Effects of calcium channel blockers on isolated carotid baroreceptors and baroreflex

Our study determined the effects of the calcium antagonists, nifedipine and verapamil, on the carotid sinus baroreceptors and baroreflex. The left carotid sinus region in dogs was vascularly isolated and filled with oxygenated physiological salt solution. Steady-state multiunit activity was recorded from the carotid sinus nerve for sinus pressures of 50-200 mmHg after bathing the carotid sinus region in a solution containing no drug, 10 micrograms/ml nifedipine (n = 6), or 5 micrograms/ml verapamil (n = 5). The slopes of the curves relating carotid sinus nerve activity (% of maximum control) to carotid sinus pressure were control, 0.81 +/- 0.06; nifedipine, 1.29 +/- 0.14; and verapamil, 0.48 +/- 0.06%/mmHg, indicating that nifedipine increased and verapamil decreased the sensitivity of the carotid sinus baroreceptors. Additional studies with bilateral carotid sinus isolation (carotid sinus nerves intact) indicated that nifedipine enhanced and verapamil attenuated carotid baroreflex control of renal sympathetic nerve activity. Pressure-volume curves generated in the isolated carotid sinus showed that effects on smooth muscle do not account for the opposing effects of the two Ca2+ antagonists. Omitting Ca2+ from the physiological solution resulted in increased carotid sinus nerve activity, an effect blocked by verapamil but not nifedipine. Verapamil, but not nifedipine, inhibited veratrine-induced (Na+-dependent) excitation of carotid baroreceptors. Thus the excitatory effects of nifedipine on the carotid sinus baroreceptors are dependent on Ca2+ mechanisms, whereas the inhibitory effects of verapamil may be due mainly to interference with the inward Na+ current.     

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.     

Lack of interaction between adenosine-induced vasodilatation and carotid baroreflex-induced changes in sympathetic activity in dog hindlimb artery

In anaesthetized dogs, a hindlimb was vascularly isolated and perfused at a constant flow rate of 7.7 +/- 1.9 ml min-1 100 g-1 (mean +/- S.E.M.; n = 5) through the femoral artery. The carotid sinuses were isolated and perfused at high (greater than 145 mmHg) or low (less than 75 mmHg) pressure to enable reflex sympathetic tone on the hindlimb vessels to be controlled. Both vagi were sectioned in the neck and mean aortic blood pressure was held constant by connection of the aorta to a reservoir. The responses to infusion of three doses of adenosine at high and low carotid sinus pressures were not significantly different: infusion of 0.60 +/- 0.16 microM-adenosine reduced femoral arterial perfusion pressure (FAPP) by 11.6 +/- 3.2% (n = 6) at high carotid sinus pressure and by 12.6 +/- 5.1% (n = 4) at low carotid sinus pressure, while 4.71 +/- 0.49 microM-adenosine reduced FAPP by 20.8 +/- 4.8% (n = 6) at high carotid sinus pressure and by 20.7 +/- 4.8% (n = 6) at low carotid sinus pressure; 50.1 +/- 7.3 microM-adenosine reduced FAPP by 36.7 +/- 5.5% (n = 6) at high carotid sinus pressure and by 27.7 +/- 7.8% (n = 5) at low carotid sinus pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rabbit cardiovascular responses to aortic nerve stimulation at fixed carotid pressure.

In pentobarbital-anesthetized rabbits with aortic nerves cut, reflex heart rate and mean arterial pressure (MAP) changes were quantified in response to maximal central stimulation of the left aortic nerve (LANS) before and during steady-state changes in isolated carotid intrasinus pressure (ISP). To distinguish possible vagally mediated cardiopulmonary influences, responses were measured before and after vagotomy. Changes in MAP observed by altering ISP within +/- 15 mmHg of the equilibrium pressure (EP) were linear and inversely correlated to changes in ISP, with a slope of approximately 3 both before and after vagotomy (r greater than or equal to 0.929, P less than 0.05). The peak fall in MAP during LANS was dependent upon ISP. The change in the MAP responses to LANS for each mmHg change in ISP ranged from 1.7 with vagi intact to 1.3 after vagotomy. Heart rate was unaltered by isolation of the carotid sinus and was independent of the small changes in ISP between +/- 15 mmHg of EP. These results indicate that blood pressure changes elicited by the aortic baroreflex are extremely sensitive to the degree of carotid sinus compensation. Thus, to assess the sensitivity of any arterial reflex area, the existing level of compensation by other barosensitive areas must be known.     

