The vasomotor component of the carotid sinus baroreceptor reflex in the cat during stimulation of the hypothalamic defence area

1. The effect of moderate intensities of stimulation of the hypothalamic defence area on the baroreceptor reflex has been investigated in the cat by comparing the responses of arterial blood pressure and perfusion pressure of the isolated hind-limb muscle bed perfused at constant volume inflow, when the isolated carotid sinus was subjected to a series of non-pulsatile pressures with and without simultaneous hypothalamic stimulation.2. In the absence of hypothalamic stimulation the characteristic sigmoid curves relating sinus pressure to blood pressure or muscle perfusion pressure were obtained.3. With simultaneous stimulation of the hypothalamus a similar sigmoid relationship was found. There was no evidence of any reduction in the over-all power or maximum sensitivity of the baroreceptor reflex.4. However, in those cats which had been atropinized to abolish the cholinergically mediated muscle vasodilatation, the curves obtained during hypothalamic stimulation were displaced in such a manner as to suggest that, while baroreceptor modulation of vasoconstrictor tone continued during defence area stimulation, the blood pressure regulating mechanism had been ;reset' so that, within the physiological range of sinus pressures, any given level of sinus pressure was associated with a greater vasoconstrictor tone.5. In non-atropinized cats there was little displacement of the curves relating sinus pressure to blood pressure, while the curves relating sinus pressure to muscle perfusion pressure were displaced in the opposite direction so that over-all muscle vascular resistance was less than normal at each level of sinus pressure.     

Evidence for the involvement in the baroreceptor reflex of a descending inhibitory pathway

1. The onset and time course of baroreceptor inhibition of pre- and post-ganglionic sympathetic reflex activity has been examined in the anaesthetized cat.2. The shortest time to the onset of inhibition of an intercostal evoked reflex response in cardiac and renal nerve was less than 90 msec following a rise in pressure in a carotid sinus blind sac, and around 55 msec following stimulation of the ipsilateral sinus nerve. The cardiac nerve response was completely inhibited before the renal nerve response.3. Because of the long delays in the somato-sympathetic reflex pathway it is argued that these minimum times will be much less than the real central delay of baroreceptor inhibition. These were estimated by adding on the central times for the somato-sympathetic reflexes to give latencies of 94-143 msec for the inhibition.4. A spinal sympathetic reflex was inhibited by 30-75% following a rise in pressure in a carotid sinus blind sac or sinus nerve stimulation. The minimum time for this inhibition was around 100 msec.5. The baroreceptor inhibition of the spinal sympathetic reflex was abolished following section of a restricted region in the dorsolateral part of the lateral funiculus of the cervical spinal cord.6. Both pre- and post-ganglionic reflexes could be inhibited when stimulating within three regions of the medulla oblongata. The latency to inhibition elicited from the ventromedial reticular formation was short, some 5-30 msec, whereas that elicited from a ventrolateral region or the mid line raphe nucleus was long, some 90-160 msec.7. The possibility is discussed that the baroreceptor inhibition of both the pre- and post-ganglionic reflexes examined in this study is occurring at the spinal level via a pathway from either the raphe nuclei or ventrolateral medulla.     

Adaptation of the human carotid baroreceptor-cardiac reflex.

1. Four intensities of neck suction were applied for 5 sec in healthy young men to determine the time course of decay of carotid baroreflex sinus node inhibition. 2. Peak responses occurred at about 1-25 sec after the onset of baroreceptor stimulation and were proportional to the intensity of stimulation. 3. Responses declined steadily during the remaining period of stimulation; the rate of decay of sinus node inhibition was decribed well by a power function and was proportional to the intensity of baroreceptor stimulation. 4. beta-adrenergic blockade did not alter the rate of decay of abroreflex sinus node inhibition. 5. These results suggests that adaptation of the integrated baroreceptor-cardiac reflex occurs in man and follows the same time course as adaptation of individual baroreceptor units an experimental animals.     

