Circulatory control in hypoxia by the sympathetic nerves and adrenal medulla

1. The effects of severe arterial and primary tissue (carbon monoxide) hypoxia on cardiac output, arterial and right atrial pressures, heart rate and ventilation, have been studied in unanaesthetized normal rabbits, and in animals subjected to adrenalectomy, ;sympathectomy' (guanethidine), adrenalectomy + ;sympathectomy', and section of the carotid sinus and aortic nerves.2. In both arterial and primary tissue hypoxia the sympathetic nerves play a more important part in the normal circulatory response than the adrenal medullary hormones.3. Provided one adrenergic effector pathway remains intact, animals with intact chemoreceptors and baroreceptors tolerate both types of hypoxia well. Circulatory control during both types of hypoxia by means of sympathetic nerves alone produces relatively more peripheral vasoconstriction than is observed during reflex control through increased adrenal catecholamine secretion.4. The occurrence of tonic sympathetic activity in animals with section of carotid sinus and aortic nerves permits maintenance of a high cardiac output during hypoxia but the arterial pressure is low and there is probably less selective distribution of blood flow to the periphery than in animals with normal reflex control.5. Absence of any adrenergic activity in adrenalectomized and ;sympathectomized' animals results in a gradual fall in cardiac output during prolonged hypoxia, after an initial small rise.6. The results in guanethidine-treated animals suggest that the sympathetic discharge to the arterial chemoreceptors is a factor sustaining chemoreceptor discharge during prolonged arterial hypoxia.     

Restoration of reflex ventilatory response to hypoxia after removal of carotid bodies in the cat

In mammals there are two sets of peripheral arterial chemoreceptors, the carotid bodies innervated by the sinus branch of the glossopharyngeal nerve and the aortic bodies innervated by the vagus nerves. The afferent impulse discharge from both receptors increases during hypoxia and there is a reflexly mediated increase in ventilation (hypoxic hyperventilation). In the present study we tested this response by exposing anesthetized cats to decreased inspired O₂ concentration before and up to 315 days after bilateral resection of the carotid bodies. Acutely after removing the carotid bodies, hypoxic hyperventilation was abolished. This observation supports the view that the reflex pathway from the aortic body receptors normally contributes minimally to hypoxic hyperventilation. Subsequently, there was a restoration of hypoxic hyperventilation. Restoration was significant 30–43 days after removing the carotid bodies, it reached 70% of the preoperative value at 93–111 days and was essentially complete in terminal experiments 260–315 days after carotid body resection. In terminal experiments, hypoxic hyperventilation was not affected by recutting the regenerated carotid sinus nerves but was abolished completely by bilateral transection of the cervical vagosympathetic trunks. The restored ventilatory response was due predominantly to an increase in rate of breathing while an increase in tidal volume was predominant before carotid body resection. Resting ventilation breathing room air was not consistently decreased after carotid body resection while expired CO₂ was elevated from day 20 to day 111 and at the preoperative level in terminal experiments.It is concluded that restoration of hypoxic hyperventilation in the cat after carotid body resection is mediated by the reflex pathway from aortic body chemoreceptors. The possible contribution of chemo-receptive regenerated carotid sinus nerve axons was excluded. It is suggested that restoration may be a consequence of the central reorganization of chemoreceptor afferent pathways consequent to interruption of the carotid body reflex pathway and that as a result the ‘gain’ of the aortic body ventilatory chemoreflex is enhanced.     

Local and reflex factors affecting the distribution of the peripheral blood flow during arterial hypoxia in the rabbit

1. The effects of severe arterial hypoxia on the blood flow in the portal vein, and in kidney, muscle and skin beds have been determined in normal unanaesthetized rabbits, in animals without functioning autonomic effectors, and in rabbits with section of the carotid sinus and aortic nerves.

2. The resting blood flows in the above regions were not significantly different in the three groups.

3. The susceptibilities of the various beds to the local dilator effects of arterial hypoxia (assessed from the responses of animals without functioning autonomic effectors) were markedly different; vasodilatation was by far the greatest in the portal bed, followed in order by the renal, skin and muscle beds.

