Enhanced open-loop but not closed-loop cardiac baroreflex sensitivity during orthostatic stress in humans

The neural interaction between the cardiopulmonary and arterial baroreflex may be critical for the regulation of blood pressure during orthostatic stress. However, studies have reported conflicting results: some indicate increases and others decreases in cardiac baroreflex sensitivity (i.e., gain) with cardiopulmonary unloading. Thus the effect of orthostatic stress-induced central hypovolemia on regulation of heart rate via the arterial baroreflex remains unclear. We sought to comprehensively assess baroreflex function during orthostatic stress by identifying and comparing open- and closed-loop dynamic cardiac baroreflex gains at supine rest and during 60° head-up tilt (HUT) in 10 healthy men. Closed-loop dynamic "spontaneous" cardiac baroreflex sensitivities were calculated by the sequence technique and transfer function and compared with two open-loop carotid-cardiac baroreflex measures using the neck chamber system: 1) a binary white-noise method and 2) a rapid-pulse neck pressure-neck suction technique. The gain from the sequence technique was decreased from -1.19 ± 0.14 beats·min(-1)·mmHg(-1) at rest to -0.78 ± 0.10 beats·min(-1)·mmHg(-1) during HUT (P = 0.005). Similarly, closed-loop low-frequency baroreflex transfer function gain was reduced during HUT (P = 0.033). In contrast, open-loop low-frequency transfer function gain between estimated carotid sinus pressure and heart rate during white-noise stimulation was augmented during HUT (P = 0.01). This result was consistent with the maximal gain of the carotid-cardiac baroreflex stimulus-response curve (from 0.47 ± 0.15 beats·min(-1)·mmHg(-1) at rest to 0.60 ± 0.20 beats·min(-1)·mmHg(-1) at HUT, P = 0.037). These findings suggest that open-loop cardiac baroreflex gain was enhanced during HUT. Moreover, under closed-loop conditions, spontaneous baroreflex analyses without external stimulation may not represent open-loop cardiac baroreflex characteristics during orthostatic stress.     

Attenuation of sympathetic baroreflex sensitivity during the onset of acute mental stress in humans

Mental stress consistently induces a pressor response that is often accompanied by a paradoxical increase of muscle sympathetic nerve activity (MSNA). The purpose of the present study was to evaluate sympathetic baroreflex sensitivity (BRS) by examining the relations between spontaneous fluctuations of diastolic arterial pressure (DAP) and MSNA. We hypothesized that sympathetic BRS would be attenuated during mental stress. DAP and MSNA were recorded during 5 min of supine baseline, 5 min of mental stress, and 5 min of recovery in 32 young healthy adults. Burst incidence and area were determined for each cardiac cycle and placed into 3-mmHg DAP bins; the slopes between DAP and MSNA provided an index of sympathetic BRS. Correlations between DAP and MSNA were strong (> 0.5) during baseline in 31 of 32 subjects, but we evaluated the change in slope only for those subjects maintaining a strong correlation during mental stress (16 subjects). During baseline, the relation between DAP and MSNA was negative when expressed as either burst incidence [slope = -1.95 ± 0.18 bursts·(100 beats)?1)·mmHg?1; r = -0.86 ± 0.03] or total MSNA [slope = -438 ± 91 units·(beat)?1 mmHg?1; r = -0.76 ± 0.06]. During mental stress, the slope between burst incidence and DAP was significantly reduced [slope = -1.14 ± 0.12 bursts·(100 beats)?1·mmHg?1; r = -0.72 ± 0.03; P < 0.01], indicating attenuation of sympathetic BRS. A more detailed analysis revealed an attenuation of sympathetic BRS during the first 2 min of mental stress (P < 0.01) but no change during the final 3 min of mental stress (P = 0.25). The present study demonstrates that acute mental stress attenuates sympathetic BRS, which may partially contribute to sympathoexcitation during the mental stress-pressor response. However, this attenuation appears to be isolated to the onset of mental stress. Moreover, variable MSNA responses to mental stress do not appear to be directly related to sympathetic BRS.     

