Increases In Carotid Sinus Pressure Research Articles

Reflexes from pulmonary arterial baroreceptors in dogs: interaction with carotid sinus baroreceptors

In contrast to the reflex vasodilatation occurring in response to stimulation of baroreceptors in the aortic arch, carotid sinuses and coronary arteries, stimulation of receptors in the wall of pulmonary arteries results in reflex systemic vasoconstriction. It is rare for interventions to activate only one reflexogenic region, therefore we investigated how these two types of reflexes interact. In anaesthetized dogs connected to cardiopulmonary bypass, reflexogenic areas of the carotid sinuses, aortic arch and coronary arteries and the pulmonary artery were subjected to independently controlled pressures. Systemic perfusion pressure (SPP) measured in the descending aorta (constant flow) provided an index of systemic vascular resistance. In other experiments, sympathetic efferent neural activity was recorded in fibres dissected from the renal nerve (RSNA). Physiological increases in pulmonary arterial pressure (PAP) induced significant increases in SPP (+39.1 ± 10.4 mmHg) and RSNA (+17.6 ± 2.2 impulses s(−1)) whereas increases in carotid sinus pressure (CSP) induced significant decreases in SPP (−42.6 ± 10.8 mmHg) and RSNA (−42.8 ± 18.2 impulses s(−1)) (P < 0.05 for each comparison; paired t test). To examine possible interactions, PAP was changed at different levels of CSP in both studies. With CSP controlled at 124 ± 2 mmHg, the threshold, 'set point' and saturation pressures of the PAP–SPP relationship were higher than those with CSP at 60 ± 1 mmHg; this rightward shift was associated with a significant decrease in the reflex gain. Similarly, increasing CSP produced a rightward shift of the PAP–RSNA relationship, although the effect on reflex gain was inconsistent. Furthermore, the responses to changes in CSP were influenced by setting PAP at different levels; increasing the level of PAP from 5 ± 1 to 33 ± 3 mmHg significantly increased the set point and threshold pressures of the CSP–SPP relationship; the reflex gain was not affected. These results indicate the existence of interaction between pulmonary arterial and carotid sinus baroreceptor reflexes; physiological and pathological states that alter the stimulus to one may alter the reflex responses from the other.

Reflex control of splanchnic blood volume in anaesthetized dogs.

1. In chloralose-anaesthetized, artificially ventilated dogs, the splenic pedicle was tied and the carotid sinuses were vascularly isolated and perfused at controlled pressures. In Series 1 experiments, the hepatosplanchnic circulation was perfused through the abdominal aorta with a tie on the aorta separating it from the caudal circulation, which was perfused through the femoral arteries. The two circulations were drained from cannulae in the inferior vena cava and the femoral veins, with a tie on the inferior vena cava separating the two. In Series 2, the splanchnic circulation drained from the portal vein. In both series, inflows and outflows were measured and integrated to derive volume changes. Capacitance responses were assessed during constant flow, and capacitance plus passive responses were obtained during constant pressure perfusion. 2. In Series 1, an increase in carotid sinus pressure (from 8 to 26 kPa) during constant flow and constant pressure perfusion increased hepatosplanchnic volume by 2.5 and 5.7 ml (kg body weight)-1, respectively. The volume of the subdiaphragmatic circulation did not increase during constant flow, but during constant pressure it increased by 2.0 ml (kg body weight)-1. 3. In Series 2, increasing carotid pressure during constant flow and constant pressure increased the volume of the splanchnic circulation by 0.5 and 4.2 ml (kg body weight)-1, respectively. 4. These results confirm that carotid baroreceptor stimulation causes larger volume changes during constant pressure perfusion than during constant flow perfusion. Also, the active capacitance change in the splanchnic circulation is small in relation to the passive response. We propose that in dogs (following splenic ligation), the major active capacitance control is from the liver. However, large passive changes in splanchnic volume occur due to changes in flow.

Role of endogenous nitric oxide in the brain stem on the rapid adaptation of baroreflex.

