Baroreflex Control Of Heart Rate Research Articles

Dynamic Assessment of Baroreflex Control of Heart Rate During Induction of Propofol Anesthesia Using a Point Process Method

In this article, we present a point process method to assess dynamic baroreflex sensitivity (BRS) by estimating the baroreflex gain as focal component of a simplified closed-loop model of the cardiovascular system. Specifically, an inverse Gaussian probability distribution is used to model the heartbeat interval, whereas the instantaneous mean is identified by linear and bilinear bivariate regressions on both the previous R-R intervals (RR) and blood pressure (BP) beat-to-beat measures. The instantaneous baroreflex gain is estimated as the feedback branch of the loop with a point-process filter, while the RR-->BP feedforward transfer function representing heart contractility and vasculature effects is simultaneously estimated by a recursive least-squares filter. These two closed-loop gains provide a direct assessment of baroreflex control of heart rate (HR). In addition, the dynamic coherence, cross bispectrum, and their power ratio can also be estimated. All statistical indices provide a valuable quantitative assessment of the interaction between heartbeat dynamics and hemodynamics. To illustrate the application, we have applied the proposed point process model to experimental recordings from 11 healthy subjects in order to monitor cardiovascular regulation under propofol anesthesia. We present quantitative results during transient periods, as well as statistical analyses on steady-state epochs before and after propofol administration. Our findings validate the ability of the algorithm to provide a reliable and fast-tracking assessment of BRS, and show a clear overall reduction in baroreflex gain from the baseline period to the start of propofol anesthesia, confirming that instantaneous evaluation of arterial baroreflex control of HR may yield important implications in clinical practice, particularly during anesthesia and in postoperative care.

Blood pressure variability and closed-loop baroreflex assessment in adolescent chronic fatigue syndrome during supine rest and orthostatic stress

Hemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular regulation. The aim of this study was to explore blood pressure variability and closed-loop baroreflex function at rest and during mild orthostatic stress in adolescents with CFS. We included a consecutive sample of 14 adolescents 12–18 years old with CFS diagnosed according to a thorough and standardized set of investigations and 56 healthy control subjects of equal sex and age distribution. Heart rate and blood pressure were recorded continuously and non-invasively during supine rest and during lower body negative pressure (LBNP) of –20 mmHg to simulate mild orthostatic stress. Indices of blood pressure variability and baroreflex function (α-gain) were computed from monovariate and bivariate spectra in the low-frequency (LF) band (0.04–0.15 Hz) and the high–frequency (HF) band (0.15–0.50 Hz), using an autoregressive algorithm. Variability of systolic blood pressure in the HF range was lower among CFS patients as compared to controls both at rest and during LBNP. During LBNP, compared to controls, α-gain HF decreased more, and α-gain LF and the ratio of α-gain LF/α-gain HF increased more in CFS patients, all suggesting greater shift from parasympathetic to sympathetic baroreflex control. CFS in adolescents is characterized by reduced systolic blood pressure variability and a sympathetic predominance of baroreflex heart rate control during orthostatic stress. These findings may have implications for the pathophysiology of CFS in adolescents.

Increased pulse wave velocity and not reduced ejection fraction is associated with impaired baroreflex control of heart rate in congestive heart failure

It is known that baroreflex sensitivity (BRS) is impaired in cardiac patients with myocardial infarction (MI). Nevertheless, it is unknown whether factors other than a reduced ejection fraction play a role in the baroreflex impairment of these patients. Heart failure patients [congestive heart failure (CHF), n = 31, age 63 +/- 1.2 years, mean +/- SEM)], age-matched controls (n = 29) and coronary artery disease (CAD) patients without MI (n = 29) had RR interval and arterial blood pressure (BP) continuously monitored. Baroreflex function was assessed by the slope of the regression of RR interval, and BP responses to graded (-10, -20 and -40 mmHg) neck suction stimulation, the slope of bradycardic or tachycardic responses to spontaneous increases or reductions of SBP (sequence analysis) and the baroreflex efficiency index. Pulse wave velocity (PWV) was also measured.Compared with controls, CHF patients had RR interval and BP reflex responses to neck suction reduced by -36 and -54%, respectively (P < 0.01). By contrast, no differences were found between CHF and CAD patients. Similar reductions were observed for the sequence analysis (P < 0.01) in both CHF and CAD patients. Multiple regression analysis showed that in CHF and CAD patients, PWV and SBP and not ejection fraction were correlated with BRS. The baroreflex function is impaired in CHF patients, the extent and the degree of baroreflex impairment being similar to that of CAD patients without MI. In CHF and CAD patients, the baroreflex impairment correlates significantly with the increased PWV and not with ejection fraction.

