Baroreceptor Reflex Arc Research Articles

Baroreceptor reflex enhancement by chronic intracerebroventricular infusion of enalapril in normotensive rats.

Involvement of the brain renin-angiotensin system in baroreceptor reflex regulation was assessed by recording reflex heart rate and sympathetic nerve responses in normotensive rats that had been infused intracerebroventricularly with the converting enzyme inhibitor enalapril for 15 days. Reflex bradycardia and sympathetic nerve inhibition during pressor responses to phenylephrine were larger in rats with intracerebroventricularly infused enalapril than in control rats similarly infused either intracerebroventricularly with saline or intravenously with enalapril. In contrast, opposite reflex responses to sodium nitroprusside-induced hypotension were mostly unaffected. Because depressor, bradycardic, and sympathoinhibitory responses to electrical stimulation of the central cut end of the left aortic depressor nerve were also enhanced, intracerebroventricularly infused enalapril must be affecting the baroreceptor reflex arc centrally. These results are compatible with the interpretation that intracerebroventricularly infused enalapril enhanced baroreceptor reflex sensitivity by reducing endogenous angiotensin II levels in the brain through converting enzyme inhibition.

Cardiovascular effects of substance P peptides in the nucleus of the solitary tract

Microinjection of the neuropeptide substance P (SP) into the baroreceptor portions of the nucleus of the solitary tract (NTS) caused a dose-dependent decrease in blood pressure (BP) and heart rate (HR), consistent with the putative role for SP as a transmitter in the baroreceptor reflex arc. In contrast, SP elevated BP and HR when microinjected into the adjacent area postrema. Structure-activity studies of effects of SP in the NTS revealed that an aminoterminal heptapeptide fragment of SP could fully reproduce the depressor and bradycardiac effects of SP. In contrast, a car☐yterminal hexapeptide fragment of SP significantly elevated both BP and HR. The structural requirements for aminoterminal fragment effects were quite specific in terms of peptide length and sensitivity to D-amino acid substitutions. These findings are consistent with a role for SP as a baroreceptor reflex transmitter and suggest, furthermore, that this action is mediated by the aminoterminal region of SP.

Excitotoxin-induced lesions of the central but not basolateral nucleus of the amygdala modulate the baroreceptor heart rate reflex in conscious rats

The present study has examined the influence of the central nucleus of the amygdala (Ce) and the basolateral nucleus of the amygdala (BL) on the baroreceptor heart rate (HR) reflex in conscious, unrestrained rats. Baroreceptor HR reflex activity was examined in rats with bilateral excitotoxin ( N-methyl- d-aspartate; 40 nmol/side)-induced lesions of the Ce or the BL and in control rats (artificial cerebrospinal fluid). After lesioning, the reflex HR responses were recorded following intravenous bolus doses of the pressor agent phenylephrine and the depressor agent sodium nitroprusside. Baroreceptor reflex parameters were determined by sigmoidal computerized curve-fitting. Lesions of either the Ce or the BL failed to effect resting mean arterial pressure (MAP) or HR. However, the Ce lesion reduced the maximum and average gain (sensitivity) of the baroreceptor reflex, and diminished the range of the reflex by altering the minimum, but not the maximum HR plateau. The upper and lower reflex thresholds and the MAP value corresponding to the midpoint of the HR range were not affected. Bilateral lesions of the BL failed to modify any baroreceptor reflex parameters. These results suggest that despite previous evidence for the involvement of the BL in cardiovascular regulation this nucleus does not exert a tonic influence on vasomotor neurons nor does it influence the baroreceptor HR reflex. In contrast, neurons projectinf from the Ce appear to provide excitatory input to medullary neurons involved in baroreceptor reflex arc regulation.