It has been shown that nitric oxide in the brain stem plays an important role in the control of sympathetic nerve activity. We examined the role of endogenous nitric oxide in the brain stem in the rapid central adaptation of baroreflex control of sympathetic nerve activity in anesthetized rabbits. Bilateral carotid sinuses were isolated, and a stepwise increase in pressure of 25 or 50 mm Hg for 50 to 60 seconds was applied to the carotid sinuses while the arterial pressure and renal sympathetic nerve activity were recorded. The renal sympathetic nerve activity was inhibited by the stepwise increase in carotid sinus pressure, but thereafter it gradually returned toward the baseline level despite the fact that carotid sinus pressure was kept constant. This procedure was performed after intracisternal injection of N(omega)-nitro-L-arginine methyl ester (L-NAME, 8 micromol), N(omega)-nitro-D-arginine methyl ester (D-NAME, 8 micromol), L-arginine (40 micromol), or the vehicle solution. The magnitude of the immediate and maximal inhibition of renal sympathetic nerve activity caused by a stepwise increase in carotid sinus pressure was similar between the vehicle and L-NAME treatment, but the rate of recovery of the renal sympathetic nerve activity after immediate inhibition was faster after L-NAME than after vehicle. L-Arginine reversed the effects of L-NAME. However, D-NAME or L-arginine alone had no such effects on the rate of recovery of the nerve activity. These results thus suggest that endogenous nitric oxide in the brain stem attenuates rapid adaptation of the arterial baroreflex control of the sympathetic nerve activity in rabbits.

The effects of propofol, methohexitone and isoflurane on the baroreceptor reflex in the cat.

The effects of propofol (P), methohexitone (M) and isoflurane (I) on the baroreceptor reflex were studied in a cat model in which the blood pressure in a bilateral isolated carotid sinus preparation was artificially varied between 50-200 mmHg. The influence from aortic and cardiopulmonary baroreceptors was excluded by vagotomy. With basal chloralose anaesthesia as control, the investigated anaesthetics were used in doses corresponding to MAC 0.5 and 1.0. The maximum change in systemic mean arterial pressure (MAP) and heart rate (HR) following a defined increase in carotid sinus pressure was used as an index of baroreceptor reflex sensitivity. Compared to control, M and I anaesthesia were associated with significant depression of baroreceptor reflex sensitivity at the high dose (corresponding to MAC 1.0), and during I anaesthesia also at the low dose (MAC 0.5). The baroreceptor reflex sensitivity was maintained during propofol anaesthesia. The carotid sinus pressure interval at which the maximum changes in MAP could be elicited, was significantly higher during M than during P. This indicates resetting of the baroreflex.

Effects of epinephrine on firing characteristics of two functionally different types of carotid baroreceptors.

Sympathetic stimulation and catecholamine exposure have been shown to sensitize the arterial baroreceptors, but the extent or importance of this effect is not known. We performed this study to investigate the effects of sympathetic feedback on the carotid sinus baroreceptors, specifically examining the effect of the stimulation on the two different functional types of baroreceptors characterized in an earlier study. The existence of two baroreceptor function-response curves has suggested that the roles of the two functionally different baroreceptors may not be the same. If true, the effects of epinephrine exposure on baroreceptor firing characteristics may contribute to differential roles played by each baroreceptor type in the control of blood pressure. Single-fiber baroreceptor activity from a vascularly isolated carotid sinus was recorded during slow increases in carotid sinus pressure before and during exposure to epinephrine (10(-8) to 10(-6) M). Baroreceptor firing characteristics were determined from function curves plotting carotid sinus pressure versus nerve activity, with curve-fitting analysis of the hyperbolic type I and sigmoidal type II baroreceptor curves used to obtain threshold (Pth) and saturation (Psat) pressures, threshold (Fth) and saturation (Fsat) firing rates, and sensitivity (slope) for each baroreceptor before and during epinephrine exposure. The possible mechanisms of observed changes were examined using our previously published baroreceptor computer model. Epinephrine exposure was found to significantly increase sensitivity, Fth, and Fsat of both types of baroreceptors, with a relatively greater effect on type I sensitivity and on type II Fth and Fsat. Epinephrine also was found to increase the level of spontaneous discharge for type II baroreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid sinus baroreceptor sensitivity in experimental heart failure.