Drinking and arterial blood pressure responses to ANG II in young and old rats

We investigated water drinking and arterial blood pressure responses to intravenous infusions of ANG II in young (4 mo), middle-aged adult (12 mo), and old (29 mo) male Brown Norway rats. Infusions of ANG II began with arterial blood pressure either at control levels or at reduced levels following injection of the vasodilator minoxidil. Under control conditions, mean arterial pressure (MAP) in response to ANG II rose to the same level for all groups, and middle-aged and old rats drank as much or more water in response to ANG II compared with young rats, depending on whether intakes were analyzed using absolute or body weight-adjusted values. When arterial blood pressure first was reduced with minoxidil, MAP in response to ANG II stabilized at significantly lower levels compared with control conditions for all groups. Young rats drank significantly more water under reduced pressure conditions compared with control conditions, while middle-aged and old rats did not. Urine volume in response to ANG II was lower, while water balance was higher, under conditions of reduced pressure compared with control conditions. Baroreflex control of heart rate was substantially reduced in old rats compared with young and middle-aged animals. In summary, young rats appear to be more sensitive to the inhibitory effects of increased arterial blood pressure on water drinking than are older animals.

Cardiovascular function in the heat‐stressed human

Heat stress, whether passive (i.e. exposure to elevated environmental temperatures) or via exercise, results in pronounced cardiovascular adjustments that are necessary for adequate temperature regulation as well as perfusion of the exercising muscle, heart and brain. The available data suggest that generally during passive heat stress baroreflex control of heart rate and sympathetic nerve activity are unchanged, while baroreflex control of systemic vascular resistance may be impaired perhaps due to attenuated vasoconstrictor responsiveness of the cutaneous circulation. Heat stress improves left ventricular systolic function, evidenced by increased cardiac contractility, thereby maintaining stroke volume despite large reductions in ventricular filling pressures. Heat stress-induced reductions in cerebral perfusion likely contribute to the recognized effect of this thermal condition in reducing orthostatic tolerance, although the mechanism(s) by which this occurs is not completely understood. The combination of intense whole-body exercise and environmental heat stress or dehydration-induced hyperthermia results in significant cardiovascular strain prior to exhaustion, which is characterized by reductions in cardiac output, stroke volume, arterial pressure and blood flow to the brain, skin and exercising muscle. These alterations in cardiovascular function and regulation late in heat stress/dehydration exercise might involve the interplay of both local and central reflexes, the contribution of which is presently unresolved.

Reinforcement of the adrenergic overdrive in the metabolic syndrome complicated by obstructive sleep apnea

