) and/or the partial pressure of carbon dioxide (Pco2) also have contributing influences. A 2:1 control-to-case model was used in the present investigation [participant number (n) = 40; n = 16 age-matched (AM); n = 16 donor control (DM); n = 8 heart transplant recipients (HTRs)]. The latter group was used to mechanistically isolate the extent to which HR influences the cerebral pressure-flow relationship. Participants completed 5 min of squat-stand maneuvers at 0.05 Hz (10 s) and 0.10 Hz (5 s). Linear transfer function analysis (TFA) examined the relationship between different physiological inputs (i.e., MAP, HR, and Pco2) and output [cerebral blood velocity (CBV)] during SSM; and cardiac baroreceptor sensitivity (BRS). Compared with DM, cardiac BRS was reduced in AM (P < 0.001), which was further reduced in HTR (P < 0.045). In addition, during the SSM, HR was elevated in HTR compared with both control groups (P < 0.001), but all groups had near-maximal coherence metrics ≥0.98 at 0.05 Hz and ≥0.99 at 0.10 Hz (P ≥ 0.399). In contrast, the mean HR-CBV/Pco2-CBV relationships ranged from 0.38 (HTR) to 0.81 (DM). Despite near abolishment of BRS and blunted HR following heart transplantation, long-term HTR exhibited near-maximal coherence within the MAP-CBV relationship, comparable with AM and DM. Therefore, these results show that the augmented coherence with SSM is driven by blood pressure, whereas elevations in TFA coherence as a result of HR contribution are likely correlational in nature.

The Reciprocal Relationship Between Cardiac Baroreceptor Sensitivity and Cerebral Autoregulation During Simulated Hemorrhage in Humans

Tolerance to reduced central blood volume (e.g., via hemorrhage) depends upon cardiovascular and cerebrovascular mediated compensatory mechanisms to preserve cerebral perfusion. Prior studies have demonstrated a reciprocal relationship between the arterial baroreflex and cerebral autoregulation (CA) at rest and in response to acute hypotension. It is unknown if this reciprocal relationship persists during progressive and sustained hypotension simulating hemorrhage. We hypothesized that the reciprocal relationship between cardiac baroreceptor sensitivity (BRS) and CA would be maintained during a simulated hemorrhage induced by maximal lower body negative pressure (LBNP), and that the strength of this relationship would be greater in subjects with higher tolerance to this stress. Healthy young adults (n=51; 23F/28M, 26 ± 4 y) completed a step-wise LBNP protocol until the onset of presyncope. Subjects were classified as high tolerant (HT) if they completed at least the -60 mmHg stage of LBNP (≥ 20-min), and low tolerant (LT) if they became presyncopal prior to completing the -60 mmHg stage of LBNP (< 20-min), as previously defined by our group. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), and middle cerebral artery velocity (MCAv) were measured continuously. The absolute change from baseline to presyncope (Δ) was calculated for each variable. Cardiac BRS was calculated as ΔHR divided by ΔMAP, and CA was calculated as ΔMCAv divided by ΔMAP. The relationship between BRS and CA was assessed with Pearson's correlation coefficients for the entire group of 51 subjects, and within the HT and LT sub-groups. Absolute change values for the hemodynamic responses were also compared between the two tolerance groups. By design, tolerance to LBNP was different between the groups (HT (n=30): 1775 ± 225 s vs. LT (n=21): 1184 ± 253 s; P<0.0001). Accordingly, HT subjects demonstrated a greater ΔSV (HT: -51 ± 17 ml vs. LT: -41 ± 13 ml; P=0.03) and a greater ΔHR (HT: +56 ± 17 bpm vs. LT: +34 ± 20 bpm; P<0.0001) in response to maximal LBNP. Interestingly, ΔMAP (HT: -18 ± 7 mmHg vs. LT: -19 ± 9 mmHg; P=0.51), ΔMCAv (HT: -17 ± 8 cm/s vs. LT: -19 ± 10 cm/s; P=0.52), BRS (HT: 4 ± 3 bpm/mmHg vs. LT: 3 ± 4 bpm/mmHg; P=0.24), and CA (HT: 1.2 ± 0.9 cm/s.mmHg-1 vs. LT: 1.5 ± 1.8 cm/s.mmHg-1; P=0.45) were similar between HT and LT subjects. In support of our hypothesis, there was a strong reciprocal relationship (R=0.77; P<0.0001) between BRS and CA in the group of 51 subjects. When independently assessing this relationship within each tolerance group, however, there was a stronger relationship in LT subjects (R=0.94; P<0.0001) compared to HT subjects (R=0.57; P<0.001). In support of our hypothesis, the reciprocal relationship between cardiac BRS and CA was maintained during sustained and progressive hypotension, but this relationship was stronger in subjects with lower tolerance to this stress. These findings suggest that despite a strong overall relationship in the interaction between BRS and CA, it may not be a primary compensatory mechanism that dictates tolerance to simulated hemorrhage in young healthy adults.

