Bezold-Jarisch reflex blunts arterial baroreflex via the shift of neural arc toward lower sympathetic nerve activity

Although the Bezold-Jarisch (BJ) reflex is potentially evoked during acute myocardial ischemia or infarction, its effects on the static characteristics of the arterial baroreflex remain to be analyzed in terms of an equilibrium diagram between the neural and peripheral arcs. The neural arc represents the static input-output relationship between baroreceptor pressure input and efferent sympathetic nerve activity (SNA), whereas the peripheral arc represents that between SNA and arterial pressure (AP). In 8 anesthetized rabbits, we increased carotid sinus pressure stepwise from 40 to 160 mmHg in increments of 20 mmHg at one-minute intervals while measuring renal SNA and AP under control conditions and during the activation of the BJ reflex by intravenous administration of phenylbiguanide (PBG, 100 microg.kg(-1).min(-1)). The neural arc approximated a sigmoid curve whereas the peripheral arc approximated a straight line. PBG decreased AP at the operating point from -91.3 +/- 2.4 to -71.7 +/- 3.1 mmHg (P < 0.01), and attenuated the total loop gain at the operating point from -1.31 +/- 0.44 to -0.51 +/- 0.14 (P < 0.05). The equilibrium diagram indicated that PBG caused a parallel shift of the neural arc toward lower SNA such that the maximum SNA was reduced to approximately 60% of control. PBG decreased neural and peripheral arc gains at the operating point to approximately 43% and 77%, respectively. In conclusion, the BJ reflex blunts arterial baroreflex via the shift of the neural arc toward lower SNA.     

Closed-loop identification of carotid sinus baroreflex transfer characteristics using electrical stimulation

Although random aortic pressure (AOP) perturbation according to a binary white noise sequence enables us to estimate open-loop dynamic characteristics of the carotid sinus baroreflex under closed-loop conditions, the necessity of arterial catheter implantation limits the applicability of this method in freely moving animal experiments. Thus, we explored a closed-loop system identification method using electrical stimulation. In 6 anesthetized and vagotomized rabbits, we stimulated the aortic depressor nerve with a binary white noise sequence (0-10 Hz) under baroreflex closed-loop conditions while measuring cardiac sympathetic nerve activity (SNA) and AOP. We used a closed-loop identification method to estimate the peripheral arc transfer function from SNA to AOP. The peripheral arc transfer function approximated a second-order low-pass filter and its fitted parameters did not differ from those obtained by an open-loop identification method (dynamic gain: 1.16+/-0.32 vs. 1.02+/-0.11; natural frequency: 0.08+/-0.03 vs. 0.09+/-0.03 Hz; damping ratio: 1.53+/-0.15 vs. 1.57+/-0.21). In 6 different rabbits, we applied intermittent rapid pacing (396 beats/min) under baroreflex closed-loop conditions to estimate the neural arc transfer function from AOP to SNA. The neural arc transfer function approximated a first-order high-pass filter and its fitted parameters did not differ from those obtained by an open-loop identification method (dynamic gain: -1.15+/-0.45 vs. -1.06+/-0.05; corner frequency: 0.12+/-0.05 vs. 0.13+/-0.03 Hz). In conclusion, the closed-loop identification method using electrical stimulation is effective to estimate the neural and peripheral arc transfer functions.     

Upright tilt resets dynamic transfer function of baroreflex neural arc to minify the pressure disturbance in total baroreflex control