Metabolic syndrome is characterized by a marked sympathetic overactivity. It is unknown, however, whether the neuroadrenergic activation can be ascribed to obstructive sleep apnoea (OSA), OSA exerts potentiating effects on the metabolic syndrome-related sympathetic activation and reflex/metabolic variables (insulin resistance) participate at the phenomenon. We conducted a cross-sectional study of healthy individuals and metabolic syndrome patients recruited in our outpatient clinic. Fifty-five middle-age men classified according to Adult Treatment Panel III criteria and apnea-hypopnea index (overnight polysomnographic evaluation) as healthy controls without OSA and metabolic syndrome patients without and with OSA were studied. Blood pressure (Finapres), heart rate (ECG) and muscle sympathetic nerve activity (MSNA; microneurography) were measured at rest and during baroreflex manipulation. Compared with controls, patients with metabolic syndrome with and without OSA displayed higher waist-hip ratio, blood pressure, triglycerides and homeostasis model assessment index values but lower high-density lipoprotein cholesterol. MSNA was significantly higher in patients with metabolic syndrome without OSA than in controls (61.9 +/- 3.9 vs. 37.7 +/- 4.1 bursts/100 heartbeats, respectively, P < 0.01), a further marked increase being detected in patients with metabolic syndrome with OSA (77.1 +/- 4.3 bursts/100 heart beats, P < 0.01). Compared with controls, baroreflex control of heart rate and MSNA was markedly impaired in patients with metabolic syndrome with OSA, a further impairment in baroreflex-heart rate modulation being detected in metabolic syndrome with OSA. In the metabolic syndrome group as a whole, at the multivariate analysis, MSNA was significantly related to the apnoea-hypopnoea index but not to other variables. Thus the sympathetic activation of metabolic syndrome occurs independently on OSA. OSA, however, markedly potentiates this neuroadrenergic abnormality via a hypoxic-dependent chemoreflex activation.

Independent role of reduced arterial baroreflex sensitivity during head-up tilt testing in predicting vasovagal syncope recurrence

The involvement of arterial baroreflex function in the pathophysiology of vasovagal syncope (VVS) is controversial, and there are no published data supporting its clinical usefulness. The aim of this study was to evaluate the role of arterial baroreflex sensitivity (BRS) at baseline and during head-up tilt testing (HUT) in predicting the recurrence of VVS. The study involved otherwise healthy patients with a history of unexplained syncope who underwent diagnostic HUT by being tilted to 70 degrees after 10 min supine rest; the test was potentiated by the administration of 300 microg of nitroglycerine (NTG) after 20 min. Beat-to-beat heart rate and systolic blood pressure were continuously recorded, and the sequence method was used to measure arterial baroreflex control of heart rate. The 190 enrolled patients were followed up for 18 +/- 6 months, during which 34 experienced a total of 90 episodes of syncope recurrence. In a stepwise multivariate analysis, female gender [hazard ratio (HR): 2.74; P = 0.008], the presence of >or=3 syncope events before HUT (HR: 3.36; P = 0.004), and BRS below median value after the start of HUT or after the administration of NTG (HR: 3.79; P = 0.006) were significantly and independently associated with the recurrence of syncope. Moreover, when a BRS value of less than the median was added to the other independent factors in a stepwise model, a significant increase in discrimination (C-index: 0.77) and model fitting (P = 0.001) was observed. Reduced BRS during HUT has independent and incremental value in predicting the recurrence of syncope, thus supporting its potential usefulness in the clinical management of patients.

Baroreflex control of heart rate in the broad-nosed caiman Caiman latirostris is temperature dependent

It has been suggested that ectothermic vertebrates primarily control blood pressure to protect the pulmonary vasculature from oedema caused by high pressure, while endothermic vertebrates control blood pressure to maintain adequate oxygen delivery to the tissues. In the present study we have characterised how temperature affects the cardiac limb of the baroreflex in the intact unanaesthetized broad-nosed caiman (Caiman latirostris) by pharmacological manipulation of blood pressure in a “closed-loop” system. Sodium nitroprusside (SNP) and phenylephrine were used to manipulate arterial pressure and the resulting alterations in heart rate were used to calculate the gain of the baroreflex. Both drugs were infused as bolus injections in concentrations of 5, 10, 25, 50 and 100µgkg−1. The barostatic response was present at both 15 and 30°C, and, at both temperatures, C. latirostris responded to reductions in systemic blood pressure (Psys). At 30°C the baroreflex was more pronounced at a blood pressure lower than control value (52.3cmH2O) with a maximal baroreflex gain of 1.97beatsmin−1cmH2O−1 at a Psys of 41.9cmH2O, and therefore seems to counteract hypotension. In contrast, the maximal baroreflex at 15°C was found at a Psys almost equal to the control value. The highest baroreflex gain in response to change in blood pressure was measured at the highest temperature. Thus, C. latirostris exhibit a temperature dependent barostatic response.