Effects of renal denervation on cardiovascular, metabolic and renal functions in streptozotocin-induced diabetic rats

Diabetes promotes renal sympathetic hyperactivity, autonomic imbalance, and cardiovascular and renal dysfunction. Bilateral renal denervation (BRD) has emerged as a treatment for diabetes; however, the mechanisms that underlie the beneficial effects of BRD are unknown. AimsThe present study evaluated the effects of BRD on autonomic, cardiovascular, metabolic, and renal function in streptozotocin-diabetic rats. Main methodsWistar rats were separated into three experimental groups: control (CTR), diabetic (DM), and diabetic that underwent BRD (DM BRD). BRD was performed two weeks after STZ-diabetes induction, the experiments were performed four weeks after DM induction. This study evaluated sympathetic vasomotor nerve activity in different territories (renal, lumbar and splanchnic), arterial baroreceptor reflex, metabolic and renal function. Key findingsBRD significantly reduced glycemia, glycosuria, albuminuria, and SGLT2 gene expression in the kidney in DM rats. Renal sympathetic nerve activity (rSNA) was significantly increased and splanchnic sympathetic nerve activity (sSNA) was significantly decreased in DM rats, without changes in lumbar sympathetic nerve activity (lSNA). BRD was able to normalize sSNA and significantly increase lSNA in DM rats compared to control rats. Additionally, cardiac baroreceptor sensitivity was impaired in DM rats, and BRD significantly improved baroreflex sensitivity. SignificanceOur data suggest that renal nerves play an important role in autonomic, cardiovascular, and renal dysfunction in STZ-DM rats. Thus, sympathetic renal hyperactivity should be considered a possible therapeutic target in diabetic patients.

Impairments in Blood Pressure Regulation and Cardiac Baroreceptor Sensitivity Among Patients With Heart Failure Supported With Continuous-Flow Left Ventricular Assist Devices.

Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation. Twelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30o and 60o. Heart rate and BP were monitored during cardiopulmonary exercise testing. Cardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved-but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing. Among patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078972.

Effects of high-intensity intervals and moderate-intensity exercise on baroreceptor sensitivity and heart rate variability during recovery.

Numerous studies have examined heart rate variability (HRV) and cardiac baroreceptor sensitivity (BRS) variables during recovery both acutely (under 3 h) and long-term (24, 48, and 72 h) postexercise. However, there is little literature examining HRV and BRS measures between these timepoints. Spontaneous short-term HRV and cardiac BRS measures were collected in 9 participants before and at zero, 1, 2, 4, 6, and 8 h after 3 separate conditions: moderate-intensity continuous exercise (MICE; 45 min at 50% heart rate reserve), high-intensity interval exercise (HIIE; 25 min including ten 1-min intervals at 85% heart rate reserve), and control (30 min quiet rest). HRV measures in the time domain were only affected immediately following HIIE and MICE at hour zero (all p < 0.043), whereas frequency-domain metrics were unaltered (all p > 0.102). These measures were highly consistent across the control day (all p > 0.420). Cardiac BRS was assessed via low-frequency (LF) gain, and revealed reductions following HIIE at hour zero (p < 0.012). Cardiac BRS LF gain remained consistent following MICE and control interventions (all p > 0.280). The common practice of waiting 12 to 24 h is overly conservative as the current findings demonstrate measures return to baseline at ∼60 min after exercise. Moreover, these metrics demonstrated high levels of within- and between-day reliability. Novelty Previously a 12-h minimum restriction from exercise was required before participation in HRV/BRS studies. Recovery from moderate-intensity exercise for HRV and BRS metrics was <60 min; whereas, high-intensity intervals led to alterations for approximately 60 min. Spontaneous HRV and cardiac BRS demonstrated high levels of within-day reproducibility.

