Left atrial receptors in arterial baroreflex control of heart rate

We have studied the influence of left atrial receptor stimulation on arterial baroreflex control of heart rate with a view to determine the role of cardiac efferent sympathetic and parasympathetic pathways in any interaction observed. Experiments were performed on anaesthetized, artificially ventilated, and thoracotomised cats and dogs. The sensitivity of baroreflex heart rate response was found to be higher in dogs as compared to cats. Both the sympathetic and parasympathetic effects contributed to the reflex chronotropic effects observed during changes in mean arterial blood pressure. The reflex tachycardia response during left atrial receptor stimulation was more pronounced in dogs than in cats. Stimulation of left atrial receptors caused slight inhibition of the baroreflex tachycardia response and potentiation of the bradycardia response.     

Reversibility of abnormal arterial baroreflex control of heart rate in heart failure

The reversibility of the abnormalities in arterial baroreceptor control of heart rate in heart failure was examined in an experimental model of canine high-output biventricular failure produced by an arteriovenous fistula that could be later surgically corrected by ligation. Marked attenuation of arterial baroreceptor control of heart rate in response to both hypertensive and hypotensive stimuli was seen in this model of heart failure. After surgical correction the heart rate response to a hypertensive stimulus did not return to normal but remained severely blunted for up to 8 mo of follow-up. The lack of reversibility after surgical correction suggests that permanent structural changes in arterial baroreceptors may occur after heart failure of short duration.     

Effect of posture on arterial baroreflex control of heart rate in humans

Summary Altered baroreflex function may contribute to the cardiovascular changes associated with weightlessness. Since central blood volume (CBV) increases during simulated weightlessness, we have examined the possibility that acute changes in CBV may modify baroreceptor function. We used graded head-up tilt (HUT) and head-down tilt (HDT) to induce changes in CBV, and neck suction to stimulte carotid baroreceptors, in 6 subjects. The increase in pulse interval induced by a negative pressure of 8.2 kPa (62 mm Hg) imposed for 10 s while supine was compared with the increase while tilted for 8 min at ± 15, ± 30 and ± 45. During HDT at 15 the pulse interval over the first 5 cardiac cycles following suction onset was 51 ± (SEM) 18 ms longer (p<0.05), at 30 it was 61±20 ms longer (p<0.05), and at 45 it was 74±35 ms longer (p<0.01), compared with supine. During HUT at 15 the pulse interval was 25±9 ms shorter (p<0.05) than when supine, but was not significantly different at 30 and 45. These responses occurred independently of changes in brachial blood pressure. Attenuation was also observed after 5 min (56±17 ms; <0.05), and after 40 min (25±9 ms; p<0.05) of 60 HUT compared with supine. We conclude that posture does modify arterial baroreflex control of heart rate. If this occurs primarily as a result of a change in CBV, then the acute effect of weightlessness may be an accentuation, not an attenuation, of baroreflex function.M. H. Harrison was a National Research Council postdoctoral research fellow on leave from the Ministry of Defence, UK     

Effect of central venous pressure on arterial baroreflex control of heart rate.

There is considerable evidence that the level of afferent cardiopulmonary receptor activity modulates sinus node responses to arterial baroreflex stimulation in experimental animals. We tested the hypothesis that this reflex interaction occurs also in man by measuring sinus node responses to arterial baroreceptor stimulation with phenylephrine injection or neck suction, before and during changes of central venous pressure provoked by lower body negative pressure or leg and lower trunk elevation. Variations of central venous pressure between 1.1 and 9.0 mmHg did not influence arterial baroreflex mediated bradycardia. Baroreflex sinus node responses were augmented by intravenous propranolol, but the level of responses after propranolol was comparable during the control state, lower body negative pressure, and leg and trunk elevation. Sinus node responses to very brief baroreceptor stimuli applied during the transitions of central venous pressure also were comparable in the three states. We conclude that physiological variations of central venous pressure do not influence sinus node responses to arterial baroreceptor stimulation in man.     