4. Section of the carotid sinus and aortic nerves completely abolished reflex activity, and the pattern of peripheral blood flow changes was similar to that of animals without functioning autonomic effectors. The findings suggest that the arterial chemoreceptors are the primary afferent source of reflex control of the peripheral circulation in arterial hypoxia.

5. In normal animals with intact reflexes there was sustained vasoconstriction throughout the treatment period in the portal and renal bed. The net vasomotor effects in muscle and limb skin were small owing to the operation of a number of factors, which opposed the effects of reflexly increased sympathetic nerve activity.

     

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

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

Efferent and afferent impulse activity recorded from few-fibre preparations of otherwise intact sinus and aortic nerves

1. In anaesthetized cats, the efferent discharge recorded from slips of otherwise intact sinus nerves was sparse in eupnoeic conditions but increased markedly during systemic hypoxia or asphyxia or following the injection of cyanide or acetaldehyde into the circulation of the ipsilateral carotid body.2. When the sinus nerve was cut distal to the efferent slip the responses to cyanide or acetaldehyde were abolished. The sparse ;resting' activity which remained was increased following the intravenous injection of adrenaline. Following distal section, the impulse traffic of the efferent slip did increase during systemic hypoxia but the response was much feebler than when the nerve was otherwise intact.3. The impulse activity of most efferent slips, peeled off from the otherwise intact sinus nerve, was abolished when the glossopharyngeal nerve was cut central to its junction with the same sinus nerve, indicating that the activity was probably recorded from genuine efferent units. The discharge of some ;efferent' preparations was still present, however, following such section and showed an increase to local injections of cyanide. This activity was probably recorded from looping or branching chemoreceptor afferents.4. The discharge of efferent slips of the cut aortic nerve was increased following the intravenous injection of adrenaline and during systemic hypoxia. These responses were not present when the vagus nerve was cut central to the nodose ganglion.5. In eupnoea, chemoreceptor afferent activity recorded from slips of the sinus or aortic nerves is much the same whether these nerves be otherwise intact or whether they be cut. During systemic hypoxia, chemoreceptor afferent discharge was less when it was recorded from the otherwise intact nerves than when these nerve trunks were cut.6. The cell bodies of sinus nerve efferent fibres are synaptically excited by chemoreceptor afferents coursing in the same nerve trunk. The increase of efferent impulse activity aroused by this means depresses chemoreceptor afferent discharge.     

The effects of haemorrhage in the unanaesthetized rabbit

1. The circulatory response following acute loss of 26% of the blood volume was examined in unanaesthetized rabbits. The groups of animals studied were normal rabbits; adrenalectomized rabbits; animals subjected to prolonged treatment with guanethidine in which peripheral adrenergic nerve transmission is blocked, but which can reflexly liberate adrenal medullary hormones; animals subjected to combined adrenalectomy and guanethidine treatment with no functional adrenergic effectors; in each case with or without administration of atropine. The responses of animals with section of the carotid sinus and aortic nerves were also examined.

2. The spontaneous rate of replacement of the blood volume after haemorrhage by reabsorption of extravascular fluid was the same in all the above preparations, the blood volume returning to normal 3-4 hr after bleeding.

3. The `passive' effects of haemorrhage were examined in animals without functioning autonomic effectors and include a large fall in right atrial pressure and cardiac output, arterial hypotension, no significant change in total peripheral resistance, and a bradycardia of gradual onset. Reflex autonomic effector activity in normal animals minimizes the fall in atrial pressure, cardiac output and arterial blood pressure, and produces a significant increase in total peripheral resistance and tachycardia. Increased sympathetic nerve activity and secretion of adrenal medullary hormones each play an important and complementary part in the normal circulatory response to haemorrhage of the rabbit. There is also reflex reduction in vagal efferent activity.

4. Reflexes from the carotid sinus and aortic arch limit the fall in arterial pressure for the first 4 hr after haemorrhage. These reflexes also account for the tachycardia normally observed after haemorrhage. The baroreceptor reflexes rather than the chemoreceptors appear to be dominant in these responses.

5. Twenty-four hours after haemorrhage the haemodynamic pattern is similar in all preparations irrespective of their autonomic effector status: blood volume, right atrial pressures and cardiac outputs are all elevated, and the arterial pressure has virtually recovered, consistent with the development of hypervolaemic anaemia at this time.