Time domain baroreflex sensitivity assessment by joint analysis of spontaneous SBP and RR series

The sequences technique is frequently used for time domain assessment of the arterial-cardiac baroreceptor reflex sensitivity (BRS). The BRS is estimated by the slope between systolic blood pressure and RR interval values in baroreflex sequences (BSs) and an overall estimate is obtained by slope averaging. However, only 25% of all beats are in BSs with 60% of those located in 3-beat length segments. Also, in cases of BSs absence (usually associated with poor BRS function), the BRS cannot be quantified.Here, baroreflex events (BEs) are introduced and used with global/total slope estimators to improve BRS assessment. The performance of the novel method is evaluated using the EuroBaVar dataset. The events technique benefits from a higher number of beats: 50% of all beats are in BEs with more than 70% exceeding 3-beat length. It always provides a BRS estimate, even when BSs cannot be identified. When BSs are available, estimates from BEs and BSs are highly correlated. The estimates from BEs for the cases without BSs are lower than the estimates for the remaining cases, indicating poorer BRS function. The events technique also offers superior ability to discriminate lying from standing position in the EuroBaVar dataset (23/23 versus 18/23 for the sequences technique).     

Carotid distensibility, baroreflex sensitivity, and orthostatic stress.

In this study, we tested the hypothesis that carotid arteries undergo rapid changes in distensibility on moving from the supine to head-up tilt (HUT) postures and, subsequently, that this change in carotid distensibility (cDa) might be associated with concurrent reductions in cardiovagal baroreflex sensitivity (BRS). Thus the effect of posture on carotid vascular mechanics and cardiovagal BRS with consideration for altered central hemodynamics (i.e., stroke volume; Doppler ultrasound) was examined. Carotid pulse pressure (cPP; Millar transducer) and contralateral B-mode ultrasound images were assessed at the carotid artery during supine and 60 degrees HUT postures. From these measures, cDa was calculated at 5-mmHg pressure increments experienced during the cardiac cycle (n = 6). cPP (n = 9) was not different in the two postures. A smaller stroke volume being ejected into a smaller carotid artery in HUT explained the maintenance of cPP in HUT. Also, compared with supine, cDa was reset to a lower level in HUT (main effect of posture; P < 0.05). Cardiovagal BRS (sequence method) was diminished in HUT vs. supine (P < 0.05). A positive correlation was observed between the tilt-induced changes in maximal cDa (in early systole) and cardiovagal BRS (r2 = 0.75; P < 0.05), but there was little predictive relationship between changes in cPP, systolic vessel dimensions, or average cDa and the corresponding change in BRS. The present results indicate that HUT elicits rapid changes in carotid artery mechanics and further suggest that reductions in the maximal cDa measured in early systole contribute to reduced cardiovagal BRS with HUT.     

Interaction between vestibulo-cardiovascular reflex and arterial baroreflex during postural change in rats

To examine a cooperative role for the baroreflex and the vestibular system in controlling arterial pressure (AP) during voluntary postural change, AP was measured in freely moving conscious rats, with or without sinoaortic baroreceptor denervation (SAD) and/or peripheral vestibular lesion (VL). Voluntary rear-up induced a slight decrease in AP (-5.6 ± 0.8 mmHg), which was significantly augmented by SAD (-14.7 ± 1.0 mmHg) and further augmented by a combination of VL and SAD (-21 ± 1.0 mmHg). Thus we hypothesized that the vestibular system sensitizes the baroreflex during postural change. To test this hypothesis, open-loop baroreflex analysis was conducted on anesthetized sham-treated and VL rats. The isolated carotid sinus pressure was increased stepwise from 60 to 180 mmHg while rats were placed horizontal prone or in a 60° head-up tilt (HUT) position. HUT shifted the carotid sinus pressure-sympathetic nerve activity (SNA) relationship (neural arc) to a higher SNA, shifted the SNA-AP relationship (peripheral arc) to a lower AP, and, consequently, moved the operating point to a higher SNA while maintaining AP (from 113 ± 5 to 114 ± 5 mmHg). The HUT-induced neural arc shift was completely abolished in VL rats, whereas the peripheral arc shifted to a lower AP and the operating point moved to a lower AP (from 116 ± 3 to 84 ± 5 mmHg). These results indicate that the vestibular system elicits sympathoexcitation, shifting the baroreflex neural arc to a higher SNA and maintaining AP during HUT.     