Maternal Diabetes Increases Small Conductance Ca2+‐activated K+ (SK) Currents Which Alters Action Potential Properties and Excitability of Cardiac Motoneurons in the Nucleus Ambiguus

Maternal diabetes (MD) impairs baroreflex control of heart rate. PCMNs play a key role in the baroreflex. We examined the effects of MD on excitability, action potential (AP) properties and SK channels of PCMNs. Neonatal mice from OVE26 diabetic (Type 1) mothers (NMDM) and normal FVB mothers (control) were used. XRITC was injected into the pericardial sac at P7–9 to label PCMNs. Two days later, XRITC‐labeled PCMNs in slices were identified. Whole‐cell (current and voltage) clamps were used to measure spike frequency, repolarization (half‐width), afterhyperpolarization (AHP), outward currents, and afterhyperpolarization currents (IAHP). Compared to control, we found (p&lt;0.05) in NMDM that: 1) spike frequency decreased; 2) the half‐width and AHP peak amplitude increased; 3) the peak amplitude of outward transient currents and IAHP increased; 4) Cd2+ (Ca2+ channels blocker)‐sensitive transient outward currents and IAHP increased; 5) application of Cd2+ increased AP half‐width and decreased AHP amplitude; 6) apamin‐sensitive transient outward currents and IAHP increased; 7) blockade of SK channels with apamin increased AP half‐width and decreased AHP amplitude; 8) apamin application increased the firing rate to current injections and largely abolished the difference of the firing rate between control and NMDM. We suggest that the augmented SK currents may contribute to altered AP properties and the attenuated excitability of PCMNs in NMDM. NIH R01 HL79636.

Comparison of the pharmacological and sequence methods for assessing baroreflex control blood pressure via heart rate and renal sympathetic nerve activity

In many cardiovascular diseases, the sensitivity of the baroreflex is impaired. To determine baroreflex sensitivity in the laboratory, we have traditionally infused vasoactive drugs to alter blood pressure and recorded the responses of renal sympathetic nerve activity and heart rate. However, the pharmacological method is not always practical and thus there is a shift to obtaining baroreflex response curves from naturally occurring fluctuations in arterial pressure. The aim of this project was to establish the practicalities of using spontaneous fluctuations in arterial pressure to determine the sensitivity of the baroreflex in conscious unrestrained animals and make comparisons to traditional pharmacological methods. Gains of the baroreflex control of heart rate were comparable between the two methods but spontaneous baroreflex gains for the baroreflex control for sympathetic nerve activity were greater than those obtained from pharmacological methods. It must also be noted that the sequence methods only provides gain measurements and no information on the operating range of the reflex. Supported by the Health Research Council of New Zealand and University of Auckland Research Committee.

The hypothalamic paraventricular nucleus is required for insulin's action to increase baroreflex gain of lumbar sympathetic nerve activity

During pregnancy, low brain insulin levels are associated with impaired baroreflex control of heart rate (HR) and sympathetic nerve activity (SNA), and intracerebral insulin infusion normalizes baroreflex gain (BRG). The specific site of insulin action is unknown, though a likely candidate is the paraventricular nucleus (PVN). To test this hypothesis, BRG of lumbar SNA (LSNA) and HR were obtained in chloralose anesthetized female rats before and at 30min intervals during iv infusion of insulin (15mU/kg/min, n=5) or saline (n=5). Insulin increased LSNA (P&lt;0.05; in % baseline) to 166±18 (30min), 224±43 (60min), 219±46 (90min), and 227±49 (120min). Similarly, insulin increased LSNA BRG (P&lt;0.05; in %LSNA/mmHg) from 2.6±0.8 to 2.9±0.7 (30min), 4.5±0.9 (60min), 4.3±0.5 (90min), and 4.7±0.6 (120min). Insulin did not affect basal HR or HR BRG. No changes in LSNA, HR or BRG were observed with saline infusion. In another group (n=4), the effect of insulin to increase LSNA and LSNA gain was reversed by blockade of PVN via bilateral microinjection of muscimol (M; 60nL of 1mM). LSNA (% baseline) increased to 223±37 after insulin and fell to 126±11 after M (P&lt;0.05). LSNA gain (%LSNA/mmHg) increased from 2.8±1.3 to 4.4±1.2, and decreased to 2.4±0.7 after M (P&lt;0.05). In summary, iv insulin increased LSNA and LSNA gain. This action was reversed by PVN blockade, suggesting that insulin acts via the PVN to improve BRG. Support: the EMBL/GenBank Data Libraries under Accession No. HL088552