Spontaneous arterial baroreflex control of the heart rate during head-down tilt in heat-stressed humans

The purpose of this study was to elucidate the effect of raised body temperature per se during acute heat stress on the spontaneous arterial baroreflex control of heart rate (f _c) in humans. To investigate whether unloading of cardiopulmonary baroreceptors during whole-body heating would alter the arterial baroreflex control of f _c, we controlled loading of the cardiopulmonary baroreceptors by head-down tilt (HDT) at angles of 5°, 10°, 15°, and 30° during heat stress produced by hot-water-perfused suits. The sensitivity of the arterial baroreceptor-cardiac reflex was calculated from the spontaneous changes in beat-to-beat arterial pressure and f _c. As an index of cardiopulmonary baroreceptor loading, the left atrial diameter (LAD) was measured by echocardiography. During whole-body heating, the LAD decreased with the rising body core temperature and increased with the HDT. The decreased LAD during heating almost recovered to the normothermic control level by 10° HDT. In the supine position, cardiac baroreflex sensitivity remained unchanged during heating. Arterial pressure, f _c and cardiac baroreflex sensitivity were not changed by HDT ranging from 5° to 30° during heating. These results suggest that cardiac baroreflex sensitivity remain unchanged during graded loading of the cardiopulmonary baroreceptors in heat-stressed humans. Also, we conclude that the sensitivity of the spontaneous arterial baroreflex controlling the f _c is not influenced by raised body temperature per se during acute heat stress. Electronic Publication     

Effect of enflurane on the baroreflex control of heart rate in decerebrate rats

Volatile anesthetics alter the arterial baroreflex (BRX) but its mechanisms are poorly understood. This study was designed to determine the effect of 1 and 2 minimal alveolar concentrations (MAC) of enflurane on the BRX parameters in unanesthetized brain stem-intact and decerebrate rats. Under enflurane anesthesia, the femoral artery and both femoral vein were catheterized for pressor (phenylephrine) and depressor (nitroprusside) drug delivery and continuous blood pressure measurements. Decerebration was performed at midcollicular level. BRX tests were performed in 3 time periods; before enflurane (conscious brain-intact), during 1 or 2 MAC enflurane exposure 1 hour after a sham operation or a decerebration operation, and 2 hours after the termination of enflurane (zero enflurane). Mean arterial pressure (MAP) and heart rate (HR) were fitted to a sigmoid logistic equation, the Boltzman equation. The curve of best fit was obtained with a computer program. 1 MAC and 2 MAC of enflurane shifted MAP-HR baroreflex curves to the left in the all groups and significantly attenuated the baroreflex range. The slope of conscious intact period and zero enflurane period of each group did not change significantly, but during the enflurane period the slope was significantly lowered. Enflurane depressed the baroreflex sensitivity (slope) and the HR range in a similar dose-dependent manner in both brain stem-intact and decerebrate rats. Such results draw into question whether the suprapontine sites contribute to enflurane's actions on cardiovascular autonomic regulation.     

Renin and heart rate responses to haemorrhage are age dependent in conscious lambs

The present experiments were carried out in conscious lambs (1-2 weeks old, n = 9) and older sheep (11-12 weeks old, n = 11) to determine whether the cardiovascular and endocrine responses to 0, 10 and 20 % haemorrhage were developmentally regulated. The major novel finding of our study is that throughout the first 3 months of postnatal life, there is a similar decrease in mean arterial pressure and a similar restoration of pressure to pre-haemorrhage levels, for the same degree of blood loss, yet the mechanisms used to restore pressure appear to be age dependent as follows. In lambs, but not in older sheep, heart rate increased for 1 h after 20% haemorrhage. Activation of the renin-angiotensin system was also greater and more prolonged in lambs than in older sheep following haemorrhage, and occurred at a lesser degree of blood loss. Plasma arginine vasopressin responses to haemorrhage were, however, similar in both age groups. These data provide new information that some of the mechanisms used to restore arterial pressure following blood volume depletion appear to be age dependent.     

Baroreceptor control of heart rate in the conscious toad Bufo marinus

Perivascular balloons were used to elicit heart rate (HR) responses to imposed changes in mean arterial pressure (Pa) in conscious unrestrained toads (Bufo marinus). It is clear that functional baroreceptors lie in the pulmocutaneous arteries of B. marinus, and that these can elicit compensatory heart rate responses to perturbations of blood pressure. Functional baroreceptors were not present in the carotid circulation and are probably absent from the lateral aortae and conus arteriosus as well. Normalized gain of the baroreceptor-heart rate reflex (delta HR%/delta Pa) in five toads was 13%/kPa, which is considerably less than that found in other vertebrates to date.     