Baroreceptor sensitive neurones in the anterior hypothalamus of the cat

1. The activity of 372 neurones, located within or close to the hypothalamic depressor area, was recorded on raising the pressure within a vascularly isolated carotid sinus.2. When the intrasinusal pressure was raised abruptly to 200 mm Hg the activity of fifteen neurones was enhanced and of six inhibited.3. The neurones exhibiting excitation on baroreceptor afferent stimulation were broadly divisible into two groups. Nine neurones responded with a marked increase in discharge frequency, the other six responded with a ;burst-on' discharge with a minimum latency of 90 msec. Excitation in both cases was always within 500 msec of the presentation of the stimulus. No functional distinction has been drawn from these responses.4. Evidence has been obtained suggesting that the responses of both types of neurone showing excitation may be potentiated using a pulsatile rather than static stimulus.5. The role of the neurones in the integration of the carotid sinus baroreceptor reflex is discussed. It is suggested that the hypothalamic depressor area represents the rostral extension of the integrative centre for the reflex.     

Arterial baroreceptor reflex control of heart rate in two species of turtle

Attempts were made to stimulate an arterial baroreceptor reflex in anesthetized and conscious pond turtles. In turtles anesthetized with either alpha-chloralose or pentobarbital, occlusion of the ascending or descending aortas produced no reflex heart rate (HR) changes. In pentobarbital-anesthetized turtles, direct electrical or mechanical stimulation of potential baroreceptor sites along the central aortic arches and carotid arteries produced no significant changes in either HR or blood pressure (BP). Occlusion of the common carotid arteries also produced no HR or BP changes. Intravenously administered nitroglycerin lowered BP but caused no reflex tachycardia in anesthetized turtles. Phenylephrine and angiotensin elevated BP in the anesthetized turtle but caused no reflex bradycardia. In conscious turtles phenylephrine increased BP and nitroglycerin decreased BP. Neither response produced a statistically significant HR change, although HR tended to decrease transiently with phenylephrine and increase with nitroglycerin. These HR changes were abolished by atropine. Rapid intra-arterial infusion of 6% dextran transiently raised BP but caused no reflex bradycardia. These experiments suggest that cardiovascular regulation in the turtle is accomplished without a major contribution from arterial baroreceptor reflexes.     

Differentiated Interaction between the Hypothalamic Defence Reaction and Baroreceptor Reflexes

As the interrelationship of autonomic patterns involving cortico-hypothalamic and bulbar levels is of general interest, the interaction between the hypothalamic defence reaction and the homeostatic baroreceptor reflexes was explored in cats with respect to cardiac as well as vascular effects. The results suggest, in conformity with Hilton's observations (1963), that defence area stimulation suppresses the baroreceptor reflex inhibition of the heart. On the other hand, the baroreceptor influence on vasoconstrictor fibre discharge was largely the same, whether defence area stimulations were performed or not. This had important haemodynamic consequences, especially for muscle blood flow, since the reflex inhibition of regional constrictor fibre tone could greatly enhance the cholinergic vasodilatation. Therefore such a differentiated interaction between oppositely directed central and reflex autonomic mechanisms has the consequence that the baroreceptor reflexes, rather than damping the defence reaction, act in synergism with it with respect to net haemodynamic effects; some further implications of this are dealt with in the subsequent paper (Kylstra and Lisander 1969).     

Bradycardia evoked by hypothalamic stimulation in the rabbit: Dependence upon the arterial blood pressure