     

Arterial and cardiopulmonary baroreceptor and chemoreceptor influences and interactions on ear sympathetic nerve discharge in the rabbit

1. The effects of changing intravascular pressures on integrated ear sympathetic nerve activity (ESNA) were studied in anesthetized artificially ventilated rabbits by inflating aortic and inferior vena caval perivascular balloons under conditions of normal arterial Po2 and during arterial hypoxia. 2. At normal Po2 ESNA was unaffected by arterial and cardiopulmonary baroreflex influences. The small inhibition of ESNA observed during rises in arterial pressure after vagotomy was also present after section of the carotid sinus and aortic nerves, and after cutting both vagi as well. 3. During hypoxia there was marked inhibition of ESNA, which was minimally influenced by vagotomy but abolished by section of the carotid sinus and aortic nerves, suggesting that it was chemoreceptor-mediated. There was a pressure-related rise in ESNA which was abolished by vagotomy and considered to be due to a central nervous chemoreceptor-cardiopulmonary baroreflex interaction.     

The effects of electrical stimulation of the distal end of the cut sinus and aortic nerves on peripheral arterial chemoreceptor activity in the cat

1. In anaesthetized cats, stimulation of efferent components of the carotid sinus or aortic nerves depressed chemoreceptor discharge from the relevant chemoreceptor afferents. The local application of 2% procaine hydrochloride to the sinus nerve trunk, peripheral to the site of the stimulating electrodes and proximal to that of the afferent nerve twig, abolished the depression of afferent chemoreceptor discharge caused by electrical stimulation; on washing the procaine away electrical stimulation once more induced depression of chemoreceptor discharge.2. The depressant effect of efferent stimulation on carotid chemoreceptor activity was still seen during complete carotid glomeral ischaemia. Atropine given by close intra-arterial injection to the carotid body did not affect the depressant influence of efferent sinus nerve stimulation on carotid body chemoreceptor discharge.3. Stimulation of the sinus nerve efferents usually increased carotid body blood flow. Close arterial injection of atropine abolished this effect.4. The responses of glomeral blood flow and carotid chemoreceptor activity to efferent stimulation of the cut sinus nerve were not temporally related. It seems improbable that the depressant effect of such stimulation on chemoreceptor discharge was due to alterations of glomeral blood flow.5. Stimulation of the peripheral end of the cervical vagus in atropinized cats reduced chemoreceptor activity recorded in the ipsilateral aortic nerve.     

Hypoxia and hypercapnia increase the sympathoadrenal medullary functions in anesthetized, artificially ventilated rats

Graded hypoxia (FETO2 14-6%) and hypercapnia (FETCO2 6-10%), which were applied for 45s and 2 min, respectively, to urethane anesthetized and artificially ventilated rats produced an increase in adrenal sympathetic efferent nerve activity in parallel with increases in adrenaline and noradrenaline secretion measured in the adrenal venous effluent. Percentage increases in adrenaline and noradrenaline were almost equal. In rats whose carotid sinus nerves (CSN) were bilaterally cut, hypoxia did not produce any effect on adrenal sympathetic nerve activity or catecholamine secretion. In contrast, excitatory adrenal nerve and catecholamine secretory responses to hypercapnia remained unchanged in CSN denervated rats. After severing a splanchnic nerve whose branches innervated the adrenal gland, while maintaining the resting level of catecholamine secretion by low-frequency stimulation of the peripheral end of the splanchnic nerve, hypoxia did not produce any increase in catecholamine secretion. Hypercapnia (FETCO2 8 and 10%), however, induced catecholamine secretion from denervated adrenal medulla, although the magnitude of the response was significantly lower than that in animals with adrenal nerve intact. It is concluded that hypoxia stimulates the adrenal medulla via the carotid chemoreceptor reflex whereas hypercapnia acts mainly via mechanisms besides carotid chemoreceptors such as central chemoreceptors with some direct stimulatory effect on the adrenal medulla. The functional significance of these dual mechanisms of sympathoadrenal excitation during hypoxia and hypercapnia is discussed.     