Determination of baroreflex sensitivity during the modified Oxford maneuver by trigonometric regressive spectral analysis

Background

Differences in spontaneous and drug-induced baroreflex sensitivity (BRS) have been attributed to its different operating ranges. The current study attempted to compare BRS estimates during cardiovascular steady-state and pharmacologically stimulation using an innovative algorithm for dynamic determination of baroreflex gain.

Methodology/Principal Findings

Forty-five volunteers underwent the modified Oxford maneuver in supine and 60° tilted position with blood pressure and heart rate being continuously recorded. Drug-induced BRS-estimates were calculated from data obtained by bolus injections of nitroprusside and phenylephrine. Spontaneous indices were derived from data obtained during rest (stationary) and under pharmacological stimulation (non-stationary) using the algorithm of trigonometric regressive spectral analysis (TRS). Spontaneous and drug-induced BRS values were significantly correlated and display directionally similar changes under different situations. Using the Bland-Altman method, systematic differences between spontaneous and drug-induced estimates were found and revealed that the discrepancy can be as large as the gain itself. Fixed bias was not evident with ordinary least products regression. The correlation and agreement between the estimates increased significantly when BRS was calculated by TRS in non-stationary mode during the drug injection period. TRS-BRS significantly increased during phenylephrine and decreased under nitroprusside.

Conclusions/Significance

The TRS analysis provides a reliable, non-invasive assessment of human BRS not only under static steady state conditions, but also during pharmacological perturbation of the cardiovascular system.     

Arterial baroreflex control of heart rate during exercise in postural tachycardia syndrome.

Patients with postural tachycardia syndrome (POTS) have excessive tachycardia without hypotension during orthostasis as well as exercise. We tested the hypothesis that excessive tachycardia during exercise in POTS is not related to abnormal baroreflex control of heart rate (HR). Patients (n = 13) and healthy controls (n = 10) performed graded cycle exercise at 25, 50, and 75 W in both supine and upright positions while arterial pressure (arterial catheter) and HR (ECG) were measured. Baroreflex sensitivity of HR was assessed by bolus intravenous infusion of phenylephrine at each workload. In both positions, HR was higher in the patients than the controls during exercise. Supine baroreflex sensitivity (HR/systolic pressure) in POTS patients was -1.3 +/- 0.1 beats.min(-1).mmHg(-1) at rest and decreased to -0.6 +/- 0.1 beats.min(-1).mmHg(-1) during 75-W exercise, neither significantly different from the controls (P > 0.6). In the upright position, baroreflex sensitivity in POTS patients at rest (-1.4 +/- 0.1 beats.min(-1).mmHg(-1)) was higher than the controls (-1.0 +/- 0.1 beats.min(-1).mmHg(-1)) (P < 0.05), and it decreased to -0.1 +/- 0.04 beats.min(-1).mmHg(-1) during 75-W exercise, lower than the controls (-0.3 +/- 0.09 beats.min(-1).mmHg(-1)) (P < 0.05). The reduced arterial baroreflex sensitivity of HR during upright exercise was accompanied by greater fluctuations in systolic and pulse pressure in the patients than in the controls with 56 and 90% higher coefficient of variations, respectively (P < 0.01). However, when baroreflex control of HR was corrected for differences in HR, it was similar between the patients and controls during upright exercise. These results suggest that the tachycardia during exercise in POTS was not due to abnormal baroreflex control of HR.     

Modeling baroreflex regulation of heart rate during orthostatic stress

During orthostatic stress, arterial and cardiopulmonary baroreflexes play a key role in maintaining arterial pressure by regulating heart rate. This study presents a mathematical model that can predict the dynamics of heart rate regulation in response to postural change from sitting to standing. The model uses blood pressure measured in the finger as an input to model heart rate dynamics in response to changes in baroreceptor nerve firing rate, sympathetic and parasympathetic responses, vestibulo-sympathetic reflex, and concentrations of norepinephrine and acetylcholine. We formulate an inverse least squares problem for parameter estimation and successfully demonstrate that our mathematical model can accurately predict heart rate dynamics observed in data obtained from healthy young, healthy elderly, and hypertensive elderly subjects. One of our key findings indicates that, to successfully validate our model against clinical data, it is necessary to include the vestibulo-sympathetic reflex. Furthermore, our model reveals that the transfer between the nerve firing and blood pressure is nonlinear and follows a hysteresis curve. In healthy young people, the hysteresis loop is wide, whereas, in healthy and hypertensive elderly people, the hysteresis loop shifts to higher blood pressure values, and its area is diminished. Finally, for hypertensive elderly people, the hysteresis loop is generally not closed, indicating that, during postural change from sitting to standing, baroreflex modulation does not return to steady state during the first minute of standing.     