Glycine, like glutamate, microinjected into the nucleus tractus solitarii of rat decreases arterial pressure and heart rate

Glycinergic mechanisms have been implicated in central cardiovascular regulation. However, the inhibitory amino acid's role in the nucleus tractus solitarii (NTS), the site of termination of cardiovascular afferents, has not been clarified. Thus, we sought to determine if the microinjection of glycine into the NTS alters arterial pressure and heart rate. Microinjections of glycine, like glutamate, confined to the NTS decreased arterial pressure and heart rate in a neurally mediated, dose-dependent manner. The glycine antagonist strychnine completely blocked these effects of glycine but did not itself alter pressure or heart rate, or interfere with the baroreceptor reflex. The acute hypotensive, bradycardic response to glycine was followed by a period during which glycine essentially eliminated the cardiovascular responses to the microinjection into the NTS of glutamate, an amino acid reputed to be a transmitter in the baroreceptor reflex arc. These data suggest that glycine is involved in cardiovascular regulation by the NTS but do not support its being an integral transmitter in the baroreceptor reflex.

Baroreceptor stimulation alters pain sensation depending on tonic blood pressure.

ABSTRACTIt has been hypothesized that activation of the baroreceptor reflex arc, by its central nervous inhibitory effects, is involved in an operant learning mechanism of blood pressure elevation. The present study investigated the effects of mechanical stimulation of the baroreceptors in the carotid sinus on pain threshold and electrical brain activity in two groups of humans with different tonic blood pressure levels. In normotensives, baroreceptor stimulation lowered pain threshold as compared to a control condition, while borderline hypertensives tolerated more intense electric stimulation when baroreceptors were activated. A marked reduction of the contingent negative variation in anticipation of the aversive stimulation accompanied baroreceptor stimulation, probably a consequence of baroreceptor afferent impulses exerted via brainstem centers to cerebral cortex. The distribution of the potential change across the scalp depended on the tonic blood pressure, indicating differences in brain functioning between normotensives and borderline hypertensives.The present results suggest that the hypothesis of an operantly‐conditioned blood pressure elevation under stress may be valid only in subjects with a predisposition for essential hypertension.

Medial prefrontal cortical lesions modulate baroreflex sensitivity in the rat

Previous neuroanatomical studies in rats have demonstrated that the medial prefrontal cortex sends projections to the nucleus of the solitary tract which also receives the bulk of baroreceptor information from primary afferents within the IXth and Xth cranial nerves. The present study examines the influence of the prefrontal cortex on baroreceptor heart rate reflex in conscious rats. Baroreceptor reflex activity was examined in rats with bilateral excitotoxin ( N-methyl- d-aspartate )-induced lesions of the medial prefrontal cortex and in control rats (artificial cerebrospinal fluid). Seventeen to eighteen days after lesioning, reflex heart rate responses were recorded following intravenous bolus doses of the pressor agent phenylephrine and the depressor agent sodium nitroprusside. Baroreceptor reflex parameters i.e., maximum and average baroreceptor reflex gain (or sensitivity): minimum and maximum heart rate plateaus; heart rate range; upper and lower reflex thresholds were determined by sigmoidal computerized curve-fitting. Lesioning the medial prefrontal cortex did not affect resting mean arterial pressure and heart rate. However, the lesion reduced maximum and average baroreceptor reflex gain and produced a small reduction in lower reflex threshold. The other parameters were unaffected by the lesion. These observations suggest that although the medial prefrontal cortex does not exert a tonic influence or brainstem vasomotor neurons, there may be a descending excitatory projection from this brain region to medullary neurones involved in the baroreceptor reflex arc.

Valsalva's maneuver for evaluating the integrity of baroreceptor reflex arc

Valsalva's maneuver for evaluating the integrity of baroreceptor reflex arc

Valsalva's Maneuver for Evaluating the Integrity of Baroreceptor Relfex Arc

<h3>To the Editor.</h3> —Valsalva's maneuver is widely regarded as a reliable method to evaluate the overall integrity of the baroreceptor reflex arc.^1-3The results we obtained in a 37-year-old woman, who underwent a glomectomy bilaterally because of the presence of carotid body tumors, do not seem to support this belief. The bilateral carotid sinus denervation produced by the operation caused marked tachycardia (120 to 170 beats per minute), sustained hypertension (170/105 mm Hg on the average) and, understandably, the loss of an adequate blood pressure control while our patient was standing. Other authors have observed similar findings in patients who have undergone glomectomy bilaterally.⁴ When the patient assumed an upright posture and tilted her head, intra-arterial blood pressure monitoring, performed using the Oxford method⁵17 months after her glomectomy, showed a sharp fall in blood pressure, followed by wide cyclic blood pressure variations (195/125 to 130/90 mm