Single-unit carotid sinus baroreceptor activity was recorded in normal and heart-failure (pacing-induced) dogs. The sensitivity of these units was compared between the two groups of dogs. After development of clinical heart failure, the animals were anesthetized, and the left carotid sinus was vascularly isolated and perfused with oxygenated Krebs-Henseleit solution. Single-unit baroreceptor discharge was recorded from the carotid sinus nerve in response to stepwise increases in carotid sinus pressure (CSP). In addition, the carotid sinus diameter was measured with sonomicrometer crystals. In this way, both CSP-discharge and CSP-diameter curves were constructed for both normal and heart-failure dogs. Analysis of these curves demonstrated that the heart-failure group exhibited a significant decrease in peak discharge (48.1 +/- 3.0 vs. 22.2 +/- 2.2 spikes/sec; p less than 0.001) and a significant elevation in threshold pressure compared with the normal animals (91.0 +/- 5.0 vs. 119.1 +/- 4.4 mm Hg; p less than 0.001). The peak slope of the CSP-discharge curve was also significantly lower in the heart-failure group (0.63 +/- 0.06 vs. 0.40 +/- 0.09 spikes/sec/mm Hg; p less than 0.05). In the heart-failure group, perfusion of the carotid sinus with ouabain (0.01 micrograms/ml) caused a significant decrease in threshold pressure and a significant increase in peak discharge frequency, as well as an increase in slope of the CSP-discharge curve. There were no changes in CSP-diameter relations in response to ouabain. This dose of ouabain had no effect on pressure-discharge relations or carotid sinus diameters in normal dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostaglandins in carotid sinus enhance baroreflex in rabbits

The purpose of this study was to examine the possible influence of endogenous prostaglandins in the carotid sinus on the arterial baroreflex. Lumbar sympathetic nerve activity (LSNA) and arterial pressure were recorded during step increases in isolated carotid sinus pressure in rabbits anesthetized with chloralose. Baroreflex responses were facilitated after intrasinus administration of prostacyclin (PGI2; 5 and 10 microM, n = 6) or arachidonic acid (10 microM, n = 12). PGI2 (10 microM) increased the slope of the carotid sinus pressure-LSNA relation (gain) from -0.32 +/- 0.09 to -1.19 +/- 0.38 spikes.s-1.mmHg-1 and decreased the pressure at which 50% of the maximum inhibition of LSNA occurred (EP50) from 127 +/- 5 to 98 +/- 4 mmHg (P less than 0.05). Similar responses were observed with arachidonic acid. Baroreflex responses were attenuated after intrasinus administration of indomethacin (40 and 80 microM, n = 5) or aspirin (1 and 2 mM, n = 7). Indomethacin (80 microM) decreased the gain of the baroreflex from -1.02 +/- 0.24 to -0.47 +/- 0.16 spikes.s-1.mmHg-1 and increased the EP50 from 121 +/- 6 to 133 +/- 7 mmHg (P less than 0.05). Both indomethacin (80 microM) and aspirin (2 mM) reduced the maximum percent inhibition of LSNA significantly. The results indicate that prostaglandins within the carotid sinus facilitate the baroreflex control of LSNA. The attenuation of the baroreflex after inhibition of cyclooxygenase suggests that endogenous prostaglandins contribute to the activation of baroreceptors during increases in carotid sinus pressure.

A central mechanism of acute baroreflex resetting in the conscious dog.

The role of the central nervous system in the mechanism(s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the left carotid sinus pressure (LCcsp) at a given value for 20 minutes using a pulsatile pressure control system while at the same time keeping the right carotid sinus pressure (RCSP) at a subthreshold level (approximately 40 mm Hg). At the end of the 20 minutes, the LCcsp) was reduced to approximately 20 mm Hg, and a baroreflex (RCSP-mean arterial pressure [MAP]) curve was generated on the right carotid sinus using static-step increases in carotid sinus pressure. At the control LCcsp of 100 mm Hg, the RCSP-MAP baroreflex had a threshold pressure (Pth) of 86.6 +/- 3.1 mm Hg and a set point pressure (Psp) of 104.7 +/- 2.5 mm Hg. Increasing LCcsp) to 140 mm Hg for 20 minutes caused these parameters for the right carotid baroreflex to increase. Pth and Psp increased by 18.4 +/- 4.0 and 14.2 +/- 3.0 mm Hg, respectively (p less than 0.05). The baroreflex curve, therefore, was shifted upward and to the right. Decreasing LCcsp to 60 mm Hg caused Pth and Psp to decrease by 24.7 +/- 5.0 and 18.1 +/- 2 mm Hg, respectively (p less than 0.05). The baroreflex curve was therefore shift downward and to the left. The percent of resetting of Pth and Psp was 46 +/- 9% and 36 +/- 8%, respectively, when LCcsp was 140 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamic changes in venous outflow by baroreflex and left ventricular distension.