Diet‐induced obesity differentially affects baroreflex‐mediated sympathetic and parasympathetic outflow

Diet‐induced obesity (DIO) impairs the baroreflex control of heart rate (HR), which may arise from differential influences of the sympathetic (SNS) and parasympathetic (PNS) nervous systems. To test this hypothesis, Δ mean arterial pressure (MAP) and Δ HR to 30‐sec maximal stimulation of the aortic baroreceptors (aortic depressor nerve; 20V, 100Hz) were recorded before and after muscarinic receptor blockade (MB; methscopolamine, iv bolus 500ug/kg) in inactin‐anesthetized male SD rats. Rats were fed a normal (N, 13.5% kcal fat) or high fat diet (HFD, 33% kcal fat) for 4–5 weeks. Rats fed the HFD were separated into obesity prone (OP) or resistant (OR) groups, based on the top and bottom tertile of weight gain, respectively. Baseline values did not differ between groups.As shown in the table above, Δ HR and Δ MAP were blunted in OP rats compared to N and OR rats (†p&lt;0.05 vs OP). Removal of PNS influence with MB attenuated Δ HR and Δ MAP in N and OR rats (*p&lt;0.05 control vs MB), which were similar to the OP rat control responses. MB had no effect on the OP group. These findings suggest that DIO impairs aortic baroreceptor activation of the PNS, but may minimally impact the SNS. Funded by AHA (Brooks) and NIH (McCully NS045553, Brooks HL088552, Andresen HL41119). Δ HR (bpm) Δ MAP (mmHg) Control MB Control MB N (n=6) −53±7† −28±4* −57±6† −47±4* OR (n=6) −45±6† −31±3* −60±5† −48±4* OP (n=6) −30±6 −28±6 −41±8 −47±4

Alterations in carotid baroreflex control of arterial blood pressure during the menstrual cycle in young women

Limited studies have suggested that menstrual cycle variations in sex hormones may influence arterial baroreflex control of heart rate (HR) and sympathetic nerve activity; however, results are equivocal. In addition, the baroreflex control of blood pressure (BP) has not been directly examined as pharmacological perturbations were mainly used to assess baroreflex function. Therefore, 5s pulses of neck suction (NS, −60 Torr) and neck pressure (NP, +40 Torr) were applied to load and unload the carotid baroreflex (CBR), respectively in young women during the early follicular (EF, day 1–5, low estrogen, low progesterone), late follicular (LF, day 10–12, high estrogen, low progesterone), and mid luteal (ML, day 20–24, high estrogen, high progesterone) menstrual cycle phases. Resting HR and BP were not different between the 3 phases. Similarly, HR responses to NP and NS were not significantly different between phases. In contrast, mean BP responses to NP were significantly greater in the ML phase (Δ17±1 vs. Δ13±1 EF; Δ13±2 LF mmHg; P&lt;0.05); however, responses to NS were not significantly different between phases (EF Δ−10±2, LF Δ−10±1, and ML Δ−10±1 mmHg). These preliminary findings suggest a maintained CBR control of HR throughout the menstrual cycle whereas concomitant elevations in estrogen and progesterone selectively augment CBR‐mediated BP responses to hypotension without effect on CBR responses to hypertension.Supported by R01HL093167.