Localization of Autonomic Nervous System Dysfunction in Dialysis Patients

Autonomic nervous system dysfunction has been described frequently in uremic patients. The purpose of this study is to determine the localization of this abnormality and to study the possible relationship between autonomic dysfunction and the occurrence of dialysis hypotension. Sixteen consecutive patients participated in the study, 5 of whom had a history of dialysis-induced hypotension. These 5 patients were compared to the other 11 as regards the cardiovascular response to isoproterenol infusion, tilt test and arteriovenous (AV) fistula occlusion. None of the responses to the above mentioned stimuli was significantly different between the 2 groups. In the whole study population, an index of parasympathetic control of heart rate (variation of heart period, VHP) was reduced (31 +/- 5 vs. 59 +/- 9 ms in age-matched controls; p less than 0.025). Heart rate and diastolic blood pressure response to isoproterenol infusion was normal (+23 +/- 2 beats/min and -9 +/- 3 mm Hg; p less than 0.005 for both), indicating normal response of effector organs to beta-adrenergic agonist stimulation. Similarly, plasma norepinephrine increased significantly (+294 +/- 51 pg/ml; p = NS from normal laboratory values) in response to head-up tilt, and heart rate increased simultaneously in all but 5 patients. Blood pressure response was within normal after 10 min of head-up tilt at 60 degrees in all but 3 patients; only 1 of these 3 patients was in the group of dialysis hypotension. However, during AV fistula occlusion, heart rate did not change markedly, despite the significant increase in systolic blood pressure, suggesting an altered sensitivity of baroreceptor reflex arc.(ABSTRACT TRUNCATED AT 250 WORDS)

Serotonin receptors in the rat nucleus tractus solitarii and cardiovascular regulation

The effects of local application in the nucleus tractus solitarii of different serotonin receptor agonists and antagonists were investigated in anesthesized rats. Unilateral microinjection of serotonin produced an acute and transient hypotension and bradycardia which could be totally blocked by antagonists acting preferentially upon 5-HT 2 receptor binding sites: ketanserin and ritanserin. 5-HT 1 receptor agonists such as RU-24969 and 8-hydroxy-2-(di-n-propylamino)tetralin failed to reproduce the acute cardiovascular effects of serotonin. Bilateral microinjection of 5-HT 2 receptor antagonists produced an increase in the level and in the variability of arterial pressure but did not block the baroreceptor reflex arc. The data suggest that serotonin acting upon 5-HT 2 receptors in the nucleus tractus solitarii plays an important role in the modulation of arterial pressure.

Chlorpromazine: Cardiac arrhythmogenicity in the cat

To determine the effect of chlorpromazine on ouabain-induced arrhythmia and death, dial-urethane anesthetized cats were pretreated with chlorpromazine (5, 10, 20, 30, 40, or 60 mg/kg, i.v.) and then administered ouabain (2 ug/kg/min, i.v.). Blood pressure, heart rate and lead II electrocardiogram (ECG) were monitored. The dosages of ouabain necessary to induce premature ventricular contractions, ventricular tachycardia and death were determined. No significant correlation between the dose of chlorpromazine given and the dose of ouabain required to produce arryythmia or death was found. These doses of chlorpromazine could, therefore, be considered neither arrhythmogenic nor antiarrhythmic in the ouabain model. To determine whether chlorpromazine produced arrhythmia in the dial-urethane anesthetized cat model, the drug was infused at a rate of 1 mg/kg/min, i.v. Chlorpromazine produced arrhythmia at 185 ± 4.3 minutes and death via cardiovascular collapse at 128 ± 4.7 minutes. Bilateral adrenal vein ligation, employed to eliminate the influence of adrenal catecholamines, decreased the dosage of chlorpromazine necessary to produce arrhythmia and death to 67.8 ± 17.7 and 84.7 ± 15.7 mg/kg, respectively. Thus, adrenal catecholamines did not appear to contribute to chlorpromazine-induced arrhythmia, although the procedure of bilateral adrenal vein ligation appeared to be deleterious in combination with chlorpromazine. In all experiments, chlorpromazine depressed blood pressure without producing the reflex tachycardia normally seen with hypotension. This suggests that the drug may be interfering with the baroreceptor reflex arc. As chlorpromazine modifies the autonomic parameters of blood pressure, heart rate, and cardiac electrophysiology, sudden unexplained death in patients managed with this agent may be due to drug-induced arrhythmia.