We examined the dynamic changes in venous outflow from the splanchnic and extrasplanchnic vascular beds in response to carotid sinus (CS) baroreflex and left ventricular (LV) distension in 12 dogs anesthetized with pentobarbital sodium. Splenic sympathetic nerve activity was measured in an additional group of six dogs. A heart-lung bypass was used with constant cardiac output and constant venous pressure. LV distension was produced by inflating a balloon in the LV. LV distension and an increase in CS pressure from 50 to 200 mmHg decreased blood pressure by 26 +/- 5 and 30 +/- 6 mmHg and increased vascular capacitance by 5.5 +/- 0.9 and 4.5 +/- 1.2 ml/kg, respectively. Splanchnic venous outflow exhibited a transient decrease, whereas extrasplanchnic venous outflow showed a transient increase, in response to LV distension and increasing CS pressure, accompanied by a sustained decrease in splenic nerve activity. The results indicate important differences between splanchnic and extrasplanchnic components of the total venous system in terms of the regulation of venous capacitance. It is suggested that changes in venous capacitance produced by LV distension and CS baroreflex are primarily due to active changes in splanchnic venous tone.

Effect of sympathetic sensitization of baroreceptors on renal nerve activity.

The role of sympathetic efferent innervation of the carotid sinus on the regulation of baroreceptor sensitivity was examined in thiopental-sodium anesthetized dogs (5 mg X kg-1 X h-1 infusion). Baroreflex sensitivity was defined as the slope of renal sympathetic efferent nerve activity vs. carotid sinus pressure in an isolated, perfused carotid sinus. Slopes were obtained before and after sinus sympathectomy performed by section of the cervical sympathetic trunk. There was no significant differences between baroreflex decreases in renal sympathetic activity due to increases in carotid sinus pressure before and after sympathectomy, but the responses to decreases in carotid sinus pressure after sympathectomy were significantly greater than control. Base-line level of renal sympathetic activity, obtained at a constant perfusion pressure of 115 mmHg, abruptly increased by 11% in response to sinus sympathectomy. The response of baroreceptors to sympathomimetic stimulation was examined by recording carotid baroreceptor afferent nerve activity during ramp changes in carotid sinus pressure after addition of epinephrine (10(-8) to 10(-6) M) to the perfusate of the sympathetically denervated sinus. The slopes of the sinus nerve activity vs. carotid sinus pressure were used as direct indexes of baroreceptor sensitivity. Lower levels of epinephrine (10(-8), 10(-7) M) increased the sensitivity of the baroreceptors and reduced renal nerve activity back toward presympathectomy levels. A higher dose of epinephrine (10(-6) M) did not significantly increase baroreceptor sensitivity. The results of this study suggest that sinus sympathetic fibers produce a tonic sensitization of the baroreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of distension of the urinary bladder on efferent cardiac sympathetic nerve fibres which respond to stimulation of atrial receptors.

The effect of distension of the urinary bladder on the activity in the efferent cardiac sympathetic nerves which responded to stimulation of atrial receptors or those which responded to stimulation of carotid baroreceptors or chemoreceptors, was studied in dogs anaesthetized with chloralose; the urinary bladder was distended with warm saline, small balloons were positioned at the right pulmonary vein-atrial junctions and distended with 1 cm3 saline, and the carotid sinuses were vascularly isolated and perfused with blood at constant flow. The efferent cardiac sympathetic nerve fibres which responded to stimulation of carotid baroreceptors and chemoreceptors by a decrease in activity always responded with an increase in activity in response to distension of the urinary bladder. In contrast, in those efferent cardiac sympathetic nerve fibres which did not respond to an increase in carotid sinus pressure, but responded to stimulation of atrial receptors by an increase in activity, distension of the urinary bladder neither caused a significant change in activity nor produced a reproducible pattern of response. It is concluded that the efferent cardiac sympathetic nerve fibres which respond to stimulation of atrial receptors are separate from those which respond to distension of the urinary bladder.