The spinal cord was transected in adult New Zealand White rabbits anaesthetized with urethane plus chloralose. The level of transection was in the mid-cervical region. The animals were then ventilated mechanically and the arterial blood pressure was maintained with an intravenous infusion of noradrenaline solution. Stimulation of the hypothalamus 1–2 mm lateral to the third ventricle and 1.5–3 mm dorsal to the mammillary nuclei, in a region known to evoke pressor responses and bradycardia in normal anaesthetized rabbits, never evoked pressor responses in the spinally transected rabbits. Bradycardia was evoked only when the mean arterial blood pressure was maintained above 44–49 mmHg. At higher pressures stimulation evoked a greater bradycardia and the relationship between bradycardia and pressure was approximately linear over much of the range of pressures tested (up to 116 mmHg).Because the threshold mean arterial blood pressure at which hypothalamic stimulation evoked bradycardia was similar to the threshold pressures reported in the literature for baroreceptor activation in the rabbit and because the curve of bradycardia:pressure was similar to published curves of baroreceptor and baroreflex activity against blood pressure, it is concluded that the bradycardia evoked by hypothalamic stimulation in the rabbit is mediated by a neural pathway in the hypothalamus that can increase the gain of the cardio-inhibitory baroreceptor reflex.     

Autonomic effector responses to stimulation of nucleus fastigius

1. In anaesthetized cats electrical stimulation of the nucleus fastigius caused cardiovascular responses, electrodermal responses of the paws and pupil dilation with retraction of the nictitating membranes.2. The cardiovascular responses included rise of arterial pressure and peripheral vasoconstriction. Increase of pulse pressure and tachycardia also occurred.3. The effects of sympathetic blocking drugs indicate that fastigial stimulation causes sympathetic discharge to the heart and to the peripheral vessels. There was no evidence of alteration of vagal activity.4. Fastigial stimulation inhibited reflex bradycardia due to carotid sinus distension, vagal afferent stimulation or phenyl diguanide.5. Fastigial and hypothalamic influences on cardiovascular responses could be evoked after severing the nervous pathways connecting the two.6. The pressor response to fastigial stimulation was still present after bilateral division of the carotid sinus and vagus nerves.     

The baroreceptor reflex and the cardiovascular changes associated with sustained muscular contraction in the cat

Summary In decerebrate unanaesthetised cats the cardiovascular effects of raising the pressure in a blind sac preparation of a carotid sinus on one side were examined at rest and during sustained contractions of hind-limb muscles. During a tetanic contraction the absolute value of the blood pressure and heart-rate components of the baroreceptor reflex response were not significantly changed from those at rest. The curve relating heart-rate and mean blood pressure, during carotid sinus distension, was similar at rest and when the muscles of the hind-limb were contracting tetanically, although each value of heart-rate was greater, suggesting a resetting of the baroreceptor reflex. By contrast, in the same experiments, suppression of the baroreceptor reflex changes in heart-rate and blood pressure could be demonstrated during the increases of blood pressure and heart-rate elicited by electrical stimulation of limb nerve. It was concluded that the increases in blood pressure and heart-rate elicited by the afferent discharge from muscles during sustained contraction are buffered to some extent by the baroreceptors, though their inhibitory effect is incomplete under these conditions.     

The role of the solitary and paramedian reticular nuclei in mediating cardiovascular reflex responses from carotid baro- and chemoreceptors

1. With dye-filled micro-electrodes single neurones in the medulla of anaesthetized paralysed cats were identified which: (a) fired rhythmically in synchrony with or were modulated by the cardiac cycle, and which ceased firing with occlusion of the ipsilateral common carotid artery (carotid sinus baroreceptor neurones); (b) were excited by stimulation of carotid body chemoreceptors by close intra-arterial injection of lobeline into the thyroid artery (carotid body chemoreceptor neurones).2. Twelve carotid baroreceptor neurones were identified, in thirty-three cats, nine of which were localized in the intermediate area of the nucleus of the solitary tract (NTS) within 1 mm ahead of or behind the obex; three units were located either in the parahypoglossal area or the dorsal portion of the paramedian reticular nucleus (PRN).3. Of the twenty-one carotid chemoreceptor neurones which were identified, thirteen were localized in the NTS, three in the parahypoglossal area and four in the dorsal PRN.4. Bilateral lesions of the paramedian reticular area of medulla destroying the PRN, abolished or reversed the depressor response to electrical stimulation of myelinated fibres of the carotid sinus nerve (CSN), attenuated the depressor response to carotid sinus stretch and augmented the pressor response to chemoreceptor stimulation by lobeline. Such lesions did not significantly alter the reflex heart rate responses.5. Small lesions of the NTS within an area 1 mm rostral to the obex abolished all reflex blood pressure and heart rate responses to electrical stimulation of the CSN or natural stimulation of carotid baro- or chemoreceptors.6. Baroreceptors and chemoreceptors of the CSN project both to the intermediate zone of the NTS and to more medial areas of the medulla, particularly the dorsal PRN and parahypoglossal area.7. The PRN serves to mediate the reflex depressor, but not cardio-vagal, response from myelinated baroreceptors and buffers the pressor responses from chemoreceptors; it may serve as an important area integrating cardiovascular activity descending from forebrain, brain stem and cerebellum with baroreceptor reflexes.8. Cardiovascular reflex responses arising from non-myelinated baroreceptors and all chemoreceptors are mediated by neurones in the intermediate area of the NTS.     