Baroreflex inhibition of the human sinus node: importance of stimulus intensity, duration, and rate of pressure change.

1. Carotid baroreceptors were stimulated with electronically controlled neck suction in five healthy young men and pulse interval prolongation was measured. Timing of the onset of stimuli in relation to cardiac activity was held constant, and stimulus intensity, duration, and dP/dt were varied independently. 2. In the subjects studied, sinus node responses to neck suction were proportional to dP/dt. However, variations of stimulus dP/dt within or above the normal range for arterial dP/dt did not influence the magnitude of integrated baroreflex responses, or the earliest portion of baroreflex sinus node inhibition. 3. Carotid baroreflex responses were linear over a wide range which extended beyond the normal range for human systolic arterial pressures. 4. Saturation of the carotid baroreceptor-cardiac reflex occurred at distending pressures of about 160 mmHg. 5. The average baroreflex responses of the group studied were highly reproducible over time. 6. Baroreflex gain correlated very strongly with base line pulse interval. 7. The magnitude of baroreflex responses increased linearly with the duration of carotid sinus distension and reached a maximum level with stimuli lasting 0-5 sec or more. 8. The results demonstrate that carotid sinus transfer characteristics can be measured in normal man, and that human response patterns are strikingly similar to those observed earlier in experimental animals.     

Effects of diazepam on the carotid sinus baroreflex control of circulation in rabbits

To examine the effects of diazepam on the carotid sinus baroreflex control of circulation, bilateral carotid occlusion was performed on 14 conscious rabbits with aortic denervation. The responses of mean arterial pressure, heart rate, cardiac output and total peripheral resistance were obtained. The haemodynamic responses to carotid occlusion were evaluated at cumulative doses of 0.5 and 1.0 mg kg-1 of diazepam. The administration of diazepam decreased cardiac output and increased total peripheral resistance significantly, but did not affect the arterial pressure and heart rate. The response of total peripheral resistance to carotid occlusion was significantly increased from 0.118 +/- 0.018 (mean +/- SE) to 0.154 +/- 0.026 mmHg min ml-1 at 1.0 mg kg-1 of diazepam. The heart rate response was attenuated significantly from 41 +/- 5 to 24 +/- 4 beats min-1 at 1.0 mg kg-1 of diazepam. Diazepam did not alter the response of arterial pressure to carotid occlusion. We suggest that the dissociated effects of diazepam on the reflex control of circulation reflect the dissociated influences of diazepam on the central sympathetic and vagal-mediated pathways.     

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)     

Characteristics of the carotid baroreflex in man during normal and flow-restricted exercise.