Effects of arterial hypoxia on the cutaneous circulation of the rabbit

1. Changes in blood flow of the skin of the rabbit's ear and hind limb have been studied during arterial hypoxia by a calibrated heat conductivity method, together with changes in arterial pressure and aortic blood temperature.

2. There is little change in the blood flow of the hind-limb skin during the early phase of arterial hypoxia, reflecting a balance between the local dilator effects of hypoxia and the increased constrictor activity mediated through the sympathetic nerves as a result of arterial chemoreceptor excitation. During more prolonged arterial hypoxia there is a small gradual dilatation of the vessels of the hind-limb skin as a result of some diminution in the initial intensity of vasoconstrictor activity.

3. There is much more extensive vasodilatation in the ear than in the hind-limb skin during arterial hypoxia. Vasoconstrictor activity is slight in this region. Comparison of the ear responses to arterial and to primary tissue hypoxia suggests that in the former type of hypoxia stimulation of the arterial chemoreceptors inhibits thermoregulatory vasoconstriction to the ear, whilst in the latter type of hypoxia baroreceptor reflexes maintain or intensify it.

     

Effects of hyperventilation on the circulatory response of the rabbit to arterial hypoxia

1. The circulatory effects of artificial hyperventilation with air and low oxygen mixtures were studied in rabbits anaesthetized with chloralose-urethane and given decamethonium iodide. The role of vagal afferents in the response to hypoxia was also assessed in spontaneously breathing unanaesthetized and anaesthetized animals.2. In the anaesthetized rabbit artificial hyperventilation inhibited all the changes in autonomic activity to the heart and peripheral circulation resulting from stimulation of the arterial chemoreceptors, and also reduced vagal efferent tone. In animals with section of the carotid sinus and aortic nerves the changes in autonomic activity observed during hypoxia and hyperventilation were much smaller than in normal animals and affected only cardiac autonomic activity.3. The effects of hyperventilation during hypoxia were mediated chiefly through vagal afferents rather than through the effects of hypocapnia. In the absence of changes in autonomic activity (e.g. during artificial hyperventilation with air) the circulatory effects were small and less clearly related to afferent vagal activity.4. In the spontaneously breathing anaesthetized and unanaesthetized rabbit vagal afferent activity resulting from the respiratory response to hypoxia inhibits sympatho-adrenal activity in the same way as during hypoxia with artificial hyperventilation.5. The importance of the vagal afferent input in the rabbit is discussed in relation to the qualitative differences in circulatory response with increasing severity of hypoxia, and in relation to the effects of anaesthesia.     

Electron microscopic and electrophysiological studies on the carotid body following intracranial section of the glossopharyngeal nerve

1. The innervation of carotid body Type I cells has been investigated in seventeen cats. At a sterile operation the glossopharyngeal and vagus nerve roots were cut intracranially on one side.

2. From 1½ to 378 days after the operation the carotid bodies were fixed in situ and prepared for electron microscopy. Nerve endings on Type I cells were found to degenerate with a prolonged time course. In each cat there was a decrease in the number of nerve endings on the operated side as compared with the non-operated side.

3. Before the carotid bodies were fixed, recordings were made from chemoreceptor, and baroreceptor, afferent fibres in the sinus nerve on the operated side. The chemoreceptors responded in the usual way to changes in arterial O₂, CO₂ and pH; the injection of cyanide evoked a brisk response.

4. It is concluded that the nerve endings on Type I cells are efferent rather than afferent and the cell bodies of their axons are probably in the brain stem.

     

Baroreceptor and chemoreceptor influences on heart rate during the respiratory cycle in the dog.