Autonomic Abnormalities in Patients With Primary Sjogren's Syndrome - Preliminary Results.

Primary Sjögren’s syndrome (pSS) is an autoimmune disease affecting exocrine glands and extra-glandular organs. There are conflicting reports on the presence of autonomic dysfunction in pSS and no data are available on the functional status of sympathetic outflow to the vessels and baroreceptor [baroreflex sensitivity (BRS)] control mechanisms. We investigated the cardiac (cBRS) and sympathetic (sBRS) baroreceptor modulation in both time and frequency domains and the cardiovascular autonomic profile in pSS patients compared to healthy controls. Autonomic symptoms were quantified by the Composite Autonomic Symptom Scale (COMPASS31) three-item questionnaire. The EULAR Sjogren’s syndrome patient reported index (ESSPRI) questionnaire evaluated the magnitude of pSS clinical symptoms, i.e., fatigue, pain, and sicca symptoms. Electrocardiogram, beat-by-beat arterial pressure (AP) and respiratory activity were continuously recorded in 17 pSS patients and 16 healthy controls, while supine and during 75° head-up tilt. In seven patients and seven controls, muscle sympathetic nerve activity (MSNA) was measured. Spectrum analysis of RR variability provided markers of cardiac vagal modulation (HFRR nu) and sympatho-vagal balance [low frequency (LF)/high frequency (HF)]. The power of LF (0.1 Hz) oscillations of systolic arterial pressure (SAP) variability (LFSAP) evaluated the vasomotor response to sympathetic stimulation. Compared to controls, pSS patients scored higher in total COMPASS31 (p < 0.0001) and all ESSPRI subdomains (fatigue, p = 0.005; pain, p = 0.0057; dryness, p < 0.0001). Abnormal scialometry (<1.5 ml/15 min) and Schirmer tests (<5 mm/5 min) were found in pSS patients and salivary flow rate was negatively associated with ESSPRI dryness (p = 0.0014). While supine, pSS patients had lower SEQcBRS index of cardiac baroreceptor sensitivity, higher HFRRnu (p = 0.021), lower LF/HF (p = 0.007), and greater MSNA (p = 0.038) than controls. No differences were observed in LFSAP between groups. During orthostatic challenge, although LFSAP increased similarly in both groups, MSNA was greater in pSS patients (p = 0.003). At rest pSS patients showed lower cBR control and greater parasympathetic modulation. Furthermore, greater sympathetic nerve activity was observed in pSS patients while supine and in response to gravitational challenge. We hypothesized that such enhanced sympathetic vasoconstrictor activity might reflect an attempt to maintain blood pressure in a setting of likely reduced vascular responsiveness.

Role of infarct location and pre-existing depression on cardiac baroreceptor sensitivity in subacute ischemic stroke.