Eight subjects were studied in the supine position at rest, during normal dynamic leg exercise (control exercise) and with blood-flow restriction in the working legs (flow-restricted exercise). Graded muscle blood-flow restriction was accomplished by applying a supra-atmospheric pressure of 50 mmHg to the working legs. During incremental-load exercise, flow restriction reduced exercise performance and peak heart rate by 36% and 13%, respectively. The function of the cardiac branch of the carotid baroreflex was studied over its full operational range, at rest and during constant-load control and flow-restricted exercise, by measuring R-R intervals during application of pulse-synchronous graded pressures (40 to -65 mmHg) in a neck-chamber device. Heart rate and arterial pressure were higher during flow-restricted than control exercise, indicating that the flow restriction activated the muscle chemoreflex. Raising the carotid transmural pressure (systolic arterial pressure minus neck-chamber pressure) was accompanied by increasing R-R intervals in all conditions. The set point (point of baseline carotid transmural pressure and R-R interval) coincided with the midportion of the pressure-response curve at rest and with the threshold point of the curve during exercise. The maximal rate of change in relative R-R intervals and the corresponding carotid transmural pressure range were higher during control exercise than at rest and highest during flow-restricted exercise, indicating that exercise and especially flow-restricted exercise increased carotid baroflex sensitivity, and shifted the carotid baroreflex optimal buffering range to higher pressures. The results suggest that the carotid baroflex attenuates exercise heart rate increases mediated by the muscle chemoreflex and/or by central command.     

Arterial blood pressure and carotid baroreflex function during arm and combined arm and leg exercise in humans

AIM: During arm cranking (A) blood pressure is higher than during combined arm and leg exercise (A + L), while the carotid baroreflex (CBR) is suggested to reset to control a higher blood pressure in direct relation to work intensity and the engaged muscle mass. METHOD: This study evaluated the function of the CBR by using neck pressure and neck suction during upright A, L and A + L in 12 subjects and, in order to evaluate a potential influence of the central blood volume on the CBR, also during supine A in five subjects. Exercise intensities for A and L were planned to elicit a heart rate response of c. 100 and 120 beats min(-1), respectively, in the upright position and both workloads were maintained during A + L and supine A. RESULTS: The CBR operating point, corresponding to the pre-stimulus blood pressure, was 88 +/- 6 mmHg (mean +/- SE) at rest. During upright A, L and A + L and supine A it increased to 109 +/- 9, 95 +/- 7, 103 +/- 7 and 104 +/- 4 mmHg, respectively, and it was thus higher during upright A than during A + L and supine A (P < 0.05). In addition, the CBR threshold and saturation pressures, corresponding to the minimum and maximum carotid sinus pressure, respectively, were higher during upright A than during supine A, A + L, L and at rest (P < 0.05) with no significant change in the maximal reflex gain. CONCLUSION: These findings demonstrate that during combined arm and leg and exercise in the upright position the CBR resets to a lower blood pressure than during arm cranking likely because the central blood volume is enhanced by the muscle pump of the legs.     

Carotid baroreflex regulation of vascular resistance in high-altitude Andean natives with and without chronic mountain sickness

We investigated carotid baroreflex control of vascular resistance in two groups of high-altitude natives: healthy subjects (HA) and a group with chronic mountain sickness (CMS), a maladaptation condition characterized by high haematocrit values and symptoms attributable to chronic hypoxia. Eleven HA controls and 11 CMS patients underwent baroreflex testing, using the neck collar method in which the pressure distending the carotid baroreceptors was changed by applying pressures of -40 to +60 mmHg to the chamber. Responses of forearm vascular resistance were assessed from changes in the quotient of blood pressure divided by brachial artery blood velocity. Stimulus-response curves were defined at high altitude (4338 m) and within 1 day of descent to sea level. We applied a sigmoid function or third-order polynomial to the curves and determined the maximal slope (equivalent to peak gain) and the corresponding carotid pressure (equivalent to 'set point'). The results showed that the peak gains of the reflex were similar in both groups and at both locations. The 'set point' of the reflex, however, was significantly higher in the CMS patients compared to HA controls, indicating that the reflex operates over higher pressures in the patients (94.4 +/- 3.0 versus 79.6 +/- 4.1 mmHg; P < 0.01). This, however, was seen only when subjects were studied at altitude; after descent to sea level the curve reset to a lower pressure with no significant difference between HA and CMS subjects. These results indicate that carotid baroreceptor control of vascular resistance may be abnormal in CMS patients but that descent to sea level rapidly normalizes it. We speculate that this may be explained by CMS patients having greater vasoconstrictor activity at altitude owing to greater hypoxic stimulation of chemoreceptors.     