Clinical value of baroreflex sensitivity

The arterial baroreflex is an important determinant of the neural regulation of the cardiovascular system. It has been recognised that baroreflex-mediated sympathoexcitation contributes to the development and progression of many cardiovascular disorders. Accordingly, the quantitative estimation of the arterial baroreceptor-heart rate reflex (baroreflex sensitivity, BRS), has been regarded as a synthetic index of neural regulation at the sinus atrial node. The evaluation of BRS has been shown to provide clinical and prognostic information in a variety of cardiovascular diseases, including myocardial infarction and heart failure that are reviewed in the present article.     

Resonance in a mathematical model of baroreflex control: arterial blood pressure waves accompanying postural stress

A mathematical model of the arterial baroreflex was developed and used to assess the stability of the reflex and its potential role in producing the low-frequency arterial blood pressure oscillations called Mayer waves that are commonly seen in humans and animals in response to decreased central blood volume. The model consists of an arrangement of discrete-time filters derived from published physiological studies, which is reduced to a numerical expression for the baroreflex open-loop frequency response. Model stability was assessed for two states: normal and decreased central blood volume. The state of decreased central blood volume was simulated by decreasing baroreflex parasympathetic heart rate gain and by increasing baroreflex sympathetic vaso/venomotor gains as occurs with the unloading of cardiopulmonary baroreceptors. For the normal state, the feedback system was stable by the Nyquist criterion (gain margin = 0.6), but in the hypovolemic state, the gain margin was small (0.07), and the closed-loop frequency response exhibited a sharp peak (gain of 11) at 0.07 Hz, the same frequency as that observed for arterial pressure fluctuations in a group of healthy standing subjects. These findings support the theory that stresses affecting central blood volume, including upright posture, can reduce the stability of the normally stable arterial baroreflex feedback, leading to resonance and low-frequency blood pressure waves.     

Nitric oxide impairs baroreflex gain during acute psychological stress

Psychological stress can suppress baroreflex function, but the mechanism has not been fully elucidated. Nitric oxide in the brain and in the adrenal cortex, as well as plasma glucocorticoids, increases during stress and has been shown to suppress reflex gain in unstressed animals. Therefore, the purpose of this study was to test the hypothesis that stress, caused by exposure to a novel environment, decreases baroreflex gain in rabbits through the actions of nitric oxide to increase corticosterone release. Baroreflex control of heart rate and plasma corticosterone levels was quantified before and after blockade of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine (L-NNA; 20 mg/kg iv) in conscious rabbits exposed to a novel environment and in the same rabbits once they had been conditioned to the environment. Stress significantly reduced baroreflex gain from -23.4 +/- 2 to -12.2 +/- 1.6 beats x min(-1) x mmHg(-1) (P < 0.05) and increased plasma corticosterone levels from 5.4 +/- 0.7 to 15.5 +/- 5.0 ng/ml (P < 0.05). NOS blockade increased gain in stressed animals (to -27.2 +/- 5.4 beats x min(-1) x mmHg(-1), P < 0.05) but did not alter gain in unstressed rabbits (-26.8 +/- 4.9 beats x min(-1) x mmHg(-1)) such that gain was equalized between the two states. NOS blockade increased plasma corticosterone levels in unstressed animals (to 14.3 +/- 2.1 ng/ml, P < 0.05) but failed to significantly alter levels in stressed rabbits (14.0 +/- 3.9 ng/ml). In conclusion, psychological stress may act via nitric oxide, independently of increases in corticosterone, to decrease baroreflex gain.     