Maintenance of arterial pressure (AP) under orthostatic stress against gravitational fluid shift and pressure disturbance is of great importance. One of the mechanisms is that upright tilt resets steady-state baroreflex control to a higher sympathetic nerve activity (SNA). However, the dynamic feedback characteristics of the baroreflex system, a hallmark of fast-acting neural control, remain to be elucidated. In the present study, we tested the hypothesis that upright tilt resets the dynamic transfer function of the baroreflex neural arc to minify the pressure disturbance in total baroreflex control. Renal SNA and AP were recorded in ten anesthetized, vagotomized and aortic-denervated rabbits. Under baroreflex open-loop condition, isolated intracarotid sinus pressure (CSP) was changed according to a binary white noise sequence at operating pressure +/- 20 mmHg, while the animal was placed supine and at 60 degrees upright tilt. Regardless of the postures, the baroreflex neural (CSP to SNA) and peripheral (SNA to AP) arcs showed dynamic high-pass and low-pass characteristics, respectively. Upright tilt increased the transfer gain of the neural arc (resetting), decreased that of the peripheral arc, and consequently maintained the transfer characteristics of total baroreflex feedback system. A simulation study suggests that postural resetting of the neural arc would significantly increase the transfer gain of the total arc in upright position, and that in closed-loop baroreflex the resetting increases the stability of AP against pressure disturbance under orthostatic stress. In conclusion, upright tilt resets the dynamic transfer function of the baroreflex neural arc to minify the pressure disturbance in total baroreflex control.     

Baroreflex “resetting” by arterial hypoxia in the renal and cardiac sympathetic nerves of the rabbit

1. Renal and cardiac sympathetic baroreflex functions were studied in sodium pentobarbitone anaesthetized rabbits given succinylcholine, during constant artificial ventilation with air and with hypoxic gas mixtures. Mean arterial pressure (MAP) was raised and lowered between values of 40 and 140 mm Hg by means of aortic and vena caval periovascular balloons and integrated sympathetic nerve activity (SNA) was recordered. 2. The relationship between MAP and SNA was sigmoid, with upper and lower plateau levels. The curves were defined by calculating median blood pressure, SNA Range and reflex gain. In both renal and cardiac sympathetics section of the carotid sinus and aortic nerves completely abolished the MAP-related changes in SNA. 3. The renal baroreflex curves were reset from control levels during hypoxia. Median blood pressure increased, as did SNA Range and gain. These effects were due to central interactions between arterial baroreceptor, arterial chemoreceptor and vagal afferent activity. 4. The cardiac sympathetic baroreflex curves were shifted in the opposite direction from control with reduction in median blood pressure, SNA Range and reflex gain. These changes were due to chemoreceptor-arterial baroreceptor interactions. 5. Arterial hypoxia thus evokes a differentiated pattern of baroreflex resetting in the renal and cardiac sympathetic montoneuron pools with differing changes in neural response range and sensitivity to arterial pressure changes.     

Open-loop dynamic and static characteristics of the carotid sinus baroreflex in rats with chronic heart failure after myocardial infarction

We estimated open-loop dynamic characteristics of the carotid sinus baroreflex in normal control rats and chronic heart failure (CHF) rats after myocardial infarction. First, the neural arc transfer function from carotid sinus pressure to splanchnic sympathetic nerve activity (SNA) and its corresponding step response were examined. Although the steady-state response was attenuated in CHF, the negative peak response and the time to peak did not change significantly, suggesting preserved neural arc dynamic characteristics. Next, the peripheral arc transfer function from SNA to arterial pressure (AP) and its corresponding step response were examined. The steady-state response and the initial slope were reduced in CHF, suggesting impaired end-organ responses. In a simulation study based on the dynamic and static characteristics, the percent recovery of AP was reduced progressively as the size of disturbance increased in CHF, suggesting that a reserve for AP buffering is lost in CHF despite relatively maintained baseline AP.     

Intravenous angiotensin II does not affect dynamic baroreflex characteristics of the neural or peripheral arc