Influence of age on cardiovascular reflex response in anesthetized rats.

To test the hypothesis that aging is associated with an altered hemodynamic response to physiological (nonpharmacological) stimuli, such as postural change and intravascular volume perturbations, we studied the adult (A, 6 mo) and senescent (S, 24 mo) Fischer 344 rat, a mammalian aging model not influenced by atherosclerosis or hypertension. Special emphasis was placed on the afferent limb of the baroreceptor reflex arc, an area not previously studied with respect to age. The base-line heart rate (HR), systemic arterial pressure (SAP), pulmonary arterial pressure (PAP), and carotid sinus nerve activity were not influenced by age. Following postural change (60 degrees upward tilt), the old animals demonstrated a greater drop in systolic pressure (-11 +/- 2, A; -21 +/- 4 mmHg, S; P less than 0.05), but there was no significant change in HR in either group. In response to a controlled withdrawal of 0.5 ml, the A had a greater reduction in systolic pressure (-29 +/- 4, A; -12 +/- 3 mmHg, S; P less than 0.01), whereas HR or PAP did not change; both groups showed a similar decrease in nerve activity. After infusions of 0.5 and 1.0 ml, the systolic and diastolic pressure changes were greater (P less than 0.02), and the changes in nerve activity appeared to be slightly more prolonged in the A compared with the S. Thus the response to changes in intravascular volume and posture are altered with age, and differences in volume-mediated venovasomotor reflex response may contribute to these age-related changes in the rat.

Interactions between cardiovascular and pain regulatory systems

A review of pharmacological, neuroanatomical, electrophysiological, and behavioral data indicates that systems controlling cardiovascular function are closely coupled to systems modulating the perception of pain. This view is directly supported by experiments from our laboratory showing that activation of either the cardiopulmonary baroreceptor reflex arc or the sinoaortic baroreceptor reflex arc induces antinociception. The outcomes of studies using pharmacological treatments, peripheral nerve stimulation, peripheral nerve resection, and CNS lesions are also presented as a preliminary means of characterizing cardiovascular input to pain regulatory systems. The network formed by these systems is proposed to participate in the elaboration of adaptive responses to physical and psychological stressors at various levels of the neuroaxis, and possibly to participate in “diseases of adaptation.” In particular, the present analysis suggests that the inhibition of pain brought about by elevations in either arterial or venous blood pressure may provide a form of psychophysiological relief under situations of stress and contribute to the development of essential hypertension in humans.

Modulation of cardiovascular and electrocortical activity through serotonergic mechanisms in the nucleus tractus solitarius of the rat

The nucleus tractus solitarius (NTS) is an integral part of the baroreceptor reflex arc. Thus, stimulation of the NTS elicits changes in arterial pressure and heart rate as well as in numerous other physiologic parameters including electrocortical activity. Serotonin (5-HT), which has been implicated in cardiovascular and electrocortical control, is present in nerve terminals within the NTS. Therefore, this study was designed to determine whether 5-HT may effect that control within the NTS. Serotonin injected into the NTS of anesthetized rats produced marked changes in the EEG, arterial pressure, and heart rate. EEG activity changed from irregular 1–5 Hz, 350–500 μV waves with an overlying 13–15 Hz, low voltage rhythm to a regular, 5 Hz, 250–300 μV rhythm. The dose-dependent cardiovascular changes were maximal at a dose of 400 pmol which produced a fall of mean arterial pressure of 48 ± 2mm Hg from a baseline of 96 ± 4mm Hg and of heart rate of 90 ± 9bpm from a baseline of 400 ± 18bpm( n= 6; P < 0.001). Both the cardiovascular and EEG effects of 5-HT injected into the NTS were blocked by the prior injection of the 5-HT antagonist metergoline at the same site. However, the bilateral microinjection of metergoline into the NTS did not affect the baroreceptor reflex. Thus, although serotonergic mechanisms in the NTS may be involved in the modulation of electrocortical and cardiovascular activity, they are not integral to the baroreceptor reflex arc.