Carotid baroreceptor reflexes in humans during orthostatic stress

Orthostatic stress, including standing, head-up tilting and lower body suction, results in increases in peripheral vascular resistance but little or no change in mean arterial pressure. This study was undertaken to determine whether the sensitivity of the carotid baroreceptor reflex was enhanced during conditions of decreased venous return. We studied eight healthy subjects and determined responses of pulse interval (ECG) and forearm vascular resistance (mean finger blood pressure divided by Doppler estimate of brachial artery blood velocity) to graded increases and decreases in carotid transmural pressure, effected by a neck suction/pressure device. Responses were determined with and without the application of lower body negative pressure (LBNP) at -40 mmHg. Stimulus-response curves were determined as the responses to graded neck pressure changes and the differential of this provided estimates of reflex sensitivity. Changes in carotid transmural pressure caused graded changes in R-R interval and vascular resistance. The cardiac responses were unaffected by LBNP. Vascular resistance responses, however, were significantly enhanced during LBNP and the peak gain of the reflex was increased from 1.2 +/- 0.3 (mean +/- S.E.M.) to 2.2 +/- 0.3 units (P < 0.05). The increased baroreflex gain may contribute to maintenance of blood pressure during orthostatic stress and limit the pressure decreases during prolonged periods of such stress.     

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.     

Characteristics of the carotid baroreflex in man during normal and flow-restricted exercise

EIKEN, O., CONVERTINO, V. A., DOERR, D. F., DUDLEY, G. A., MORARIU, G. & Mekjavic; I. B. 1992. Characteristics of the carotid baroreflex in man during normal and flow-restricted exercise. Acta Physiol Scand 144 , 325–331. Received 27 May 1 991 , accepted 29 October 1991. ISSN 0001–6772. School of Kinesiology, Simon Fraser University, Burnaby, B.C., Canada. Eight subjects were studied in the supine position at rest, during normal dynamic leg exercise (control exercise) and with blood-flow restriction in the working legs (flow-restricted exercise). Graded muscle blood-flow restriction was accomplished by applying a supra-atmospheric pressure of 50 mmHg to the working legs. During incremental-load exercise, flow restriction reduced exercise performance and peak heart rate by 36% and 13%, respectively. The function of the cardiac branch of the carotid baroreflex was studied over its full operational range, at rest and during constant-load control and flow-restricted exercise, by measuring R-R intervals during application of pulse-synchronous graded pressures (40 to -65 mmHg) in a neck-chamber device. Heart rate and arterial pressure were higher during flow-restricted than control exercise, indicating that the flow restriction activated the muscle chemoreflex. Raising the carotid transmural pressure (systolic arterial pressure minus neck-chamber pressure) was accompanied by increasing R-R intervals in all conditions. The set point (point of baseline carotid transmural pressure and R-R interval) coincided with the midportion of the pressure-response curve at rest and with the threshold point of the curve during exercise. The maximal rate of change in relative R-R intervals and the corresponding carotid transmural pressure range were higher during control exercise than at rest and highest during flow-restricted exercise, indicating that exercise and especially flow-restricted exercise increased carotid baroflex sensitivity, and shifted the carotid baroreflex optimal buffering range to higher pressures. The results suggest that the carotid baroflex attenuates exercise heart rate increases mediated by the muscle chemoreflex and/or by central command.     