Although the elevation of angiotensin II (Ang II) associated with cardiovascular diseases has been considered to suppress the arterial baroreflex function, how Ang II affects dynamic arterial pressure (AP) regulation remains unknown. The aim of the present study was to elucidate the acute effects of Ang II on dynamic AP regulation by the arterial baroreflex. In seven anesthetized Japanese white rabbits, we randomly perturbed intra-carotid sinus pressure (CSP) according to a binary white noise sequence while recording renal sympathetic nerve activity (RSNA) and AP. We estimated the neural arc transfer function from CSP to RSNA and the peripheral arc transfer function from RSNA to AP before and after 30-min intravenous administration of Ang II (100 ng/kg/min). Ang II increased mean AP from 75.7 +/- 3.1 to 95.5 +/- 5.1 mmHg (p < 0.01), while it did not affect mean RSNA (from 5.9 +/- 1.3 to 5.7 +/- 1.2 a.u.). The neural arc transfer functions did not differ before or after Ang II administration (dynamic gain: -0.94 +/- 0.04 vs. -0.94 +/- 0.13, corner frequency: 0.06 +/- 0.01 vs.0.06 +/- 0.01 Hz, pure delay: 0.16 +/- 0.01 vs. 0.17 +/- 0.02 s). The peripheral arc transfer function did not differ before or after Ang II administration (dynamic gain: 1.18 +/- 0.05 vs. 1.06 +/- 0.11, natural frequency: 0.07 +/- 0.01 vs. 0.08 +/- 0.01 Hz, damping ratio: 1.19 +/- 0.06 vs. 1.24 +/- 0.19, pure delay: 0.83 +/- 0.06 vs. 0.78 +/- 0.05 s). Intravenous Ang II hardly affects the dynamic characteristics of neural and peripheral arc around the physiological operating pressure.     

Rapid adaptation of central pathways explains the suppressed baroreflex with aging.

Aging is associated with suppressed baroreflex function. Renal sympathetic nerve activity was recorded from young (1 year) and old beagles (11 years) during a step rise in isolated carotid sinus pressure. An abrupt increase in pressure resulted in a significant and similar inhibition of efferent nerve activity in both groups, but the inhibition was not sustained in the old as compared with the young animals. The escape from sympathetic inhibition in the old could not be explained by a decline of input from sensory baroreceptor neurons. Thus the defect in the aged animals is caused by a rapid adaptation of central baroreflex neurons to the baroreceptor input instead of a lack of responsiveness of these neurons, suggesting a functional rather than a structural impairment.     

Age-related effects of vagotonic atropine on cardiovagal baroreflex gain

Impaired neural transduction of barosensory vessel stretch into vagal outflow is a primary determinant of reduced cardiovagal baroreflex gain with human aging. We set out to determine whether age-related reductions in this neural component of the baroreflex might be offset by enhancing the central integration/efferent responsiveness of the neural arc. Low vagotonic doses of atropine were employed to enhance central neural outflow and peripheral sinus node effects. Baroreflex gain and its neural and mechanical components were pharmacologically assessed before and after intravenous vagotonic atropine in 16 older and 14 young healthy subjects. Vagotonic atropine increased cardiovagal baroreflex gain (∼30%) and its neural component (∼20%) in older but not young individuals. Moreover, the atropine-induced increases in integrated gain and in its neural component were inversely related to baseline levels. Thus, age-related neural deficits in the baroreflex arc appear to play a determining role in reduced cardiovagal baroreflex gain with age and the compromised neural baroreflex function can be acutely improved by a single pharmacologic intervention.     

Resetting of the arterial baroreflex increases orthostatic sympathetic activation and prevents postural hypotension in rabbits

Since humans are under ceaseless orthostatic stress, the mechanism to maintain arterial pressure (AP) under orthostatic stress against gravitational fluid shift is of great importance. We hypothesized that (1) orthostatic stress resets the arterial baroreflex control of sympathetic nerve activity (SNA) to a higher SNA, and (2) resetting of the arterial baroreflex contributes to preventing postural hypotension. Renal SNA and AP were recorded in eight anaesthetized, vagotomized and aortic-denervated rabbits. Isolated intracarotid sinus pressure (CSP) was increased stepwise from 40 to 160 mmHg with increments of 20 mmHg (60 s for each CSP level) while the animal was placed supine and at 60 deg upright tilt. Upright tilt shifted the CSP–SNA relationship (the baroreflex neural arc) to a higher SNA, shifted the SNA–AP relationship (the baroreflex peripheral arc) to a lower AP, and consequently moved the operating point to marked high SNA while maintaining AP. A simulation study suggests that resetting in the neural arc would double the orthostatic activation of SNA and increase the operating AP in upright tilt by 10 mmHg, compared with the absence of resetting. In addition, upright tilt did not change the CSP–AP relationship (the baroreflex total arc). A simulation study suggests that although a downward shift of the peripheral arc could shift the total arc downward, resetting in the neural arc would compensate this fall and prevent the total arc from shifting downward to a lower AP. In conclusion, upright tilt increases SNA by resetting the baroreflex neural arc. This resetting may compensate for the reduced pressor responses to SNA in the peripheral cardiovascular system and contribute to preventing postural hypotension.     