Reduced cardiac baroreceptor sensitivity (BRS) after acute stroke is associated with worse outcome. The underlying mechanisms of reduced BRS are unclear. We evaluated cross correlation BRS (xBRS) in 184 patients with suspected acute ischemic stroke within 72h of symptom onset. Among these patients, 22 had a transient ischemic attack (TIA) and 27 had a stroke mimic. Sixty-four age- and sex-matched ambulant control subjects without stroke were included. Compared with controls, xBRS was significantly lower in patients with ischemic stroke, TIA, and stroke mimics (4.6, 4.7, and 4.4, respectively, vs 6.6, p<0.01). There was no difference in xBRS between right and left hemispheric infarctions (4.3 vs 4.9, p=0.144), right and left insular infarctions (4.5 vs 5.3, p = 0.286), and insular infarction vs non-insular infarctions (4.7 vs 4.5, p=0.996). Stroke patients with pre-existing depression/use of antidepressant medication had lower xBRS values than stroke patients with normal mental health (2.9 vs 4.8, p<0.05). Control patients with depression also had lower xBRS compared to controls without depression (3.4 vs 5.9, p<0.01). Our results suggest that decreased xBRS in the subacute phase after stroke is not associated with infarct localization. We found preliminary evidence for an association between pre-existing depression and use of antidepressant medication, and decreased BRS.

Hippocampal subareas arranged in the dorsoventral axis modulate cardiac baroreflex function in a site-dependent manner in rats.

What is the central question of this study? Classically, areas of the brainstem are involved in the cardiac baroreceptor reflex. However, forebrain areas, such as the hippocampus, may also modulate the cardiac baroreflex function. What is the main finding and its importance? According to the hippocampal subarea recruited dorsoventrally, the baroreflex function can be either facilitated or inhibited. These results are according to the new topographical division proposed for the hippocampus, i.e. it can be divided into functionally and anatomically different regions along its dorsoventral axis. From a neuroanatomical point of view, we may split the hippocampal formation into the dorsal (DH) and ventral hippocampus (VH). Although the basic intrinsic circuitry of the hippocampus seems to be maintained throughout its longitudinal axis, dorsal and ventral portions connect differently with cortical and subcortical areas and express different gene patterns, being functionally distinct. Differential stimulation of the DH or VH can evoke either an increase or a decrease in blood pressure, heart rate and sympathetic activity. However, to the best of our knowledge, specific involvement of the hippocampus and its different subareas in the baroreflex function remains to be investigated. In the present work, therefore, we evaluated the involvement of hippocampal subareas arranged on the dorsoventral axis in cardiac baroreflex modulation. Our results suggest that inhibition of hippocampal subareas by CoCl2 , a calcium-dependent synaptic neurotransmission blocker, differentially affects baroreflex sensitivity; administration of CoCl2 into the DH increased cardiac baroreflex function, whereas it diminished cardiac baroreflex function when administered into the VH. In contrast, administration of CoCl2 into intermediate portions of the hippocampus did not affect the baroreflex response. Our findings suggest that the hippocampus influences baroreflex function according to the hippocampal subarea recruited dorsoventrally.

Increased Dietary Salt Changes Baroreceptor Sensitivity and Intrarenal Renin-Angiotensin System in Goldblatt Hypertension.

Renovascular hypertension (2-kidney 1-clip model (2K1C)) is characterized by renin-angiotensin system (RAS) activation. Increased Angiotensin II (AngII) leads to sympathoexcitation, oxidative stress, and alterations in sodium and water balance. The aim of this study was to evaluate whether a discrete increase in sodium chloride intake in 2K1C rats leads to changes in cardiovascular and autonomic function, oxidative stress, and renin angiotensin aldosterone system. After 4 weeks of induction of hypertension, rats were fed a normal sodium diet (0.4% NaCl) or a high-sodium diet (2% NaCl) for 2 consecutive weeks. Experiments were carried out for 6 weeks after clipping. Mean arterial pressure (MAP), renal sympathetic nerve activity (rSNA), arterial baroreflex control of rSNA, and heart rate (HR) were assessed. Thiobarbituric acid reactive substances and glutathione were measured as indicators of systemic oxidative stress. Angiostensin-converting enzyme (ACE), ACE2, and angiotensinogen were evaluated in clipped and unclipped kidneys as also urinary angiotensinogen and plasma renin activity. Angiotensinogen, plasma renin activity (PRA) and angiotensin-converting enzyme (ACE) and ACE2 in clipped and unclipped kidneys were evaluated. High-sodium diet did not change systemic oxidative stress, and basal values of MAP, HR, or rSNA; however, increased renal (-0.7±0.2 vs. -1.5±0.1 spikes/s/mm Hg) and cardiac (-0.9±0.14 vs. -1.5±0.14 bpm/mm Hg) baroreceptor reflex sensitivity in 2K1C rats. Although there was no alteration in PRA, a high-salt diet significantly decreased urinary angiotensinogen, ACE, and ACE2 expressions in the clipped and unclipped kidneys. Increased arterial baroreceptor control associated with a suppression of the intrarenal RAS in the 2K1C rats on high-salt diet provide a salt-resistant effect on hypertension and sympathoexcitation in renovascular hypertensive rats.