Intrathecal kynurenate reduces arterial pressure, heart rate and baroreceptor-heart rate reflex in conscious rats

In the present study, an excitatory amino acid (EAA) pathway in the spinal cord which maintains sympathetic vasomotor tone in conscious rats has been investigated. To this end, the cardiovascular effects of an intrathecally administered EAA antagonist, kynurenate (KYN), were studied in conscious rats. KYN (0.5 mumol in 10 microliters) caused a dramatic reduction in mean arterial pressure (MAP) and heart rate (HR) that persisted for 2-3 h, and also resulted in extensor paralysis of the hindlimbs. The time courses of fall in MAP and HR and hindlimb paralysis were similar. Baroreceptor-HR reflex activity was also markedly impaired after KYN, suggesting functional diminution of sympathetic outflow at the level of the spinal cord after blockade of EAA receptors by KYN. Xanthurenate, a metabolite of KYN without EAA antagonistic properties, produced negligible effects at the same dose of KYN. While these findings do not identify the putative EAA pathway, they do provide the first demonstration that this system is tonically active in conscious rats.     

Thermal stress modulates arterial pressure variability and arterial baroreflex response of heart rate during head-up tilt in humans

To examine the effects of thermal stress on the blood pressure variability and the arterial baroreceptor-cardiac reflex during orthostatic stress, 11 male volunteers underwent whole body thermal stress using a cool or hot water-perfused suit during 5 min of 70° head-up tilt (HUT). The spontaneous variability in arterial pressure was quantified by power spectrum analysis. The sensitivity of the arterial baroreceptor-cardiac reflex was calculated from the spontaneous changes in beat-to-beat arterial pressure and heart rate (f _c). During supine rest the variability of arterial pressure decreased during cooling, while it remained unchanged during heating. The variability increased with HUT; it was greater (P<0.05) with heating than with cooling. In the supine condition, the arterial baroreflex sensitivity of f _c increased during cooling, while it did not change during heating. The sensitivities decreased (P<0.05) with HUT during both thermal stresses; the decreased rate of sensitivity from the pre-tilt value was greater during heating [mean 63 (SEM 4)%] and smaller during cooling [mean 11 (SEM 24)%] than during normothermia [mean 47 (SEM 4)%] (both, P<0.05). There were significant negative correlations between the sensitivities and the amplitude of the arterial pressure variability during normothermia and heating (P<0.0001). The results suggest that the spontaneous baroreflex response of f _c is a modulatory factor for the changes of arterial pressure variability brought about by thermal stress during orthostatic stress. Electronic Publication     

Central and baroreflex control of heart rate during the wake-sleep cycle in rat.

Spontaneous fluctuations in Heart Period (HP) and Mean Arterial Pressure (MAP) make it possible to evaluate baroreceptor-heart rate reflex sensitivity (BRS). 30-s sequences of HP and MAP beat-to-beat values were considered in the different wake-sleep states (Wake, W; Quiet Sleep, QS; Active Sleep, AS) in rats to assess whether 1) BRS changes between states and 2) the different indexes supply consistent BRS measures. BRS indexes were calculated according to validated literature procedures as regression coefficients of HP vs. MAP 1) within all ramps of increasing or decreasing MAP of four beats or more, with HP and MAP changing in the same direction (baroreflex-mediated fluctuations, BRSp), 2) within all such ramps irrespective of the relative direction of HP and MAP changes (baroreflex + non-baroreflex, i.e. non-homeostatic centrally driven, fluctuations, BRSA). HP vs. MAP regression coefficient along the entire 30-s sequence (bHPMAP) was also calculated. RESULTS: BRSp did not change among states, BRSA decreased from QS to W to AS, bHPMAP decreased from QS to W and became negative in AS. CONCLUSIONS: 1) as indicated by BRSp, baroreflex sensitivity is state independent, 2) BRSp to BRS(A) to bHPMAP are increasingly affected by non-baroreflex fluctuations, BRSp being most apt to measure BRS, 3) non-homeostatic MAP and HP fluctuations increase from QS to W and prevail in AS. These potentially harmful fluctuations are normally buffered by baroreflexes: in the case of baroreflex impairment, circulatory risk may arise in conditions like AS, when they prevail.     