Estimation of baroreflex gain using a baroreflex equilibrium diagram

Two types of closed-loop perturbations can be applied to the arterial baroreflex system. The first (P(D1)) is introduced into the baroreceptors without a direct effect on arterial pressure (AP), whereas the second (P(D2)) initially affects AP. Neck suction and hemorrhage are examples of P(D1) and P(D2), respectively. To estimate the baroreflex open-loop gain (G(Baro)) without knowing the absolute magnitudes of P(D1) and P(D2), we explored a new strategy to estimate G(Baro) by combining P(D1) and P(D2) in a baroreflex equilibrium diagram. In this diagram, the neural arc presents the input-output relationship between baroreceptor pressure input and sympathetic nerve activity (SNA). The peripheral arc presents the input-output relationship between SNA and AP. In 8 anesthetized rabbits, we estimated G(Baro) by multiplying the slopes of the peripheral arc determined from P(D1) and the neural arc determined from P(D2). We also estimated G(Baro) by a conventional open-loop analysis. The G(Baro) values estimated by the equilibrium diagram and the open-loop analysis showed a positive correlation (y = 0.80x + 0.22, r(2) = 0.95) and a standard error of estimate of 0.21 across the animals. We conclude that G(Baro) was estimated well by combining P(D1) and P(D2) in the equilibrium diagram.     

Temporal and spatial interactions between the carotid sinus and vagally mediated baroreflexes in dogs

We investigated the temporal and spatial interactions between the carotid sinus and aortic arch baroreflex control of arterial pressure in 25 dogs anesthetized with pentobarbital sodium. The carotid sinus baroreceptor region was vascularly isolated to control the intracarotid sinus pressure. A hemorrhage catheter was inserted into the aortic arch. The systemic arterial pressure change after quick mild hemorrhage (2 ml/kg body weight within 1-2 s) was monitored. The open-loop gain of the vagally mediated baroreflex system was estimated from the mean arterial pressure response to the hemorrhage. Three protocols were employed to analyze the interactions. In the first protocol, we determined the effect of different levels of intracarotid sinus pressure on the open-loop gain of the vagally mediated baroreflex system. There was no significant effect. In the second protocol, the open-loop gain of the carotid sinus baroreflex system was determined after vagotomy. In the third protocol, the vagally mediated baroreflex system was activated by the hemorrhage without (spatial interaction) or with (temporal interaction) a delay after changing the intracarotid sinus pressure. The spatial interaction was facilitatory. A temporal interaction was found between the carotid sinus and vagally mediated baroreflex systems, when the delay was less than 30 s.     

Systems analysis of the carotid sinus baroreflex system using a sum-of-sinusoidal input.

The purpose of the present study was to determine the dynamic characteristics of the carotid sinus baroreflex system (CS) employing systems analysis. In 28 anesthetized and mechanically ventilated dogs with vagotomy, intracarotid sinus pressure (ICSP) was changed artificially. In protocol 1 (n = 7), we estimated the transfer function of the CS by means of a single sinusoidal input (SIN), the Gaussian white-noise input (GWN), and a sum-of-sinusoidal input (SUM). The transfer function of ICSP to systemic arterial pressure (SAP) was second-order delay with an identical corner frequency of 0.025 Hz and damping ratio of 0.7. The steady-state gain estimated using GWN (1.12 +/- 0.13) or SUM (1.13 +/- 0.08) was significantly smaller than SIN (1.69 +/- 0.25). In protocol 2, to find the reason why there was a difference among the estimated steady-state gains, we investigated the effect of ICSP pulsation on the open-loop gain of the CS. The maximum gain of the gain curve was decreased and the operating range was increased significantly with the 2-Hz pulsation. We could simulate the above phenomena by using a model with a nonlinear sigmoidal relationship between ICSP and SAP. The dynamic characteristics of the CS appeared to be changed by pulsation, but this phenomenon was attributable to the sigmoidal nature of the relationship between ICSP and SAP. Pulsation decreases the maximum gain and increases the operating range, which may contribute to stability of the CS and homeostasis of SAP.     