The relative roles of the aortic and carotid sinus nerves in the rabbit in the control of respiration and circulation during arterial hypoxia and hypercapnia

1. The respiratory and circulatory effects of graded arterial hypoxia, alone or with superadded hypercapnia, were studied in four groups of unanaesthetized rabbits including normal animals and those with selective section of the aortic nerves, selective section of the carotid sinus nerves and section of both sets of nerves.

2. When measured 2-4 days after selective section of the carotid sinus nerves the resting respiratory minute volume and arterial P_O2 were lower and the P_CO2 higher than normal. These effects were not observed after selective section of the aortic nerves. Selective aortic nerve section, and selective carotid sinus nerve section each produced a similar increase in the resting arterial pressure and heart rate, but were without effect on the resting cardiac output.

3. During arterial hypoxia reflex respiratory and circulatory effects ascribable to arterial chemoreceptor stimulation (hyperventilation, bradycardia, vasoconstriction) were mediated for the most part through the carotid sinus nerve. In animals with only the aortic nerves intact the circulatory response was determined largely by the opposing effects of aortic baroreceptor reflexes and the local peripheral dilator action of hypoxia.

4. The circulatory effects of hyperventilation induced by hypercapnia during arterial hypoxia, in animals with both aortic and carotid sinus nerves cut were small.

5. The results suggest that relatively few chemoreceptor fibres originate from the aortic region in the rabbit, though the carotid sinus and aortic nerves both contain baroreceptor fibres.

     

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).     

The localization of the first synapse in the carotid sinus baroreceptor reflex pathway and its alteration of the afferent input

Summary In 78 anaesthetized cats the lower brain stem was explored with microelectrodes for localization of the secondary neurones of the carotid sinus primary afferents. By means of recording single unit activities and evoked potentials (E.P.) by stimulation of the carotid sinus nerve (CSN) these neurones were located exclusively in the nucleus tractus solitarius (NTS) at the level of the obex.The E. P. was recorded with both ipsilateral and contralateral CSN stimulation.During repetitive stimulation of the CSN the frequency transmission across the synapse showed a sharp frequency limitation. With 10 Imp/sec the amplitude of the E.P. was only 50% of the maximal amplitude obtained with 1 Imp/sec. This frequency limitation is also manifested in the frequency effectiveness of the whole baroreceptor reflex measured as blood pressure reduction. It showed a maximum with frequencies of 20–30 Imp/sec, while stimulation of the secondary neurones in the NTS showed an increase in blood pressure reduction up to the tested frequencies of 120 Imp/sec.The E.P. was tested in the different phases of the respiratory cycle. No difference in amplitude or latency between the E.P. was noted.The relevance of these findings to the arrangement of the central neural substrates for the cardiovascular control is discussed.This work was supported by the Deutsche Forschungsgemeinschaft.A summary of these studies was presented at the 34. Tagung der Deutschen Physiologischen Gesellschaft [46].     