Muscle metaboreflex attenuates spontaneous heart rate baroreflex sensitivity during dynamic exercise

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Dynamic exercise attenuates spontaneous baroreflex sensitivity (SBRS) in the control of heart rate (HR) during rapid, spontaneous changes in blood pressure (BP). Our objective was to determine whether muscle metaboreflex activation (MRA) further diminishes SBRS. Conscious dogs were chronically instrumented for measurement of HR, cardiac output, mean arterial pressure, and left ventricular systolic pressure (LVSP) at rest and during mild (3.2 km/h) or moderate (6.4 km/h at 10% grade) dynamic exercise before and after MRA (via partial reduction of hindlimb blood flow). SBRS was evaluated as the slopes of the linear relations (LRs) between HR and LVSP during spontaneous sequences of at least three consecutive beats when HR changed inversely vs. pressure (expressed as beats x min(-1) x mmHg(-1)). During mild exercise, these LRs shifted upward, with a significant decrease in SBRS (-3.0 +/- 0.4 vs. -5.2 +/- 0.4, P<0.05 vs. rest). MRA shifted LRs upward and rightward and decreased SBRS (-2.1 +/- 0.1, P<0.05 vs. mild exercise). Moderate exercise shifted LRs upward and rightward and significantly decreased SBRS (-1.2 +/- 0.1, P<0.05 vs. rest). MRA elicited further upward and rightward shifts of the LRs and reductions in SBRS (-0.9 +/- 0.1, P<0.05 vs. moderate exercise). We conclude that dynamic exercise resets the arterial baroreflex to higher BP and HR as exercise intensity increases. In addition, increases in exercise intensity, as well as MRA, attenuate SBRS.     

Gender affects sympathetic neurovascular control during postural stress

Sympathetic outflow increases during head-up tilt (HUT) to stabilize blood pressure in the presence of decreases in venous return and stroke volume (SV). Otherwise, orthostatic hypotension would develop. Gender differences in orthostatic tolerance have been noted but the mechanisms are still uncertain. More recently, Waters et al. reported in a limited sample, greater susceptibility of women to demonstrate orthostatic intolerance following space flight. Therefore, it is important to understand gender differences in reflex blood pressure regulation. Recently, we reported smaller increments in muscle sympathetic nerve activity (MSNA) in healthy women during graded HUT and a non-baroreflex cold pressor test. The purpose of this report is to examine the hypothesis that gender differences in blood pressure control during HUT are related to important variations in MSNA discharge patterns.     

Time course and variability of tendinous vibration-induced postural reactions in forward and backward directions

Mechanical vibration of tendons induces large postural reactions (PR-VIB) but little is known about how these reactions vary within and between subjects. We investigated the intra- and inter-individual variability of PR-VIB and determined the reliability of center of pressure (COP) measures. Bipodal postural control (eyes closed) of 30 healthy adults were evaluated using a force platform under 02 conditions: bilateral VIB of the tibialis anterior (TA) and Achilles tendons (ACH-T) at 80 Hz. Each condition consisted of 03 trials of 30 s duration (Baseline: 10 s; VIB: 10 s; POST-VIB: 10 s). The Amplitude and Velocity of the COP in the antero-posterior/medio-lateral (AP/ML) directions were recorded and analyzed according to 5 time-windows incremented every 2 s of vibration (i.e. the first 2 s; 4 s; 6 s; 8 s & 10 s), whereas the COP position/AP was monitored every 0.5 s. All postural parameters increased significantly during TA and ACH-T vibration compared to the Baseline. The reliability of the COP measures showed good ICC scores (0.40-0.84) and measurement errors that varied depending on the duration of VIB time-windows. The COP position/AP reveals a lower intra- and inter-subject variability of PR-VIB in the first 2 s of VIB. The metrological characteristics of PR-VIB should be investigated further to guide their future use by clinicians and researchers.     

Noninvasive determination of baroreflex sensitivity in man by means of spectral analysis.