Raphe neurons with sympathetic-related activity: baroreceptor responses and spinal connections.

We have previously used spike-triggered averaging to identify cat medullary raphe neurons with activity locked to the 2- to 6-cycles/s rhythm in sympathetic nerve discharge (SND) [Am. J. Physiol. 243 (Regulatory Integrative Comp. Physiol. 12): R49-R59, 1982]. In the present study, we classified such cat raphe neurons on the bases of their spinal connections and responses to baroreceptor reflex activation. Type I neurons, comprising 139 of 190 raphe units with activity related to inferior cardiac SND, were excited when carotid sinus pressure was elevated. The majority of these neurons were located in nucleus raphe pallidus. A time-controlled collision test for antidromic activation revealed that the axons of approximately one-third of type I neurons terminated in the sympathetic intermediolateral nucleus (IML) after coursing through the dorsolateral funiculus (DLF) of the spinal cord. The axons of the remaining type I neurons did not project to the spinal cord. It is suggested that type I raphe neurons are involved in mediating sympathoinhibition at spinal and supraspinal levels. Importantly, type I unit discharge remained locked to SND when the phase relationship between baroreceptor afferent and sympathetic efferent activities was disrupted. Thus type I neurons are not simple interneurons in the afferent limb of the baroreceptor reflex arc. Apparently they also receive input from the generator of the 2- to 6-cycles/s rhythm in SND. Type II raphe neurons (n = 51) were inhibited when carotid sinus pressure was elevated. Although the axons of these neurons coursed through the spinal DLF, they did not terminate in IML. Whether type II neurons subserve a sympathoexcitatory function remains to be determined.

Orthostatic Hypotension Associated With Hypothyroidism

SummaryWe report the case of a 65-year-old woman with highly symptomatic orthostatic hypotension associated with primary hypothyroidism. This orthostatic hypotension was caused by an autonomic dysfunction with a loss of integrity of the baroreceptor reflex arc and proved to be quite reversible with thyroid hormone replacement. We are unaware of such a clinical feature of hypothyroid autonomic neuropathy and suggest that hypothyroidism should be considered as an additional cause of orthostatic hypotension.

Normatensive and spontaneously-hypertensive rats show differences in sensitivity to arginine-vasopressin as a modulator of noradrenaline release from brainstem slices

The effect of arginine-vasopressin (AVP) on potassium ion-evoked release of [ 3H]noradrenaline (NA) from rat brainstem slices was investigated. In normotensive Sprague-Dawley (SD) and Wistar Kyoto (WKY) rats, AVP inhibited release of [ 3H]NA in a dose-dependent fashion, the magnitude and time course of inhibition at 10 −12 MAVP being similar to that observed using the α 2-adrenoceptor agonist, clonidine at 10 −7 M. However, it is unlikely that AVP functions through α-receptors since its effect is not blocked by phentolamine (10 −6 M). When brainstems from spontaneously-hypertensive (SH) rats (stroke-prone strain) were used, AVP was found to be without effect on [ 3H]NA-release at concentrations up to 10 −8 M. The potassium ion-evoked release appeared to have two components. The early phase of release was tetrodoxotin (TTX)-sensitive and was probably due to action potential conduction within the slices. The later phase, which was unaffected by tetrodotoxin, was probably a result of potassium-induced depolarization of nerve endings. AVP appeared to affect principally the early, TTX-sensitive release. In the presence of TTX (0.3 μM) the inhibitory effects of AVP were no longer seen. Thus, AVP may affect generation or conduction of action potentials within this tissue. There is published evidence that central vasopressinergic neurons may play a role in controlling the baroreceptor reflex arc. The present study provides a possible biochemical basis for this effect and is consistent with a neuromodulatory role of AVP in the CNS.