Static and dynamic responses of carotid sinus baroreceptors in dogs with chronic volume overload.

In this study we determined if there are any alterations in carotid sinus baroreceptor discharge in a model of heart failure in the dog. The left carotid sinus was isolated and perfused at 100 mmHg with a modified Krebs-Henseleit solution. Two groups of dogs were used: a normal group and a group with a chronic aorto-caval fistula (a.v.f.) of up to 20 weeks duration. The a.v.f. group had a significantly elevated heart rate and left ventricular end diastolic pressure as well as an increased arterial pulse pressure compared to normals. However, mean arterial pressure measured in the aortic arch was not significantly different. Carotid sinus pressure-discharge curves were constructed during increases in carotid sinus pressure by steps and by ramps of pressure change up to 200 mmHg/s. Carotid sinus diameter was also measured using sonomicrometer crystals. In six dogs from each group the sodium, potassium and water content of the right carotid sinus was measured. Several parameters of second order polynomial curves that were fitted to the data were compared between the two groups for step and ramp increases in pressure. These included maximum baroreceptor gain, threshold pressure and plateau pressure. Baroreceptor gain was significantly lower in the a.v.f. group for the step and lowest ramp rate pressure changes. Threshold pressure was significantly higher for the a.v.f. group for steps and the three slowest ramp rates. Plateau pressures were significantly higher for the steps and lowest ramp rate. The carotid sinus strain that was produced at any given carotid sinus pressure was not significantly different between the two groups. In addition, there was no difference in the sodium, potassium or water content of the carotid sinus between the two groups. It was concluded that there is a depression of the static discharge characteristics in this model of heart failure which is not due to an alteration in electrolyte or water content or to the compliance of the carotid sinus.

Carotid sinus baroreflex influence on electrophysiologic properties of the canine atrioventricular node and ventricle

This study examines the efferent mechanisms of carotid sinus baroreflex influence on ventricular repolarization and refractory period compared with effects on atrioventricular (AV) nodal conduction. Pressure was controlled in both carotid sinuses by the Moisejeff technique in 16 chloralose-anesthetized dogs. Increases in carotid sinus pressure during pacing produced graded prolongation of AV nodal conduction, ventricular repolarization and refractory period with a threshold at a carotid sinus pressure of 120 mm Hg and a peak response at 200 mm Hg. Atropine, 0.4 mg/kg, attenuated the peak percent change in ventricular repolarization interval by only 12 ± 14% (± standard error of the mean) despite a significantly greater attenuation (48 ± 11%, p <0.05) in peak percent change in AV nodal conduction. However, stellate ganglionectomy attenuated the peak percent change in ventricular repolarization (42 ± 19%), similar to effects on AV nodal conduction (59 ± 21%, p >0.25). Changes in mean arterial pressure, ventricular end-diastolic segment length or segment length shortening with systole (sonomicrometer technique) did not account for the electrophysiologic responses. Latency to peak effect on ventricular repolarization (43 ± 7 seconds) was slower than that on AV nodal conduction (23 ± 6 seconds, p <0.05). This difference in time course was not abolished by atropine. Thus, the carotid sinus baroreflex prolongs ventricular repolarization and refractoriness mainly by withdrawal of sympathetic influence; AV nodal conduction is prolonged by both vagal activation and sympathetic withdrawal. In addition, differences in time course between ventricular and AV nodal electrophysiologic responses are not explained by different efferent autonomic mechanisms.