Medial prefrontal cortex TRPV1 channels modulate the baroreflex cardiac activity in rats.

The ventral portion of the medial prefrontal cortex (vMPFC) comprises the infralimbic (IL), prelimbic (PL) and dorsopenducular (DP) cortices. The IL and PL regions facilitate the baroreceptor reflex arc. This facilitatory effect on the baroreflex is thought to be mediated by vMPFC glutamatergic transmission, through NMDA receptors. The glutamatergic transmission can be modulated by other neurotransmitters, such as the endocannabinoids, which are agonists of the TRPV1 receptor. TRPV1 channels facilitate glutamatergic transmission in the brain. Thus, we hypothesized that TRPV1 receptors in the vMPFC enhance the cardiac baroreflex response. Stainless steel guide cannulae were bilaterally implanted into the vMPFC of male Wistar rats. Afterwards, a catheter was inserted into the femoral artery, for recording MAP and HR, and into the femoral vein for assessing baroreflex activation. Microinjections of the TRPV1 receptor antagonists capsazepine and 6-iodo-nordihydrocapsaicin (6-IODO) into the vMPFC reduced the cardiac baroreflex activity in unanaesthetized rats. Capsaicin microinjected into the vMPFC increased the cardiac baroreflex activity in unanaesthetized rats. When an ineffective dose of the TRPV1 receptor antagonist 6-IODO was used, the capsaicin-induced increase in the cardiac baroreflex response was abolished. The higher doses of capsaicin administered into the vMPFC after the ineffective dose of 6-IODO displaced the dose-response curve of the baroreflex parameters to the right, with no alteration in the maximum effect of capsaicin. The results of the present study show that stimulation of the TRPV1 receptors in the vMPFC increases the cardiac baroreceptor reflex response.

Cardiovascular and Neurophysiological Assessment of Guanethidine‐Induced Loss of Postganglionic Neurons in Male Sprague Dawley Rats

During postganglionic depletion there are a number of physiological compensatory mechanisms that maintain cardiovascular (CV) hemodynamic control. However, there is limited understanding at what point sympathetic noradrenergic postganglionic depletion results in changes to CV hemodynamics. To investigate these relationships two experimental paradigms were designed. Guanethidine was used to pharmacologically diminish the postganglionic sympathetic neurons. Rats received daily IP injections of vehicle or guanethidine (100 mg/kg/day) for either 5 or 11 days with an additional 20 day recovery period following respective treatments. Evaluations of conscious measures of heart rate (HR), blood pressure (BP), activity, temperature, cardiac baroreceptor (BR) responsiveness, urinalysis (for catecholamine metabolite, 3-methoxy-4-hydroxyphenylethylenglycol; MHPG) and pupillometry assessments were performed. Following 5 days of guanethidine/recovery, there was a decrease in creatinine-normalized urine MHPG levels compared to vehicle controls (47%); however no other parameter evaluated differed from vehicle. Interestingly, following 11 days of guanethidine/recovery, there was not only decreased urine MHPG levels (67%), but also significant decreases in systolic and mean BP (-9 and -5 mm Hg, respectively; p<0.05), decreases in the pupil/iris ratio (19%; p<0.05), and diminished BR-mediated reflex tachycardia responses during BR testing (p<0.05). These data suggest that there is a threshold of postganglionic depletion required to elicit changes in physiological CV parameters.