Cardiac reflexes during chronic nociceptive stimulation

Summary Repeated experiments were carried out on four dogs to study the influence of chronic stimulations with pain on the oculo-cardiac reflex and the reflex from the carotid sinus to the heart during compression of both common carotid arteries.A focus of chronic stimulation with pain was produced by placement on the sciatic nerve of two ligatures with tiny beads strung on them. The ligatures were drawn up and sutured to muscles in opposite directions. After a focus of irritation with pain had been produced, investigations were carried out during three to three and a half months. The changes in reflexes occurred by phases: during 15–20 days there was a distortion of reflexes, i.e., quickening of the pulse-rate upon pressure applied to the eyeball and a slowdown of the pulse upon compression of the carotid arteries. The reflexes returned to normal two and a half to three months after a focus of irritation with pain had been produced. Through all the period of investigations one could observe bradycardia (by 12–30 beats per min) as compared to the initial, painless, experiments.Scientific Director, Professor S. M. Dionesov (Presented by Active Member of the Academy of Medical Sciences of the USSR, V. V. Parin). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 62, No. 10, pp. 24–26, October, 1966.     

Circulatory effects of carotid sinus stimulation and changes in blood volume distribution in hypertensive man

In 8 patients with moderate hypertension and 8 normotensive subjects an attempt was made to study the circulatory effects of high and low pressure baroreceptor stimulation. Intrathoracic low pressure receptors were stimulated by changes in blood volume distribution using lower body negative pressure (LBNP) and lower body positive pressure (LBPP). The carotid sinus was stimulated by sinusoidal neck suction. Blood pressure, central venous pressure, heart rate, cardiac output and forearm blood flow were recorded. During LBNP and LBPP changes in central blood volume, reflected in changes in central venous pressure, induced significantly greater changes in cardiac output and forearm blood flow in the hypertensive subjects. In both normotensive and hypertensive subjects mean arterial blood pressure was essentially unchanged during LBNP and a slight increase was found during LBPP. Heart rate and blood pressure response to stimulation of the carotid sinus decreased with increasing resting mean arterial pressure. The results suggest impairment of reflex adjustments, via arterial baroreceptors, possibly in particular to dynamic stimuli, rather than via intrathoracic “low pressure” baroreceptors in subjects with moderate hypertension.     

Analysis of hemodynamic responses to hypothalamic stimulation in waking animals

Experiments on waking cats showed that electrical stimulation of protective zones of the hypothalamus leads to development of hypertension and inhibits baroreceptor reflexes. In animals with divided carotid sinus and aortic nerves, threshold hypothalamic stimulation leads to the appearance of depressor responses, whereas above-threshold stimulation evoked depressor-pressor responses. It is suggested that depression of baroreceptor reflexes is one of the mechanisms of the development of hypertension in response to hypothalamic stimulation.Department of Experimental Physiology and Pharmacology, Central Research Laboratory, I. P. Pavlov First Medical Institute, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the SSSR N. P. Bekhtereva.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 9, pp. 281–283, September, 1979.     

Participation of the anterior hypothalamus in the baroreceptor reflex

1. On the basis of discrete electrical stimulation in the pre-optic region and anterior hypothalamus of anaesthetized cats, a depressor area has been defined, stimulation of which elicits a fall of arterial blood pressure of 30-50 mm Hg and a bradycardia of some 25%, caused by inhibition of sympathetic vasomotor tone and by vagal activation respectively. These are accompanied by a reduction in rate and depth of respiration.2. The depressor area, from which this pattern of response is elicited, lies ventral and caudal to the anterior commissure, and extends caudally in the dorsal hypothalamus, dorsal to the fornix.3. The pattern of response elicited from identified points in the depressor area was shown to be indistinguishable from that to baroreceptor afferent stimulation.4. A lesion destroying the hypothalamic depressor area bilaterally reduced the response to baroreceptor afferent stimulation. Lesions in the medullary depressor area which spared a large part of the nucleus of the tractus solitarius also reduced, but did not abolish, the baroreceptor reflex response. The two lesions combined abolished the reflex.5. It is concluded that the whole brain-stem depressor area, from the hypothalamus through the mid-brain to the medulla, constitutes a functional unit which integrates the response to baroreceptor afferent stimulation.     