Circulatory control in canine acrylamide neuropathy

The baroreflex regulation of arterial blood pressure and heart rate was examined in dogs with acrylamide-induced peripheral neuropathy. In anaesthetized animals the carotid sinuses were isolated from the systemic circulation and perfused. The carotid sinus and vagus nerves were kept intact. The maximum baroreflex gain (the ratio of the change in systemic pressure to a change in sinus pressure) was significantly greater in the treated animals. A step increase in carotid sinus pressure produced long periods of asystole and sustained bradycardia in the animals with neuropathy. The alterations in the baroreceptor reflex responses were consistent with dysfunction of baroreceptor fibres in the vagus.

Effects of clonidine on baroreceptor function in anesthetized dogs

The effects of clonidine (15–30 μg/kg i.v.) on carotid sinus and other baroreceptors were investigated in anesthetized dogs. In 14 control dogs, right carotid sinus pressure was controlled by retrograde perfusion through the common carotid artery at constant flow with femoral arterial blood. Graded reductions in heart rate and blood pressure induced by graded increases in carotid sinus pressure were prevented, whereas reflex bradycardias associated with norepinephrine pressor activity were potentiated by clonidine. Norepinephrine-induced bradycardia, although reduced, still persisted after chronic bilateral sinusectomy and these responses were also potentiated by clonidine. In contrast, clonidine did not potentiate reflex bradycardia in dogs 20 days after aortic stripping. In intact dogs, clonidine inhibited the response to bilateral carotid artery occlusion and to carotid sinus nerve stimulation. These studies suggest that clonidine can inhibit carotid sinus baroreceptor function and simultaneously potentiate other, presumably aortic, baroreceptor activity.

The role of afferent barosensory neurons in respiratory and bronchomotor control

Ventilatory and bronchomotor responses to baroreceptor afferent stimulation were studied in anaesthetized rabbits breathing spontaneously. The stimuli used were either the increase in carotid sinus pressure or the electrical stimulation of the cut central end of the aortic nerve. Respiratory effects of aortic barodenervation were also studied. Normoxic, normocapnic steady state was verified by repeated measurement of PO2, PCO2 and pH in arterial blood. Stimulation of both aortic and carotid baroreceptors provoked an early decrease of tidal volume and total pulmonary resistances without change in respiratory frequency. Aortic nerve stimulation induced an important and slowly adapting ventilatory and bronchomotor effect, whereas changes in carotid sinus pressure produced slight variation in respiratory parameters. Aortic nerve section resulted in an early and prolonged increase of total pulmonary resistances. Surgical or chemical (atropine) vagotomy did not change the bronchodilation observed under stimulation of the carotid sinus; however this effect was suppressed by intravenous injection of propranolol. This observation shows the importance of the sympathetic outflow in the genesis of bronchomotor responses following baroreceptor stimulation. In conclusion the baroreceptor stimulation provokes simultaneous decrease of both ventilation and total pulmonary resistances; aortic nerves seemed to exert permanent control on bronchomotor tone.

Modification of the reflex response to stimulation of carotid sinus baroreceptors during and following stimulation of the hypothalamic defence area in the cat.

1. The effects of stimulation of the hypothalamic defence area on carotid sinus baroreceptor reflexes have been investigated by examining the cardiovascular responses to a 15 sec period of increased pressure within the vascularly isolated carotid sinus before, during, and immediately following a 25 sec period of hypothalamic stimulation.2. Identification of the hypothalamic defence area was based on the occurence of atropine-sensitive muscle vasodilatation. Electrode positions were confirmed by histological examination.3. During hypothalamic stimulation the reflex fall in blood pressure resulting from a rise in sinus pressure was found to be undiminished whether sinus pressure was raised at the onset or at the 10th sec of hypothalamic stimulation.4. By contrast, in at least half the cats in which a reflex bradycardia could be evoked from the sinus, this bradycardia was largely if not completely suppressed during hypothalamic stimulation. This suppression of reflex bradycardia occurred when sinus pressure was raised at the onset as well as at the 10th sec of stimulation.5. During the first 5 sec after hypothalamic stimulation the hypotensive response to an increase in carotid sinus pressure was much reduced; on the other hand the reduction in heart rate was exaggerated, sometimes to a very marked degree.6. The results suggest that stimulation of the hypothalamic defence area can modify baroreceptor reflexes and that this modification can include selective alterations in the various components of the reflex response.