Central Ang‐(1–7) enhances baroreflex gain in rabbits with chronic heart failure

In chronic heart failure (CHF), arterial baroreflex function is impaired in part by activation of the central renin‐angiotensin system. A metabolite of Angiotensin II (Ang II), Ang‐(1–7), has been shown to exhibit cardiovascular effects that are in opposition to that of Ang II. However, the action of Ang‐(1–7) on sympathetic outflow and baroreflex function is not well understood, especially in CHF. This study aimed to determine the effect of intracerebroventricular infusion of Ang‐(1–7) on baroreflex control of heart rate (HR) in rabbits with CHF. We hypothesized that central Ang‐(1–7) would improve baroreflex function in CHF. Ang‐(1–7) (2 nmol/μl/hour) or artificial cerebrospinal fluid (1 μl/hour) was infused by an osmotic mini‐pump for 4 days in sham and pacing‐induced CHF rabbits (n=5–6/group). CHF rabbits showed depressed baroreflex gain in the conscious state. Ang‐(1–7) treatment increased baroreflex gain (7.4±1.5 bpm/mm Hg vs. 2.5±0.4 bpm/mm Hg, P&lt;.05). Central Ang‐(1–7) improved baroreflex control in CHF by lowering minimum HR and increasing maximum gain. This suggests that modulation of baroreflex function by Ang‐(1–7) may be due to increased vagal tone.Source of support: PO1 HL‐62222

Changes in autonomic control of the cardiovascular system in the Wistar audiogenic rat (WAR) strain, an experimental model of epilepsy

This study aimed to evaluate autonomic cardiovascular modulation and baroreflex control of heart rate (HR) in Wistar audiogenic rats (WAR), an epileptic rat strain. We studied spontaneous baroreflex (sequence method) as well as reflex changes in HR evoked by phenylephrine or nitroprusside‐induced changes in arterial pressure (AP). Blockers of autonomic receptors (atropine and propranolol) were used to measure cardiac autonomic tone. Pulse interval (PI) and AP variability analyses were performed by FFT spectral analysis to evaluate cardiovascular sympathovagal modulation. In WAR, AP and HR were higher (109±2 mmHg and 366±9 bpm) as compared with Wistar rats (101±2 mmHg and 326±10 bpm). Power in the low frequency (0.2–0.8 Hz) band, a marker of sympathetic activity, was higher in the AP and PI spectra of WAR than in those of Wistar rats. High frequency (0.8–3 Hz) power of PI spectra, which is linked to cardiac vagal modulation, was lower in WAR. Both strains showed similar vagal tone (91±13 vs. 94±11 bpm) but sympathetic tone was higher in WAR (30±4 vs. 14±4 bpm). No differences were found in the gains of evoked (1.32±0.1 vs. 1.35±0.2 ms/mmHg) or spontaneous (1.34±0.2 vs. 2.04±0.2 ms/mmHg) baroreflex sensitivity. Higher AP and HR are well known to be associated with sympathetic predominance and with threatening cardiovascular events, which are typical causes of sudden unexpected death in epilepsy. Support: FAPESP, CNPq.

Identifying physiological origins of baroreflex dysfunction in salt-sensitive hypertension in the Dahl SS rat