Relationship between cerebral blood flow and blood pressure in long-term heart transplant recipients.

Heart transplant recipients are at an increased risk for cerebral hemorrhage and ischemic stroke; yet, the exact mechanism for this derangement remains unclear. We hypothesized that alterations in cerebrovascular regulation is principally involved. To test this hypothesis, we studied cerebral pressure-flow dynamics in 8 clinically stable male heart transplant recipients (62±8 years of age and 9±7 years post transplant, mean±SD), 9 male age-matched controls (63±8 years), and 10 male donor controls (27±5 years). To increase blood pressure variability and improve assessment of the pressure-flow dynamics, subjects performed squat-stand maneuvers at 0.05 and 0.10 Hz. Beat-to-beat blood pressure, middle cerebral artery velocity, and end-tidal carbon dioxide were continuously measured during 5 minutes of seated rest and throughout the squat-stand maneuvers. Cardiac baroreceptor sensitivity gain and cerebral pressure-flow responses were assessed with linear transfer function analysis. Heart transplant recipients had reductions in R-R interval power and baroreceptor sensitivity low frequency gain (P<0.01) compared with both control groups; however, these changes were unrelated to transfer function metrics. Thus, in contrast to our hypothesis, the increased risk of cerebrovascular complication after heart transplantation does not seem to be related to alterations in cerebral pressure-flow dynamics. Future research is, therefore, warranted.

Activation of histamine H1 receptors in the nucleus tractus solitarii attenuates cardiac baroreceptor reflex function in rats

The nucleus tractus solitarii (NTS) is a central brainstem structure that plays an important role in regulating cardiovascular homeostasis. In this study, we examined whether H1 receptors in the NTS can control the baroreceptor reflex function by modulating synaptic transmission. Cardiac baroreceptor reflex function was assessed before and after the microinjection of 2-pyridylethylamine (10-25 nmol), a histamine H1 receptor-specific agonist, into the NTS of urethane-anaesthetized Wistar rats. The cardiovascular responses induced by l-glutamate microinjection into the NTS were also examined before and after the NTS administration of 2-pyridylethylamine. Nucleus tractus solitarii microinjections of 2-pyridylethylamine significantly inhibited the gain of the cardiac baroreceptor reflex and bradycardiac/depressor responses induced by l-glutamate microinjection into the NTS. These findings suggest that histamine H1 receptors regulate the cardiac baroreceptor reflex in a post-synaptic manner to inhibit barosensitive NTS neurons. Taken together with our previous findings, the present results provide further evidence that histamine may play a role within the NTS in regulating cardiovascular homeostasis.

Modulation of baroreceptor afferent terminal excitability and reflex responses by phospholipase D‐coupled metabotropic glutamate receptors

We have demonstrated glutamate released from clear synaptic‐like vesicles (SLVs) modulates mechanoreceptor excitability in Ia primary afferent endings of rat muscle spindles acting on phospholipase D‐linked metabotropic glutamate receptors (PLD‐mGluRs; Bewick et al. 2005 J. Physiol 562, 381‐). We have tested whether the SLVs in baroreceptor endings (Krauhs, 1979 J. Neurocytol. 8:401‐) show a similar mechanism that modulates both afferent discharge and reflex‐evoked responses. Baroreceptors were stimulated by ramp increases in arterial pressure while either afferent discharge or reflex changes in heart rate and sympathetic nerve activity were measured after superfusion of the aortic arch with either the PLD‐mGluR antagonist PCCG‐13 (20μM) or glutamate (10mM) in situ. PCCG‐13 decreased baroreceptor afferent activity by 35% (P&lt;0.05) and glutamate increased discharge by 42% (P&lt;0.05) relative to control levels. Cardiac baroreceptor reflex gain was was attenuated reversibly by PCCG‐13 by 51% from 2.8+0.4 bpm/mmHg (P&lt;0.05). Baroreceptor reflex‐mediated sympathoinhibition was also depressed. Glutamate applied to the aortic arch mimicked a baroreflex response. These data indicate autogenic glutamate release from baroreceptor terminals regulate afferent discharge through PLD‐mGluRs to modulate reflex cardiac and sympathomotor responses. MRC funded research.