Central antioxidant therapy inhibits parasympathetic baroreflex control in conscious rats

Baroreceptor reflex is an important system for neural control of blood pressure. Recently, reactive oxygen species (ROS) have been shown to play an important role in neuronal activity of central areas related to blood pressure control. The aim of this study was to investigate the effects elicited by ascorbic acid (AAC) and N-acetylcysteine (NAC) injections into the 4thV on the parasympathetic component of the baroreflex. Male Wistar rats were implanted with a stainless steel guide cannula into the 4thV. One day prior to the experiments, the femoral artery and vein were cannulated for pulsatile arterial pressure, mean arterial pressure and heart rate measurements and drug administration, respectively. After baseline recordings, the baroreflex was tested with a pressor dose of phenylephrine (PHE, 3 μg/kg, i.v.) and a depressor dose of sodium nitroprusside (SNP, 30 μg/kg, i.v.) before (control) and 5, 15, 30 and 60 min after AAC or NAC into the 4thV. Control PHE injection induced baroreflex-mediated bradycardia (-93 ± 13 bpm, n=7). Interestingly, after AAC injection into the 4thV, PHE injection produced a transient tachycardia at 5 (40 ± 23 bpm), 15 (26 ± 22 bpm) and 30 min (59 ± 21 bpm). No changes were observed in baroreflex-mediated tachycardia evoked by SNP after AAC injection on 4thV (control: 151 ± 23bpm vs. 135 ± 18 bpm at 5 min after AAC, n=7). In the NAC treated group, PHE induced a reduction in reflex bradycardia at 5 min when compared to control (-11 ± 17 bpm vs. -83 ± 15 bpm, n=7). No changes were observed in baroreflex-mediated tachycardia evoked by SNP after NAC injection on 4thV. The antioxidants AAC and NAC may act in the central nervous system affecting the parasympathetic component of the cardiac baroreflex.     

运动训练改善心力衰竭大鼠动脉压力反射功能

目的:探讨运动训练(EX)对慢性心力衰竭(CHF)大鼠动脉压力反射功能的影响及机制。方法:实验分4组:心衰-运动组(EX-CHF),心衰-非运动组(CHF),假手术-运动组(EX-sham),假手术-非运动组(sham)。采用结扎左冠状动脉诱发心衰,然后进行4周跑步运动,检测压力反射(BR)、血浆血管紧张素II(AngII)和中枢AngIIⅠ型受体(AT1R)表达。结果:(1)CHF大鼠BR曲线平均斜率和最大增益明显小于sham大鼠(P0.01),EX增强CHF大鼠BR曲线平均斜率和最大增益(P0.05),但对sham组BR曲线无明显影响。(2)EX降低CHF大鼠血浆AngII浓度[(137±27)ng/Lvs(263±55)ng/L,P0.01],但不影响sham大鼠血浆AngII[(75±17)ng/Lvs(92±21)ng/L]。(3)CHF大鼠PVN内AT1R蛋白表达明显高于sham组(1.20±0.21vs0.70±0.14,P0.01),EX显著降低CHF大鼠室旁核内AT1R蛋白表达(0.90±0.13,P0.05),对sham大鼠AT1R表达(0.60±0.16)无明显影响。结论:运动训练改善心衰时减弱的动脉压力反射功能,其机制涉及降低血浆AngII和下调室旁核内AT1R蛋白表达。     

Effect of hypothermia on baroreflex control of heart rate and renal sympathetic nerve activity in anaesthetized rats