1. Brief stimuli were delivered to the carotid chemoreceptors or baroreceptors in dogs anaesthetized with pentobarbitone or chloralose. Chemoreceptor stimulation was achieved by rapid retrograde injections of 0-2-0-5 ml. warmed, CO2-equilibrated saline through a cannula in the external carotid artery. Baroreceptor stimulation was achieved by forceful retrograde injection of 2-5 ml. air-equilibrated saline, or of freshly drawn arterial blood, into the external carotid artery after first clamping the common carotid artery. 2. Brief baroreceptor stimuli had no noticeable effect on breathing. Brief chemoreceptor stimuli had no effect on breathing in some dogs, but in many produced a reflex increase in the depth of inspiration when delivered during inspiration. In these same dogs, brief chemoreceptor stimuli delivered in expiration either prolonged the expiratory pause or evoked an active expiratory effort. 3. Prompt decreases in heart rate were elicited by brief sudden chemoreceptor or baroreceptor stimuli when these were delivered during the expiratory phase of respiration. The stimuli did not modify the control heart rate pattern when delivered during inspiration. If the carotid sinus nerve or the vagus nerves were cut the responses were abolished. 4. Brief chemoreceptor or baroreceptor stimuli remained effective in evoking prompt decreases in heart rate during periods of apnoea in the end-inspiratory position (Hering-Breuer inflation reflex). In periods of apnoea after prolonged artificial hyperventilation the stimuli were sometimes ineffective at first, but were always effective late in the period of apnoea, again producing prompt cardiac slowing. 5. After denervation of the lungs, brief baroreceptor and chemoreceptor stimuli continued to evoke prompt falls in heart rate when given during expiration. When delivered during inspiration the same stimuli were either ineffective, or less effective.     

Evidence for central reorganization of ventilatory chemoreflex pathways in the cat during regeneration of visceral afferents in the carotid sinus nerve

There are two sets of peripheral arterial chemoreceptors in the cat, the carotid bodies innervated by the carotid sinus nerve and the aortic bodies with afferents in the aortic depressor nerves. Reflex stimulation of ventilation in response to hypoxia is abolished acutely after interrupting the sensory pathway from the carotid body chemoreceptors in the cat even though the reflex pathway from the aortic body chemoreceptors is intact. However, in chronically maintained preparations, there is a restoration of the hypoxic response which is mediated by the aortic chemoreflex pathway. It was proposed that restoration was due to a ‘central reorganization’ of chemoreflex pathways which followed interruption of the sensory pathway from the carotid bodies and that the reorganization enhanced the efficacy of the aortic ventilation chemoreflex. This proposal was tested in the present experiments by measuring reflex ventilatory and cardiovascular responses to electrical stimulation of the sensory nerves containing aortic and carotid chemoreceptor afferents following bilateral interruption of carotid sinus nerves and carotid body resection. Responses measured acutely (1–6 h) after interruption were compared with those measured 60–80 and 110–140 days later. At 60–80 days, a chemoreflex response (increase in tidal volume of ventilation) to stimulation of the interrupted carotid sinus sensory pathway was markedly attenuated while the response to stimulation of the uninterrupted pathway in aortic depressor nerves was enhanced. At 110–140 days, the tidal volume response to carotid sinus nerve stimulation was greatly enhanced while the aortic depressor nerve response declined from the elevated level. There were significant but less pronounced changes in the response of other ventilatory and cardiovascular variables to aortic depressor nerve and carotid sinus nerve stimulation.The results support the idea that there is a ‘central reorganization’ of chemoreflex pathways which is reflected functionally by changes in the efficacy of reflexes evoked from aortic depressor nerve and carotid sinus nerve. The changes are analagous to those occurring in somatic reflexes during regeneration of sensory nerves. It is suggested that the changes in efficacy of carotid sinus nerve reflexes are due to a degenerative loss of synapses of the central projections of interrupted carotid sinus nerve sensory axons (degenerative atrophy) and subsequent regenerative like changes (regenerative proliferation) in the central projections. The changes in the efficacy of aortic depressor nerve reflexes may be attributed to formation of new synapses by converging central projections of this uninterrupted pathway (reactive synaptogenesis) and subsequent regression of the newly formed synapses.     