The spectral analysis technique was applied for noninvasive assessment of heart-rate baroreflex sensitivity (BRS). The coherence between fluctuation of blood pressure and heart rate at 0.1 Hz and at respiratory frequency is high. This fact enables the assessment of BRS by means of calculating the modulus (or gain) of the transfer function between variations in blood pressure and heart rate. The noninvasive continuous blood pressure registration according to Penáz was used. During voluntarily controlled breathing intervals, the amplitude of 0.1 Hz and respiratory peaks in the spectra of heart rate and blood pressure changed markedly. Nevertheless, the average sensitivity of the baroreflex (modulus) changed insignificantly. This result indicated that the stability of BRS can be advantageous for the use of BRS in clinical practice. The difference between the modulus at 0.1 Hz and at the breathing rate indicates that baroreflex is only one of the factors causing respiratory arrhythmia. We also compared the determination of BRS by spectral analysis with the following alternative method: both lower extremities were occluded for 5 minutes. The release of pressure in the occluding cuffs decreased blood pressure which was followed by a baroreceptor-mediated increase of heart rate. Both methods correlated, but more detailed analysis revealed the role of the low pressure receptors in BRS determined by spectral analysis.     

Cyclooxygenase inhibition and baroreflex sensitivity in humans

Animal studies suggest that prostanoids (i.e., such as prostacyclin) may sensitize or impair baroreceptor and/or baroreflex responsiveness depending on the site of administration and/or inhibition. We tested the hypothesis that acute inhibition of cyclooxygenase (COX), the rate-limiting enzyme in prostanoid synthesis, impairs baroreflex regulation of cardiac period (R-R interval) and muscle sympathetic nerve activity (MSNA) in humans and augments pressor reactivity. Baroreflex sensitivity (BRS) was determined at baseline (preinfusion) and 60 min after (postinfusion) intravenous infusion of a COX antagonist (ketorolac; 45 mg) (24 +/- 1 yr; n = 12) or saline (25 +/- 1 yr; n = 12). BRS was assessed by using the modified Oxford technique (bolus intravenous infusion of nitroprusside followed by phenylephrine). BRS was quantified as the slope of the linear portion of the 1) R-R interval-systolic blood pressure relation (cardiovagal BRS) and 2) MSNA-diastolic blood pressure relation (sympathetic BRS) during pharmacological changes in arterial blood pressure. Ketorolac did not alter cardiovagal (19.4 +/- 2.1 vs. 18.4 +/- 2.4 ms/mmHg preinfusion and postinfusion, respectively) or sympathetic BRS (-2.9 +/- 0.7 vs. -2.6 +/- 0.4 arbitrary units.beat(-1).mmHg(-1)) but significantly decreased a plasma biomarker of prostanoid generation (plasma thromboxane B2) by 53 +/- 11%. Cardiovagal BRS (21.3 +/- 3.8 vs. 21.2 +/- 3.0 ms/mmHg), sympathetic BRS (-3.4 +/- 0.3 vs. -3.2 +/- 0.2 arbitrary units.beat(-1).mmHg(-1)), and thromboxane B2 (change in -1 +/- 12%) were unchanged in the control (saline infusion) group. Pressor responses to steady-state incremental (0.5, 1.0, and 1.5 microg.kg(-1).min(-1)) infusion (5 min/dose) of phenylephrine were not altered by ketorolac (n = 8). Collectively, these data indicate that acute pharmacological antagonism of the COX enzyme does not impair BRS (cardiovagal or sympathetic) or augment pressor reactivity in healthy young adults.     

Aldosterone impairs baroreflex sensitivity in healthy adults

Animal studies suggest that acute and chronic aldosterone administration impairs baroreceptor/baroreflex responses. We tested the hypothesis that aldosterone impairs baroreflex control of cardiac period [cardiovagal baroreflex sensitivity (BRS)] and muscle sympathetic nerve activity (MSNA, sympathetic BRS) in humans. Twenty-six young (25 +/- 1 yr old, mean +/- SE) adults were examined in this study. BRS was determined by using the modified Oxford technique (bolus infusion of nitroprusside, followed 60 s later by bolus infusion of phenylephrine) in triplicate before (Pre) and 30-min after (Post) beginning aldosterone (experimental, 12 pmol.kg(-1).min(-1); n = 10 subjects) or saline infusion (control; n = 10). BRS was quantified from the R-R interval-systolic blood pressure (BP) (cardiovagal BRS) and MSNA-diastolic BP (sympathetic BRS) relations. Aldosterone infusion increased serum aldosterone levels approximately fourfold (P < 0.05) and decreased (P < 0.05) cardiovagal (19.0 +/- 2.3 vs. 15.6 +/- 1.7 ms/mmHg Pre and Post, respectively) and sympathetic BRS [-4.4 +/- 0.4 vs. -3.0 +/- 0.4 arbitrary units (AU).beat(-1).mmHg(-1)]. In contrast, neither cardiovagal (19.3 +/- 3.3 vs. 20.2 +/- 3.3 ms/mmHg) nor sympathetic BRS (-3.8 +/- 0.5 vs. -3.6 +/- 0.5 AU.beat(-1).mmHg(-1)) were altered (Pre vs. Post) in the control group. BP, heart rate, and MSNA at rest were similar in experimental and control subjects before and after the intervention. Additionally, neural and cardiovascular responses to a cold pressor test and isometric handgrip to fatigue were unaffected by aldosterone infusion (n = 6 subjects). These data provide direct experimental support for the concept that aldosterone impairs baroreflex function (cardiovagal and sympathetic BRS) in humans. Therefore, aldosterone may be an important determinant/modulator of baroreflex function in humans.     