The present study investigated the effect of acute hypothermia on baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) by generating baroreflex logistic function curves, using bolus doses of phenylephrine and sodium nitroprusside, in anaesthetized male Wistar rats at a core temperature ( T _b) of 37°C, during acute severe hypothermia at T _b= 25°C and on rewarming to 37°C. Comparisons were made between rats without (euthermic, n = 6) and with (acclimated, n = 7) prior exposure to lower ambient temperatures and shorter photoperiod, simulating adaptation to winter conditions. In both groups of rats, acute hypothermia to T _b= 25°C shifted the baroreflex-RSNA curve slightly leftwards and downwards with decreases in the setpoint pressure and maximal gain, whereas it markedly impaired the baroreflex-HR curve characterized by decreases in response range by ∼90% ( P < 0.001), minimum response by ∼10% ( P < 0.05) and maximum gain by ∼95% ( P < 0.001), from that at T _b= 37°C. All parameters were restored to precooling levels on rewarming. Electrical stimulation of cardiac vagal efferents induced a voltage-related bradycardia, the magnitude of which was partially reduced during acute hypothermia, and there was a significant prolongation of the electrocardiogram intervals indicating a delay in cardiac conduction. Mild suppression of baroreflex control of RSNA could contribute to hypothermic hypotension and may primarily reflect an effect of T _b on central drive. The marked attenuation of the baroreflex control of HR during hypothermia was likely to be due to an impairment of both the central and peripheral components of the reflex arc. Baroreflex control of RSNA and HR was similar between both groups of rats, which implied that the control was non-adaptive on chronic cold exposure.     

The vagal cardiac accelerator system in the reflex control of heart rate in conscious dogs

The reactions of the vagal cardioaccelerator (VCA) system to changes in mean arterial pressure (MAP) were studied in five beta-adrenoceptor blocked conscious dogs. An increase in MAP was obtained by administration of vasopressin or methoxamine, a decrease by doxazosin or nitroprusside. In the first series of experiments the MAP changes were induced after muscarinic receptor blockade, in a second series both before and after muscarinic blockade. Prior to these experiments, the maximum VCA activity, defined as the difference between maximum heart rate after muscarinic blockade and the rate after additional nicotinic blockade, was determined. We hypothesized that this quantity, as a measure of VCA activity, depends on the prevailing vagal tone. In the first series of experiments, a rise in MAP evoked an increase in heart rate, a fall in MAP indicated decrease. In the second series, when prior to muscarinic blockade the vagal tone was reflexly raised, the subsequent VCA reflex response to the rise in MAP was attenuated. Prior to the muscarinic blockade the vagal tone was reflexly lowered, the VCA reflex response was enhanced. Direct chronotropic effects of MAP-varying drugs were ruled out by the absence of a heart-rate response in experiments on vagotomized animals. We concluded that the vagal cardioaccelerator system is involved in the reflex control of heart rate. Both the VCA reflex response to changes in systemic blood pressure and the maximum VCA activity however, are determined by the prevailing vagal tone.     

Beta-adrenergic control and inter-relationships between heart rate and blood pressure in neonatal lambs

Our aim was to develop a signal analysis method for revealing interrelationships between heart rate and blood pressure and for displaying the influence of autonomic nervous control on these signals in a chronic lamb model. A chronically instrumented neonatal lamb model was made to record ECG and direct arterial blood pressure (N=15). Continuous two-minute recordings of blood pressure (BP) and ECG were digitised. The instantaneous heart rate signal (IHR) was derived from the ECG. The IHR and BP signals were bandpass filtered. Autospectra, cross-spectra, coherence spectra and phase spectra for the signals were computed to study the relative magnitudes and inter-relationships of the cardiovascular signals under normal conditions and during beta-adrenergic blockade. It was noted that both in the BP and IHR there were oscillations at the frequency of <0·1 Hz and also at the respiratory rate around 0·6 Hz. Beta-blockade reduced the oscillations of the IHR in <30-day-old lambs. It did not affect the coherence spectra or the phase lag between the signals. During quiet sleep the variability of blood pressure was decreased. In over-30-day-old-lambs the beta-blockade did not affect the variabilities of the cardiovascular parameters. These findings indicate that in neonatal lambs the sympathetic control system is a major regulator of cardiovascular interactions.     