Diet-induced obesity severely impairs myelinated aortic baroreceptor reflex responses

Diet-induced obesity (DIO) attenuates the arterial cardiac baroreceptor reflex, but the mechanisms and sites of action are unknown. This study tested the hypothesis that DIO impairs central aortic baroreceptor pathways. Normal chow control (CON) and high-fat-chow obesity-resistant (OR) and obesity-prone (OP) rats were anesthetized (inactin, 120 mg/kg) and underwent sinoaortic denervation. The central end of the aortic depressor nerve (ADN) was electrically stimulated to generate frequency-dependent baroreflex curves (5-100 Hz) during selective activation of myelinated (A-fiber) or combined (A- and C-fiber) ADN baroreceptors. A mild stimulus (1 V) that activates only A-fiber ADN baroreceptors induced robust, frequency-dependent depressor and bradycardic responses in CON and OR rats, but these responses were completely abolished in OP rats. Maximal activation of A fibers (3 V) elicited frequency-dependent reflexes in all groups, but a dramatic deficit was still present in OP rats. Activation of all ADN baroreceptors (20 V) evoked even larger reflex responses. Depressor responses were nearly identical among groups, but OP rats still exhibited attenuated bradycardia. In separate groups of rats, the reduced heart rate (HR) response to maximal activation of ADN A fibers (3 V) persisted in OP rats following pharmacological blockade of β(1)-adrenergic or muscarinic receptors, suggesting deficits in both parasympathetic nervous system (PNS) and sympathetic nervous system (SNS) reflex pathways. However, the bradycardic responses to direct efferent vagal stimulation were similar among groups. Taken together, our data suggest that DIO severely impairs the central processing of myelinated aortic baroreceptor control of HR, including both PNS and SNS components.

Surgical Approach for Aortic Coarctation Influences Arterial Compliance and Blood Pressure Control

Increased arterial stiffness is linked to hypertension in adults after surgical repair for coarctation of the aorta. We evaluated the influence of surgical approaches, namely, subclavian flap repair (SFR) and end-to-end anastomosis (EEA), on arterial stiffness, blood pressure, cardiac output, and cardiac baroreceptor function in a cohort of young children after coarctation repair to determine if the surgical approach influenced longer term blood pressure control. We measured pulse wave velocity in 21 children with a mean age of 5 years, after early (less than 6 months) coarctation repair (SFR, n = 11; EEA, n = 10), and compared these with 18 matched controls. Blood pressure was recorded on three occasions from the right arm. Cardiac output was recorded using a transthoracic bioimpedence technique. We measured spontaneous baroreceptor reflex sensitivity to evaluate whether increased arterial stiffness was associated with reduced aortic baroreflex sensitivity. Right arm systolic blood pressure (108.3 + or - 3.5 mm Hg SFR versus 97.8 + or - 2.9 mm Hg EEA, p = 0.03) and pulse wave velocity (6.0 + or - 0.2 ms(-1) SFR versus 5.2 + or - 0.2 ms(-1) EEA, p = 0.02) were significantly greater in the SFR compared with EEA group. Blood pressure and pulse wave velocity were also higher in the SFR group compared with controls. These differences were not demonstrated when comparing the EEA group with controls. There was no difference in stroke volume, spontaneous baroreceptor reflex sensitivity, or heart rate or blood pressure variability between the groups. Young children undergoing SFR have higher blood pressure and stiffer upper limb arteries compared with matched children undergoing EEA. Our data suggest that better longer-term cardiovascular outcome is to be expected with the EEA surgical approach.