Decreased baroreflex sensitivity in acute schizophrenia.

Decreased vagal activity has been described in acute schizophrenia and might be associated with altered cardiovascular regulation and increased cardiac mortality. The aim of this study was to assess baroreflex sensitivity in the context of psychopathology. Twenty-one acute, psychotic, unmedicated patients with a diagnosis of paranoid schizophrenia were investigated after admission to the hospital. Results were compared with 21 healthy volunteers matched with respect to age and sex. Cardiovascular parameters obtained included measures for heart rate variability, baroreflex sensitivity, as well as cardiac output, left ventricular work index, and total peripheral resistance. All parameters investigated were analyzed using linear and novel nonlinear techniques. Positive and negative symptoms were assessed to estimate the impact of psychopathology on autonomic parameters. Subjects with acute schizophrenia showed reduction of baroreflex sensitivity accompanied by tachycardia and greatly increased left ventricular work index. Nonlinear parameters of baroreflex sensitivity correlated with positive symptoms. For heart rate variability, mainly parameters indicating parasympathetic modulation were decreased. Vascular pathology could be excluded as a confounding factor. These results reflect a dysfunctional cardiovascular regulation in acute schizophrenic patients at rest. The changes are similar to adaptational regulatory processes following stressful mental or physical tasks in healthy subjects. This study suggests that hyperarousal in acute schizophrenia is accompanied by decreased efferent vagal activity, thus increasing the risk for cardiovascular mortality. Future studies are warranted to examine the role of the sympathetic system and possible autonomic differences in hyperarousal induced by anxiety and/or external stressful events.     

Time course and auxin sensitivity of cortical microtubule reorientation in maize roots

Summary The kinetics of MT reorientation in primary roots ofZea mays cv. Merit, were examined 15,30,45, and 60 min after horizontal positioning. Confocal microscopy of longitudinal tissue sections showed no change in MT orientation 15 and 30 min after horizontal placement. However, after 45 and 60 min, MTs of the outer 4–5 cortical cell layers along the lower side were reoriented. In order to test whether MT reorientation during graviresponse is caused by an auxin gradient, we examined the organization of MTs in roots that were incubated for 1 h in solutions containing 10^–9 to 10^–6M IAA. IAA treatment at 10^–8M or less showed no major or consistent changes but 10^–7 M IAA resulted in MT reorientation in the cortex. The auxin effect does not appear to be acid-induced since benzoic acid (10^–5M) did not cause MT reorientation. The region closest to the maturation zone was most sensitive to IAA. The data indicate that early stages of gravity induced curvature occur in the absence of MT reorientation but sustained curvature leads to reoriented MTs in the outer cortex. Growth inhibition along the lower side of graviresponding roots appears to result from asymmetric distribution of auxin following gravistimulation.Abbreviations EGTA ethylene glycol-bis(-aminoethyl ether) N,N,NN-tetraacetic acid - MTs cortical microtubules - QC quiescent center - MES/TRIS 2-(N-morpholino)ethanesulfonic acid/tris(hydroxymethyl)aminomethane - IAA indole-3-acetic acid - PBS phosphate buffered saline - PHEMD [60 mM Pipes (piperazine-diethanesulfonic acid), 25 mM Hepes (N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid), 10 mM EGTA, 2mM MgCl₂ pH7.0 adjusted with NaOH] containing 5% dimethyl sulfoxide