Salt-sensitive hypertension is known to be associated with dysfunction of the baroreflex control system in the Dahl salt-sensitive (SS) rat. However, neither the physiological mechanisms nor the genomic regions underlying the baroreflex dysfunction seen in this rat model are definitively known. Here, we have adopted a mathematical modeling approach to investigate the physiological and genetic origins of baroreflex dysfunction in the Dahl SS rat. We have developed a computational model of the overall baroreflex heart rate control system based on known physiological mechanisms to analyze telemetry-based blood pressure and heart rate data from two genetic strains of rat, the SS and consomic SS.13(BN), on low- and high-salt diets. With this approach, physiological parameters are estimated, unmeasured physiological variables related to the baroreflex control system are predicted, and differences in these quantities between the two strains of rat on low- and high-salt diets are detected. Specific findings include: a significant selective impairment in sympathetic gain with high-salt diet in SS rats and a protection from this impairment in SS.13(BN) rats, elevated sympathetic and parasympathetic offsets with high-salt diet in both strains, and an elevated sympathetic tone with high-salt diet in SS but not SS.13(BN) rats. In conclusion, we have associated several important physiological parameters of the baroreflex control system with chromosome 13 and have begun to identify possible physiological mechanisms underlying baroreflex impairment and hypertension in the Dahl SS rat that may be further explored in future experimental and modeling-based investigation.

Chronic Antioxidant Treatment Improves Arterial Renovascular Hypertension and Oxidative Stress Markers in the Kidney in Wistar Rats

Sympathetic vasomotor hyperactivity and baroreflex dysfunction are involved in the development and maintenance of renovascular arterial hypertension. We hypothesized that angiotensin (Ang) II-dependent oxidative stress contributes to the pathophysiology of the two-kidney, one-clip (2K-1C) model. The mean arterial pressure (MAP), baroreflex, and renal sympathetic nerve activity (rSNA) were evaluated after chronic administration of an antioxidant, vitamin C (vitC 150 mg/kg/day) in male Wistar 2K-1C rats. Additionally, the mRNA levels of Ang II subtype 1 receptor (AT(1)R), NAD(P)H oxidase subunits (p47phox and gp91phox), and major antioxidant enzymes were evaluated in the renal cortex. After vitC treatment, the MAP (170 +/- 4 vs. 133 +/- 6 mm Hg; P < 0.05) and rSNA (161 +/- 5 vs. 118 +/- 12 spikes/s; P < 0.05) were significantly reduced only in the 2K-1C group. VitC improved the baroreflex control of heart rate (HR) and rSNA. The expression of AT(1)R, p47phox, and gp91phox was elevated (51, 184, and 132%, respectively) in the clipped kidney of 2K-1C group. VitC downregulated AT(1)R in the clipped kidney (31%). Catalase (CAT) expression was reduced in clipped (70%) and nonclipped (83%) kidneys of 2K-1C rats. VitC treatment augmented the expression of glutathione peroxidase (GPx) in both clipped (185%) and nonclipped (212%) kidneys of the 2K-1C group. The present study suggests a role for oxidative stress in the cardiovascular and sympathetic alterations in renovascular hypertension, associated with changes in the expression of AT(1)R, NAD(P)H oxidase subunits, and antioxidant enzymes in the kidney.

Impairment of baroreflex control of heart rate and structural changes of cardiac ganglia in conscious streptozotocin (STZ)-induced diabetic mice

Baroreflex control of heart rate (HR) is impaired in human diabetes mellitus and in large experimental models. However, baroreflex impairment in diabetic mouse models and diabetes-induced remodeling of baroreflex circuitry are not well studied. We examined the impairment of baroreflex control of heart rate (HR) and assessed structural remodeling of cardiac ganglia in the streptozotocin (STZ)-induced diabetic mouse model. FVB mice were either injected with vehicle or STZ. Group 1: mice were anesthetized and the femoral artery and vein were catheterized at the 30th day after vehicle or STZ injection. On the second day after surgery, baroreflex-mediated HR responses to sodium nitroprusside (SNP) and phenylephrine (PE)-induced mean arterial blood pressure (MABP) changes were measured in conscious mice. Group 2: Fluoro-Gold was administered (i.p.) to label cardiac ganglia in each mouse at the 25th day after vehicle or STZ injection. After another five days, animals were perfused and cardiac ganglia were examined using confocal microscopy. Compared with control, we found in STZ mice: 1) the HR decreased, but MABP did not. 2) The PE-induced increases of MABP were decreased. 3) Baroreflex bradycardia was attenuated in the rapid MABP ascending phase but the steady-state ΔHR/ΔMABP was not different at all PE doses. 4) SNP-induced MABP decreases were not different. 5) Baroreflex tachycardia was attenuated. 6) The sizes of cardiac ganglia and ganglionic principal neurons were decreased. 7) The ratio of nucleus/cell body of cardiac ganglionic neurons was increased. We conclude that baroreflex control of HR is impaired in conscious STZ mice. In addition, diabetes may induce a significant structural remodeling of cardiac ganglia. Such an anatomical change of cardiac ganglia may provide new information for the understanding of diabetes-induced remodeling of the multiple components within the baroreflex circuitry.