Degenerative and regenerative changes in central projections of glossopharyngeal and vagal sensory neurons after peripheral axotomy in cats: a structural basis for central reorganization of arterial chemoreflex pathways

Hypoxic hyperventilation in cats is a reflex normally initiated by afferent impulses originating in the carotid body and conducted to the brain stem by the carotid sinus nerves. The reflex response is abolished acutely after section of carotid sinus nerves and excision of the carotid bodies; but, chronically, there is a chemoreflex restoration which is mediated by the aortic body via the aortic depressor nerves. The restoration is associated temporally with changes in efficacy of ventilatory reflexes elicited by electrically stimulating carotid sinus and aortic depressor nerves, and these changes are postulated to reflect a central reorganization of the reflex pathways. In the present study, histological and ultrastructural techniques were used to investigate the neuroanatomical basis of the reorganization. The brain stem of the cat was examined using the Fink-Heimer silver stain to determine if degenerating axons were present following section of the carotid sinus nerve peripheral to its sensory ganglion. Degeneration was found 4-15 days postoperatively and the distribution of the axons corresponded with that reported for central projections of carotid sinus nerves labeled by transganglionic transport of horseradish peroxidase. The fine structure of nerve terminals in nucleus tractus solitarius was then examined with electron microscopy after cutting the vagus and glossopharyngeal nerves unilaterally peripheral to the sensory ganglia. Structural changes consistent with nerve terminal degeneration were observed 4-91 days postoperatively, and presumptive axonal sprouts were seen at 56-91 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Three types of neurochemically defined autonomic fibres innervate the carotid baroreceptor and chemoreceptor regions in the guinea-pig

Summary The innervation of the carotid body, carotid sinus, and neighbouring arteries (common carotid artery; external carotid artery; occipital artery; ascending pharyngeal artery) was investigated in guinea-pigs by means of glyoxylic acid-induced catecholamine-fluorescence and immunohistochemistry using a variety of antisera against neuropeptides and tyrosine hydroxylase (TH). Fibres displaying catecholamine-fluorescence, TH- and neuropeptide Y-like immunoreactivity (NPY-LI) were less numerous in the carotid sinus than in all other arterial segments. Vasoactive intestinal polypeptide (VIP)-LI axons were almost lacking in the common carotid, external carotid and occipital arteries, consistently found in the carotid sinus, and more numerous in the ascending pharyngeal artery. Catecholaminergic, TH-, NPY- and VIP-LI fibres were observed deep in the media of the carotid sinus, where the baroreceptor terminals are located. In contrast, they did not enter the media in the adjacent arterial segments. All these fibres disappeared following excision of the superior cervical ganglion, but were unaffected by combined transection of the carotid sinus nerve and resection of the nodose ganglion, suggesting a sympathetic origin. Doublestaining immunofluorescence revealed at least three types of autonomic, presumably sympathetic fibres in the carotid sinus: 1) TH⁺/NPY⁺, 2) NPY⁺/VIP⁺, and 3) VIP⁺ fibres. This points to a non-noradrenergic efferent innervation of the carotid sinus in addition to the hitherto known noradrenergic sympathetic fibres. The three populations of autonomic fibres seen in the carotid sinus were also observed in the carotid body, but the paucity of NPY⁺/VIP⁺ double-labelled fibres raises doubt as to the functional significance of this particular fibre type in modulating arterial chemoreception. The multiplicity of neurochemically defined autonomic nerves to the carotid baro- and chemoreceptor regions probably reflects functionally separate pathways that are differently regulated and exert different effects.     

Denervation of Carotid Baro- and Chemoreceptors in Humans

Experimental denervation in animals has shown that carotid baro- and chemoreceptors play an eminent role in maintaining blood pressure and blood gas homeostasis. Denervation of carotid sinus baro- and chemoreceptors in humans may occur as a complication of invasive interventions on the neck or after experimental surgical treatment in asthma. In this topical review, the short- and long-term effects of carotid baro- and chemoreceptor denervation on the control of circulation and ventilation in humans are discussed. Carotid baroreceptor denervation in humans causes a persistent decrease in vagal and sympathetic baroreflex sensitivity and an increase in blood pressure variability; however, carotid denervation does not lead to chronic hypertension. Therefore, although carotid baroreceptors contribute to short-term blood pressure control, other receptors are able to maintain normal chronic blood pressure levels in the absence of carotid baroreceptors. Conversely, carotid chemoreceptor denervation leads to permanent abolition of normocapnic ventilatory responses to hypoxia and reduced ventilatory responses to hypercapnia.     