Non-invasive model-based estimation of the sinus node dynamic properties from spontaneous cardiovascular variability series

A non-invasive model-based approach to the estimation of sinus node dynamic properties is proposed. The model exploits the spontaneous beat-to-beat variability of heart period and systolic arterial pressure and the sampled respiration, thus surrogating the information from direct measures of neural activity. The residual heart period variability not related to baroreflex, to direct effects of respiration and to low frequency influences independent of baroreflex, is interpreted as the effect of the dynamic properties of the sinus node and modelled as a regression of the RR interval over its previous value. Therefore the sinus node transfer function is modelled by means of a filter with a real pole z=μ (and a zero in the origin). It was found that: first, in young healthy subjects the nodal tissue responded as a lowpass filter with μ=0.76±0.12 (mean±SD); secondly, ageing did not significantly modify either its shape or gain at 0Hz; thirdly, in heart transplant recipients, the dynamic transduction properties were lost (all-pass filter, μ=0.06±0.16, p<0.001); fourthly, low-dose atropine left the sinus node dynajic properties unmodified; fifthly, high-dose atropine affected the dynamic transduction properties by increasing the gain at 0Hz and rendering steeper its roll-off (the percent increase of μ with respect to baseline was 18.3±22.3, p<0.05).     

Responses of abdominal vascular capacitance in the anaesthetized dog to changes in carotid sinus pressure.

1. The abdominal circulation of anaesthetized dogs was vascularly isolated without opening the abdomen, by cutting or tying all structures immediately above the diaphragm and tying the proximal ends of the hind limbs. The region was perfused at constant flow through the aorta and drained at constant pressure from the inferior vena cava. 2. Vascular resistance responses were expressed as the changes in perfusion pressure and capacitance responses were determined by integrating changes in vena caval outflow. 3. Decreasing the pressure in the isolated carotid sinuses over the whole baroreceptor sensitivity range increased mean perfusion pressure from 91 to 149 mmHg (a 67% increase in resistance) and decreased mean capacitance by 111 ml. (5 ml. kg-1). 4. The range of carotid sinus pressures over which capacitance responses occurred was at a significantly higher level than the corresponding range for resistance responses. 5. Comparison of the reflex responses with the responses to direct stimulation of efferent sympathetic nerves shows that quantitatively similar responses of resistance and capacitance to those induced by a large step decrease in carotid pressure could be produced by stimulating maximally the efferent sympathetic nerves at 5 Hz. These results also suggest that at all levels of carotid sinus pressure there is no difference in the impulse traffic to resistance and capacitance vessels.     

Interaction between the baroreceptor and Bezold-Jarisch reflexes

The interaction between the carotid baroreflex and Bezold-Jarisch (BJ) reflex (intravenously administered veratridine) was studied in anesthetized rabbits after aortic nerve section. The carotid sinuses were vascularly isolated to regulate the intrasinus pressure (ISP). The extent of BJ reflex bradycardia and hypotension was progressively diminished as the ISP was elevated stepwise. When the carotid baroreflex was not operative by holding the ISP constant at control, the BJ reflex changes in heart rate (HR) and systemic arterial pressure (SAP) were not significantly different from those induced at the normal condition. Thus the calculated baroreflex static loop gain was greatly decreased during the BJ reflex. However, sinus denervation, analogous to keeping ISP below 50 mmHg, significantly enhanced the BJ reflex effects. A steady-state infusion of veratridine remarkably reduced the slope of the baroreflex function ISP-SAP and ISP-HR curves. The results indicate that the BJ reflex effects are affected by the prevailing arterial baroreceptor input, varying inversely with the ISP level. An attenuation in the baroreflex sinsitivity, in terms of the loop gain or slope of the transfer function curve, was observed during the BJ reflex. The presence of tonic cardiovascular inhibitions exerted by the arterial baroreceptors tends to reduce the BJ reflex bradycardia and hypotension, but the baroreceptors do not function adequately in buffering the cardiovascular inhibition produced by the cardiogenic reflex.     