High levels of circulating angiotensin II shift the open-loop baroreflex control of splanchnic sympathetic nerve activity,heart rate and arterial pressure in anesthetized rats

Although an acute arterial pressure (AP) elevation induced by intravenous angiotensin II (ANG II) does not inhibit sympathetic nerve activity (SNA) compared to an equivalent AP elevation induced by phenylephrine, there are conflicting reports as to how circulating ANG II affects the baroreflex control of SNA. Because most studies have estimated the baroreflex function under closed-loop conditions, differences in the rate of input pressure change and the magnitude of pulsatility may have biased the estimation results. We examined the effects of intravenous ANG II (10 μg kg⁻¹ h⁻¹) on the open-loop system characteristics of the carotid sinus baroreflex in anesthetized and vagotomized rats. Carotid sinus pressure (CSP) was raised from 60 to 180 mmHg in increments of 20 mmHg every minute, and steady-state responses in systemic AP, splanchnic SNA and heart rate (HR) were analyzed using a four-parameter logistic function. ANG II significantly increased the minimum values of AP (67.6 ± 4.6 vs. 101.4 ± 10.9 mmHg, P < 0.01), SNA (33.3 ± 5.4 vs. 56.5 ± 11.5%, P < 0.05) and HR (391.1 ± 13.7 vs. 417.4 ± 11.5 beats/min, P < 0.01). ANG II, however, did not attenuate the response range for AP (56.2 ± 7.2 vs. 49.7 ± 6.2 mmHg), SNA (69.6 ± 5.7 vs. 78.9 ± 9.1%) or HR (41.7 ± 5.1 vs. 51.2 ± 3.8 beats/min). The maximum gain was not affected for AP (1.57 ± 0.28 vs. 1.20 ± 0.25), SNA (1.94 ± 0.34 vs. 2.04 ± 0.42%/mmHg) or HR (1.11 ± 0.12 vs. 1.28 ± 0.19 beats min⁻¹ mmHg⁻¹). It is concluded that high levels of circulating ANG II did not attenuate the response range of open-loop carotid sinus baroreflex control for AP, SNA or HR in anesthetized and vagotomized rats.     

Respiratory sinus arrhythmia and carotid baroreflex control of heart rate in endurance athletes and untrained controls

The purpose of this study was to compare the magnitude of the respiratory sinus arrhythmia, an index of cardiac vagal tone, and carotid baroreflex control of heart rate in endurance-trained athletes (n = 12, aged 20 +/- 1 years, means +/- SE) and untrained control subjects (n = 12, aged 22 +/- 1 year). Average R-R interval (ECG) and its variability were determined at rest under controlled breathing conditions, and the changes in R-R interval in response to brief applications of suction (-10, -25, -40 mmHg) and pressure (10 and 30 mmHg) to the carotid sinus region of the neck were also measured. The average R-R interval at rest was greater in the athletes vs. controls (1150 +/- 45 vs. 854 +/- 44 ms, P less than 0.001), but the standard deviation of the R-R intervals was similar in the two groups (72 +/- 15 vs. 70 +/- 9 ms). The magnitude of the tachycardia in response to neck pressure was also similar in the athletes and controls. Although the heart rate responses to neck suction were not significantly different between the two groups, there was a strong trend for attenuated bradycardic responses in the athletes at the two highest stimulus levels (70 +/- 14 vs. 97 +/- 25 ms and 86 +/- 14 vs. 145 +/- 38 ms for the -25 and -40 mmHg levels, respectively, P greater than 0.1). The results of this study do not support the postulate that cardiac vagal tone is enhanced in the endurance-trained state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Summation of baroreflex and classically conditioned heart rate responses in dogs

Following instrumentation with pneumatic cuffs around the inferior vena cava and the descending aorta, dogs were studied either following differential classical conditioning or in a control state. The cuffs functioned to raise and lower blood pressure for the construction of baroreflex curves for heart rate. Conditioned dogs received 8 trials each day with each CS+ (tone paired with flank shock) and CS- (a different tone without shock). Curves were constructed from cuff inflations timed to coincide with the maximum conditioned heart rate response. These curves were constructed from data acquired during infusion of saline, methyl atropine, or propranolol. Comparison of these curves revealed that the CS+ shifted the curves toward higher heart rates while the CS- curve was shifted toward lower heart rates without a change in gain. The amount of shift was comparable to that of the conditioned heart rate response. This suggested that the responses were independent and additive. Neither propranolol nor atropine eliminated this separation between the curves induced by the conditioning. These observations lead us to conclude that classically conditioned stress and baroreceptor stimulation exert independent control over heart rate that are mediated by both sympathetic and parasympathetic influences.