The role of the carotid body chemoreceptors and carotid sinus baroreceptors in the control of cerebral blood vessels

1. Cerebral blood flow was measured in 17 baboons, anaesthetized with pentobarbitone, paralysed with gallamine and mechanically ventilated and in which the right sinus and both aortic nerves had been cut and the left carotid sinus vascularly isolated. Later in each experiment, the head was artificially perfused with femoral arterial blood via the innominate artery.2. Stimulation of the carotid body chemoreceptors with venous blood invariably caused a rise in regional cerebral blood flow whether the head was naturally or artificially perfused. This response was almost completely abolished if the VIIth cranial nerves were cut intracranially.3. Regional cerebral blood flow varied inversely with carotid sinus pressure.4. After the remaining (left) sinus nerve had been cut, the cerebral vascular response to hypoxia was negligible and the response to hypercapnia was markedly reduced. Blood flow then varied with perfusion pressure.5. These results provide further evidence that cerebral blood vessels are reflexly controlled and that the peripheral arterial receptors are involved. Their action is most conspicuous in the vascular response to hypoxia and together with intrinsic factors in the cerebral vascular bed, they determine the size of the vascular response to changes in CO(2) and pressure.     

The contribution of the arterial chemoreceptors to the stimulation of respiration by adrenaline and noradrenaline in the cat

1. Intravenous infusions of adrenaline and noradrenaline in doses averaging 0.8 mug/kg.min increased the respiratory minute volume of anaesthetized cats breathing room air. The mean increase in respiratory minute volume was 14% during adrenaline infusion and 8% during noradrenaline infusion.2. In a small group of decerebrate cats infusions of adrenaline and noradrenaline increased ventilation by 19 and 27% respectively.3. Intravenous catecholamine infusions also increased the respiratory responses of anaesthetized animals to the inhalation of 5% or 10% O(2) in N(2) and to the inhalation of 5% CO(2) in air.4. Adrenaline and noradrenaline infusions had no significant effect on the ventilation of animals breathing 100% O(2), nor did they significantly alter the respiratory response to the inhalation of 5% CO(2) in O(2).5. After section of the carotid sinus and aortic nerves, a blood-pressure compensator being used to minimize changes in arterial pressure, catecholamines had no effect on the respiration of cats breathing air.6. An increase in carotid body chemoreceptor discharge accompanied the increase in ventilation during catecholamine infusion.7. Intravenous catecholamine infusions still produced an increase in ventilation and carotid body chemoreceptor discharge after both aortic nerves and both cervical sympathetic nerves had been cut.8. Intra-arterial infusions into one carotid artery of 0.2 mug/kg.min of adrenaline or 0.1 mug/kg.min of noradrenaline led to mean increases in respiratory minute volume of 9.9 and 11.5% respectively. No increase occurred after section of the corresponding carotid sinus nerve. Such infusions also evoked an increase in carotid body chemoreceptor discharge.9. It is concluded that the hyperpnoea produced by adrenaline and noradrenaline infusions in the cat is predominantly reflex in origin and is mediated by the arterial chemoreceptors.10. The increase in ventilation produced by adrenaline appears to have a component additional to its effect upon the chemoreceptors though the nature of this action has not been identified.     

Pronounced depression by propofol on carotid body response to CO2 and K+-induced carotid body activation

Propofol is a commonly used anesthetic agent, and it attenuates hypoxic ventilatory response in humans. Propofol reduce in vivo and in vitro carotid body responses to hypoxia as well as to nicotine in experimental animals. In the present study we examined the effects of propofol on carotid body responses to hypercapnia and K(+)-induced carotid body activation and compared these effects with hypoxia in an in vitro rabbit carotid body preparation. Hypoxia, hypercapnia and potassium increased the carotid sinus nerve activity and propofol attenuated the chemoreceptor responses to all three stimuli. However, the magnitude of propofol-induced attenuation was greater for hypercapnic and K(+)-induced carotid body activation compared to the hypoxic response. These observations suggest that propofol-induced attenuation of the hypoxic response is partly secondary to depression of chemoreceptor response to hypercapnia inhibiting the synergistic interactions between O(2) and CO(2) and may involve CO(2)/H(+) sensitive K(+) channels.