Baroreflex and somato-reflex control of blood pressure, heart rate and renal sympathetic nerve activity in the obese Zucker rat

It has been reported that the baroreflex control of heart rate (HR) and sympathetic nerve activity (SNA) is attenuated in obese Zucker rats (OZRs) compared with age-matched lean animals (LZRs). What is not known, however, is the extent to which the baroreflex control of mean arterial blood pressure (MAP) is altered in the OZR. In addition, it is not known whether the interactions of other sensory nerve inputs on autonomic control are altered in the OZR compared with the LZR. The aim of this study was to determine the baroreflex control of MAP, HR and renal SNA (RSNA) in the OZR and LZR using an open-loop baroreflex approach. In addition, the effect of brachial nerve stimulation (BNS) on the baroreflex control was determined in these animals. Age-matched, male LZRs and OZRs were anaesthetized, and the carotid baroreceptors were vascularly isolated, bilaterally. The carotid sinus pressure was increased in 20 mmHg increments from 60 to 180 mmHg using an oscillating pressure stimulus. Baroreflex function curves were constructed using a four-parameter logistic equation, and gain was calculated from the first derivative, which gave a measure of baroreceptor sensitivity, before and during BNS. The range over which the baroreflex could change MAP (28 ± 6 versus 87 ± 5 mmHg; mean ± SEM), HR (17 ± 4 versus 62 ± 11 beats min(-1)) and normalized RSNA (NormNA; 22 ± 4 versus 76 ± 11%) was significantly decreased in the OZR compared with the LZR. Likewise, the maximal gain was lower in the OZR, as follows: MAP -0.88 ± 0.22 versus -2.26 ± 0.17; HR -0.42 ± 0.18 versus -1.44 ± 0.22 beats min(-1); and NormNA -0.54 ± 0.14 versus -1.65 ± 0.30% mmHg(-1). There was no difference in the mid-point of the baroreflex curve for each variable between the OZR and LZR. However, the minimal values obtained when the baroreceptors were maximally loaded were higher in the OZR (MAP 68 ± 5 versus 53 ± 4 mmHg; HR 455 ± 7 versus 390 ± 13 beats min(-1); and NormNA -19 ± 4 versus -48 ± 8%). Brachial nerve stimulation in the LZR resulted in an upward and rightward resetting of the baroreflex control of MAP and RSNA, and abolished baroreflex control of HR. The baroreflex control of RSNA in the OZR during BNS was further attenuated and reset upwards and to the right, while the HR response was abolished. With respect to MAP, the baroreflex curve reset upwards and to the right to a point comparable with the LZR during BNS. These data show that there is an attenuated baroreflex control in the OZR and that the ability to reset to higher arterial pressure during somatic afferent nerve stimulation is similar to that in the LZR.     

Baroreflex increases correlation and coherence of muscle sympathetic nerve activity (SNA) with renal and cardiac SNAs

Despite accumulating data of muscle sympathetic nerve activity (SNA) measured by human microneurography, whether neural discharges of muscle SNA correlates and coheres with those of other SNAs controlling visceral organs remains unclear. Further, how the baroreflex control of SNA affects the relations between these SNAs remains unknown. In urethane and alpha-chloralose anesthetized, vagotomized, and aortic-denervated rabbits, we recorded muscle SNA from the tibial nerve using microneurography and simultaneously recorded renal and cardiac SNAs. After isolating the carotid sinuses, we produced a baroreflex closed-loop condition by matching the isolated intracarotid sinus pressure (CSP) with systemic arterial pressure (CLOSE). We also fixed CSP at operating pressure (FIX) or altered CSP widely (WIDE: operating pressure +/- 40 mmHg). Under these conditions, we calculated time-domain and frequency-domain measures of the correlation between muscle SNA and renal or cardiac SNAs. At CLOSE, muscle SNA resampled at 1 Hz correlated with both renal (r(2) = 0.71 +/- 0.04, delay = 0.10 +/- 0.004 s) and cardiac SNAs (r(2) = 0.58 +/- 0.03, delay = 0.13 +/- 0.004 s) at optimal delays. Moreover,muscle SNA at CLOSE strongly cohered with renal and cardiac SNAs(coherence >0.8) at the autospectral peak frequencies, and weakly (0.4-0.5) at the remaining frequencies. Increasing the magnitude of CSP change from FIX to CLOSE and further to WIDE resulted in corresponding increases in correlation and coherence functions at nonpeak frequencies, and the coherence functions at peak frequencies remained high (>0.8). In conclusion, muscle SNA correlates and coheres approximately with renal and cardiac SNAs under closed-loop baroreflex conditions. The arterial baroreflex is capable of potently homogenizing neural discharges of these SNAs by modulating SNA at the nonpeak frequencies of SNA autospectra.     