Carotid-sinus baroreflex modulation of core and skin temperatures in rats: an open-loop approach

The neural mechanisms of the thermoregulatory control of core and skin temperatures in response to heat and cold stresses have been well clarified. However, it has been unclear whether baroreceptor reflexes are involved in the control of core and skin temperatures. To investigate how the arterial baroreceptor reflex modulates the body temperatures, we examined the effect of pressure changes of carotid sinus baroreceptors on core and skin temperatures in halothane-anesthetized rats. To open the baroreflex loop and control arterial baroreceptor pressure (BRP), we cut vagal and aortic depressor nerves and isolated carotid sinuses. We sequentially altered BRP in 20-mmHg increments from 60 to 180 mmHg and then in 20-mmHg decrements from 180 to 60 mmHg while measuring systemic arterial pressure (SAP), heart rate (HR), and core blood temperature (T(core)) at the aortic arch and skin temperature (T(skin)) at the tail. In response to the incremental change in BRP by 120 mmHg, SAP, HR, and T(core) fell by 90.3 +/- 5.1 mmHg, 60.3 +/- 10.5 beats min(-1), and 0.18 +/- 0.01 degrees C, respectively. T(skin) rose by 0.84 +/- 0.10 degrees C. The maximum rate of change per unit BRP change was -2.1 +/- 0.2 for SAP, -1.5 +/- 0.4 beats min(-1) mmHg(-1) for HR, -0.003 +/- 0.001 degrees C mmHg(-1) for T(core), and 0.011 +/- 0.002 degrees C mmHg(-1) for T(skin). After the administration of hexamethonium or bretylium, these baroreflexogenic responses were completely abolished. We concluded that T(core) and T(skin) are modulated by the arterial baroreceptor reflex.     

Effects of blood-volume distribution on the characteristics of the carotid baroreflex in humans at rest and during exercise

Seven supine subjects were studied at rest and during mild to moderate dynamic leg exercise with and without unloading of the cardiopulmonary baroreceptors accomplished by exposing the lower portion of the body to a subatmospheric pressure of 20 mmHg (Lower Body Negative Pressure, LBNP). The function of the cardiac branch of the carotid baroreflex was studied over its full operational range by measuring R-R intervals during application of pulse synchronous graded pressures (40 to – 65 mmHg) in a neck-chamber device. Raising the carotid transmural pressure (systolic arterial pressure minus neck-chamber pressure) induced increasing R-R intervals in all conditions. In conformity with previous results from our laboratories it was found that the maximal rate of change in relative R-R intervals and the corresponding transmural pressure were higher during exercise than at rest, indicating that exercise increased the carotid baroreflex sensitivity and shifted its optimal buffering range to higher arterial pressures. LBNP did not affect the characteristics of the reflex at rest nor during exercise. It is concluded that reduced central venous pressure with consequent selective cardiopulmonary receptor disengagement exerts no influence on the carotid baroreflex control of heart rate (HR), as tested over the entire arterial pressure-effector response relation, either at rest or during mild-moderate exercise.     

Carotid-cardiac baroreflex function does not influence blood pressure regulation during head-up tilt in humans

The influence of the carotid-cardiac baroreflex on blood pressure regulation was evaluated during supine rest and 40 degrees head-up tilt (HUT) in 9 healthy young subjects with and without full cardiac vagal blockade. The carotid baroreflex responsiveness, or maximal gain (G(MAX)), was assessed from the beat-to-beat changes in heart rate (HR) and mean arterial pressure (MAP) by the variable neck pressure and suction technique ranging in pressure from +40 to -80 Torr, with and without glycopyrrolate (12.0 +/- 1.0 microg/kg body weight; mean +/- SE). In the supine position, glycopyrrolate increased the HR to 91 +/- 3 bpm, from 54 +/- 3; MAP to 89 +/- 2 mmHg, from 76 +/- 2; and cardiac output to 6.8 +/- 0.3 l.min(-1), from 4.9 +/- 0.3 (P < 0.05). The G(MAX) of the carotid baroreflex control of HR was reduced to -0.06 +/- 0.01 bpm.mmHg(-1), from -0.30 +/- 0.02 (P < 0.05) with no significant effect on the G(MAX) of the carotid baroreflex control of MAP. During HUT the carotid baroreflex control of MAP was unchanged, though the G(MAX) of the carotid baroreflex control of HR was increased (P < 0.05). During HUT, central blood volume, assessed by electrical thoracic admittance, and total vascular conductance were decreased with and without glycopyrrolate. Furthermore, glycopyrrolate reduced G(MAX) of the carotid baroreflex control of HR during HUT (P < 0.05) with no significant effect on G(MAX) of the carotid baroreflex control of MAP. These data suggest that during supine rest and HUT-induced decreases in central blood volume, the carotid baroreflex control of HR is mediated primarily via parasympathetic activity. Furthermore, the maintenance of arterial blood pressure during postural stress is primarily mediated by arterial and cardiopulmonary reflex regulation of sympathetic activity and its effects on the systemic vasculature.     