High sugar intake via the renin-angiotensin system blunts the baroreceptor reflex in adult rats that were perinatally depleted of taurine

Perinatal taurine depletion leads to several physiological impairments in adult life, in part, due to taurine’s effects on the renin-angiotensin system, a crucial regulator of growth and differentiation during early life. The present study tests the hypothesis that perinatal taurine depletion predisposes adult female rats to impaired baroreceptor control of arterial pressure by altering the renin-angiotensin system. Female Sprague Dawley (SD) rats were fed normal rat chow and from conception to weaning drank 3% beta-alanine in water (taurine depletion, TD) or water alone (Control, C). Female offspring ate a normal rat chow and drank water with (G) or without (W) 5% glucose throughout the experiment. To test the possible role of the renin-angiotensin system, 50% of the rats received captopril (an angiotensin converting enzyme inhibitor, 400 mg/L) from 7 days before parameter measurements until the end of experiment. At 7-8 weeks of age, arterial pressure, heart rate, baroreflex control of heart rate and renal nerve activity were studied in either conscious, freely moving or anesthetized rats. Perinatal taurine depletion did not alter resting mean arterial pressure or heart rate in the adult female offspring that received either high or normal sugar intake. Captopril treatment slightly decreased mean arterial pressure but not heart rate in all groups. Compared to controls, only the TDG rats displayed blunted baroreflex responses. Captopril treatment normalized baroreflex sensitivity in TDG. The present data indicate that in perinatal taurine depleted female rats, the renin-angiotensin system underlines the ability of high sugar intake to blunt baroreceptor responses.

Progressive muscle metaboreflex activation gradually decreases spontaneous heart rate baroreflex sensitivity during dynamic exercise

Ischemia of active skeletal muscle elicits a pressor response termed the muscle metaboreflex. We tested the hypothesis that in normal dogs during dynamic exercise, graded muscle metaboreflex activation (MMA) would progressively attenuate spontaneous heart rate baroreflex sensitivity (SBRS). The animals were chronically instrumented to measure heart rate (HR), cardiac output (CO), mean and systolic arterial pressure (MAP and SAP), and left ventricular systolic pressures (LVSP) at rest and during mild or moderate treadmill exercise before and during progressive MMA [via graded reductions of hindlimb blood flow (HLBF)]. SBRS [slopes of the linear relationships (LRs) between HR and LVSP or SAP during spontaneous sequences of > or =3 consecutive beats when HR changed inversely vs. pressure] decreased during mild exercise from the resting values (-5.56 +/- 0.86 vs. -2.67 +/- 0.50 beats.min(-1).mmHg(-1), P <0.05), and in addition, these LRs were shifted upward. Progressive MMA gradually and linearly increased MAP, CO, and HR; linearly decreased SBRS; and shifted LRs upward and rightward to higher HR and pressures denoting baroreflex resetting. Moderate exercise caused a substantial reduction in SBRS (-1.57 +/- 0.38 beats.min(-1).mmHg(-1), P <0.05) and both an upward and rightward resetting. Gradual MMA at this higher workload also caused significant progressive increases in MAP, CO, and HR and progressive decreases in SBRS, and the LRs were shifted to higher MAP and HR. Our results demonstrate that gradual MMA during mild and moderate dynamic exercise progressively decreases SBRS. In addition, baroreflex control of HR is progressively reset to higher blood pressure and HR in proportion to the extent of MMA.