Depressed responsiveness of the carotid sinus reflex in conscious newborn animals.

The responsiveness of the carotid sinus reflex was evaluated by comparing the effects of bilateral carotid occlusion (BCO) in conscious adult dogs and puppies on measurements of arterial pressure, cardiac output, heart rate, and calculations of total peripheral resistance (TPR). In eight adult dogs, BCO increased mean arterial pressure by 57 +/- 6%, TPR by 48 +/- 5%, and heart rate by 45 +/- 15%. In puppies, BCO induced smaller increases (P less than 0.05) in mean arterial pressure (30 +/- 5%) and TPR (29 +/- 4%), while heart rate did not change. After elimination of opposing vagal and aortic baroreceptor reflexes, the differences in responses to BCO of mean arterial pressure and TPR between adults and newborns were even greater. Thus, the carotid baroreceptor reflex appears to be depressed in the newborn when compared with the fully developed reflex in the normal, conscious adult.     

The cause of the difference between the arterial baroreceptor reflex under natural pulsatile circulation and under nonpulsatile systemic circulation

In a previous study we investigated the relation between afferent and efferent activity of the arterial baroreceptor reflex under nonpulsatile systemic circulation using total left heart bypass. The results indicated that the regulation of the arterial baroreceptor reflex was converted under nonpulsatile systemic circulation, and we inferred that a possible reason for this conversion was the transformation in discharge of the afferent activity of the arterial baroreceptor reflex that took place under nonpulsatile systemic circulation. In the present study we tested this hypothesis by sectioning carotid sinus and aortic depressor nerves and electrically stimulating bilateral aortic depressor nerves under anesthesia in five rabbits (400 spikes for 20s, with 0.02ms pulse width and 8 V amplitude), while recording changes in aortic pressure, mean aortic pressure, and heart rate. Continuous stimulation was taken as discharge of the afferent activity of the arterial baroreceptor reflex under nonpulsatile systemic circulation, and periodic stimulation was taken as discharge under natural pulsatile circulation. Aortic pressure, mean aortic pressure, and heart rate decreased under both continous and periodic stimulation. The decreases in mean aortic pressure and heart rate during continuous stimulation were significantly lower than those during periodic stimulation. Our results suggest that the transformation in discharge of the afferent activity of the arterial baroreceptor reflex under nonpulsatile systemic circulation may have played an important causative role in the conversion of the regulation of the arterial baroreceptor reflex under nonpulsatile systemic circulation.     

Studies on the central integration of excitatory chemoreceptor influences and inhibitory baroreceptor and cardiac receptor influences.

Experiments were performed on cats to explore the integrated cardiovascular responses when excitatory (chemoreceptor) and inhibitory (baroreceptor or cardiac receptor) influences are simultaneously presented to the medullary cardiovascular areas. At a given sinus pressure in the low or medium pressure range, the systemic blood pressure and the vascular resistance were higher when the chemoreceptors were stimulated, while a high, pulsating sinus pressure, i.e.a strong baroreceptor stimulation, could suppress completely even an intense chemoreceptor activation. Thus, the set point and the gain of the baroreflex were increased by a concomitant chemoreceptor activation. These effects are compatible with a simple, mutual 'summation' of excitatory and inhibitory influences on a common population of central vasomotor neurons. The reflex vasodilator effects elicited via vagal cardiac afferents were found to be more effectively suppressed by a concomitant chemoreceptor stimulation than were the baroreceptor effects, provided a primary chemoreceptor response (bradycardia) was at hand, while the heart rate responses were essentially uninfluenced by the prevailing chemoreceptor activity. This chemoreceptor suppression of the reflex vasodilatation from cardiac receptors, which may be of great importance in hypoxic situations, e.g. during a dive, suggests a more complex, neuronal interaction between the two reflex mechanisms in the CNS.