Partial blockade of skeletal muscle somatosensory afferents attenuates baroreflex resetting during exercise in humans

During exercise, the carotid baroreflex is reset to operate around the higher arterial pressures evoked by physical exertion. The purpose of this investigation was to evaluate the contribution of somatosensory input from the exercise pressor reflex to this resetting during exercise. Nine subjects performed seven minutes of dynamic cycling at 30 % of maximal work load and three minutes of static one-legged contraction at 25 % maximal voluntary contraction before (control) and after partial blockade of skeletal muscle afferents with epidural anaesthesia. Carotid baroreflex function was assessed by applying rapid pulses of hyper- and hypotensive stimuli to the neck via a customised collar. Using a logistic model, heart rate (HR) and mean arterial pressure (MAP) responses to carotid sinus stimulation were used to develop reflex function stimulus-response curves. Compared with rest, control dynamic and static exercise reset carotid baroreflex-HR and carotid baroreflex-MAP curves vertically upward on the response arm and laterally rightward to higher operating pressures. Inhibition of exercise pressor reflex input by epidural anaesthesia attenuated the bi-directional resetting of the carotid baroreflex-MAP curve during both exercise protocols. In contrast, the effect of epidural anaesthesia on the resetting of the carotid baroreflex-HR curve was negligible during dynamic cycling whereas it relocated the curve in a laterally leftward direction during static contraction. The data suggest that afferent input from skeletal muscle is requisite for the complete resetting of the carotid baroreflex during exercise. However, this neural input appears to modify baroreflex control of blood pressure to a greater extent than heart rate.     

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.     

Static and dynamic changes in carotid artery diameter in humans during and after strenuous exercise

Arterial baroreflex function is altered by dynamic exercise, but it is not clear to what extent baroreflex changes are due to altered transduction of pressure into deformation of the barosensory vessel wall. In this study we measured changes in mean common carotid artery diameter and the pulsatile pressure: diameter ratio (PDR) during and after dynamic exercise. Ten young, healthy subjects performed a graded exercise protocol to exhaustion on a bicycle ergometer. Carotid dimensions were measured with an ultrasound wall-tracking system; central arterial pressure was measured with the use of radial tonometry and the generalized transfer function; baroreflex sensitivity (BRS) was assessed in the post-exercise period by spectral analysis and the sequence method. Data are given as means ± s.e.m . Mean carotid artery diameter increased during exercise as compared with control levels, but carotid distension amplitude did not change. PDR was reduced from 27.3 ± 2.7 to 13.7 ± 1.0 μm mmHg⁻¹. Immediately after stopping exercise, the carotid artery constricted and PDR remained reduced. At 60 min post-exercise, the carotid artery dilated and the PDR increased above control levels (33.9 ± 1.4 μm mmHg⁻¹). The post-exercise changes in PDR were closely paralleled by those in BRS (0.74 ≤ r ≤ 0.83, P < 0.05). These changes in mean carotid diameter and PDR suggest that the mean baroreceptor activity level increases during exercise, with reduced dynamic sensitivity; at the end of exercise baroreceptors are suddenly unloaded, then at 1 h post-exercise, baroreceptor activity increases again with increasing dynamic sensitivity. The close correlation between PDR and BRS observed at post-exercise underlies the significance of mechanical factors in arterial baroreflex control.