Activation of the sinoaortic baroreceptor reflex arc induces analgesia: Interactions between cardiovascular and endogenous pain inhibition systems

Two experiments examined the view that activation of the sinoaortic baroreceptor reflex arc induces analgesia. Rats were instrumented with carotid artery and jugular vein cannulae for measurement of arterial blood pressure, central venous blood pressure, and heart rate during assays of pain sensitivity using tail-flick responses to radiant heat. In Experiment 1, increases in arterial blood pressure effected by infusion of phenylephrine resulted in profound analgesia that persisted for a 28-min observation period following termination of the infusion. During the phenylephrine infusion period, the degree of analgesia was significantly correlated to the degree of reflex bradycardia, but was not significantly correlated to changes in either arterial or venous blood pressure. In Experiment 2, increases in arterial blood pressure effected by infusion of phenylephrine failed to induce analgesia in rats with bilateral sinoaortic deafferentations, indicating that activation of the sinoaortic baroreceptor reflex arc is required for this form of analgesia. As in Experiment 1, reflex bradycardia, rather than increases in arterial blood pressure, was correlated with analgesia. These outcomes are consistent with the view that systems involved in the regulation of blood pressure are physiologically linked to systems involved in the regulation of pain. The implications of these findings for the etiology of hypertension are discussed.

SYMPATHETIC NEURAL PROSTHESIS FOR MANAGING ORTHOSTATIC HYPOTENSION

A prototype electromechanical analogue of the sympathetic division of the baroreceptor reflex arc was used to maintain blood pressure automatically in two patients with neurogenic orthostatic hypotension. The device prevented significant and sustained reductions in mean blood pressure when the patients were tilted up to 85°. Upon achieving the preset mean blood pressure, the device maintained this pressure with a standard error of less than 2 mm Hg. Similar results were obtained when the patients were walking. The device did not cause supine hypertension during the trials.

Halothane and the carotid sinus reflex: evidence for multiple sites of action.

Baroreceptor reflexes have been found to be attenuated during halothane anesthesia in humans and experimental animals. The baroreceptor reflex arc is comprised for a number of components, including receptors, afferent and efferent nerve pathways, central integratory centers, peripheral ganglia, and effector organs, at which halothane might exert an inhibitory effect. This study was performed to determine the effect of halothane at each component in order to identify the site or sites of baroreflex attenuation due to halothane. The baroreflex effects on heart rate initiated by carotid sinus pressure changes were examined in conscious and anesthetized (0.0%, 0.75%, and 1.5% halothane in 50% N2O and O2, pls 25 mg/kg thiopental) dogs. In addition, carotid sinus afferent activity, cardiac sympathetic efferent activity and heart responses to direct sympathetic and parasympathetic efferent stimulation were examined in anesthetized dogs. Preganglionic and postganglionic sympathetic nerve activities were recorded simultaneously during baroreceptor activation to determine ganglionic effects of halothane. All levels of anesthesia significantly (P less than 0.05) attenuated reflex changes in heart rate produced by the pressure changes compared to conscious dogs. Significant decreases in cardiac sympathetic efferent activity were produced at 1.5% halothane (P less than 0.05). The depression in postganglionic activity was significantly greater than that or preganglionic activity, indicating a ganglionic-blocking effect by halothane. Cardiac chronotropic changes produced by direct efferent stimulation of sympathetic and vagal fibers were attenuated significantly by halothane (P less than 0.05). On the other hand, baroreceptor afferent activity was increased at 1.5% halothane. This sensitization of baroreceptors appeared to contribute to decreased levels of sympathetic tone, leading to blunted reflex changes in nerve activity. Therefore, halothane was found to have multiple sites of action, leading to depression of the baroreflex.