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.     

Effect of cervical sympathetic nerve stimulation on canine carotid sinus reflex.

In the chloralose-anesthetized dog the carotid sinus on one side of the neck was isolated vascularly. Pressure in the isolated sinus [carotid sinus pressure (CSP)], electrocardiogram, and systemic arterial pressure were recorded. Both vagosympathetic trunks were cut and the contralateral common carotid artery was occluded or the contralateral sinus nerve was cut to reduce reflex buffering of arterial pressure changes. By varying CSP from 50 to 250 mmHg the full range of the reflex response was examined. Electrical stimulation of the peripheral end of the cut ipsilateral cervical sympathetic nerve brought about a rapid decrease in mean arterial pressure (MAP) and heart rate (HR) at lower CSPs, no change in these variables at midrange CSPs, and a gradual increase at higher CSPs, such that the gain of the reflex was reduced (1.89 +/- 0.19 to 1.33 +/- 0.15 mmHg/mmHg). The decrease in MAP and HR at lower CSPs implies an increase in baroreceptor activity whereas the converse would appear to occur at higher CSPs. These responses attained a maximum value at low stimulus frequencies (less than 10 Hz).     

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.     

Reflex responses from the main pulmonary artery and bifurcation in anaesthetised dogs

This study was undertaken to determine the reflex cardiovascular and respiratory responses to discrete stimulation of pulmonary arterial baroreceptors using a preparation in which secondary modulation of responses from other reflexes was prevented. Dogs were anaesthetised with -chloralose, artificially ventilated, the chests widely opened and a cardiopulmonary bypass established. The main pulmonary arterial trunk, bifurcation and extrapulmonary arteries as far as the first lobar arteries on each side were vascularly isolated and perfused through the left pulmonary artery and drained via the right artery through a Starling resistance which controlled pulmonary arterial pressure. Pressures distending systemic baroreceptors and reflexogenic regions in the heart were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a vascularly isolated hind limb and to the remainder of the subdiaphragmatic systemic circulation, both of which were perfused at constant flows. Respiratory responses were assessed from recordings of efferent phrenic nerve activity. Increases in pulmonary arterial pressure consistently evoked increases in both perfusion pressures and in phrenic nerve activity. Both vascular and respiratory responses were obtained when pulmonary arterial pressure was increased to above about 30 mmHg. Responses increased at higher levels of pulmonary arterial pressures. In 13 dogs increases in pulmonary arterial pressure to 45 mmHg increased systemic perfusion pressure by 24 +/- 7 mmHg (mean +/- S.E.M.) from 162 +/- 11 mmHg. Setting carotid sinus pressure at different levels did not influence the vascular response to changes in pulmonary arterial pressure. The presence of a negative intrathoracic pressure of -20 mmHg resulted in larger vascular responses being obtained at lower levels of pulmonary arterial pressure. This indicates that the reflex may be more effective in the intact closed-chest animal. These results demonstrate that stimulation of pulmonary arterial baroreceptors evokes a pressor reflex and augments respiratory drive. This reflex is likely to be elicited in circumstances where pulmonary arterial pressure increases and the negative excursions of intrathoracic pressure become greater. They are likely, therefore, to be involved in the cardio-respiratory response to exercise as well as in pathological states such as pulmonary hypertension or restrictive or obstructive lung disease.