Aortic Chemoreceptors Research Articles

Relative responses of aortic body and carotid body chemoreceptors to carboxyhemoglobinemia.

The effects of carbon monoxide inhalation and of consequent carboxyhemoglobinemia (HbCO) on the discharge rates of aortic body and carotid body chemoreceptor afferents were investigated in 18 anesthetized cats. In 10 experiments both aortic and carotid chemoreceptor activities were monitored simultaneously. Carbon monoxide inhalation during normoxia always stimulated aortic chemoreceptors before carotid chemoreceptors, and the steady-state response of aortic chemoreceptors to HbCO was greater than that of most carotid chemoreceptors. Only 2 of the 18 carotid chemoreceptor fibers tested showed a distinct increase in activity in response to moderate increases in HbCO%. Thus, oxyhemoglobin contributed substantially to maintain tissue PO2 of all aortic chemoreceptors and of a few carotid chemoreceptors. Hyperoxia diminished the response of both aortic and carotid chemoreceptors to HbCO, indicating a lowered tissue PO2 as the stimulus source. We hypothesize that the aortic bodies have a much lower perfusion relative to their O2 utilization compared to the carotid bodies. As a consequence, the aortic chemoreceptors are able to act as a sensitive monitor of O2 delivery and to generate a circulatory chemoreflex for O2 homeostasis. carotid chemoreceptors monitor O2 tension and initiate strong reflex effects on the level of ventilation.

Effect of peripheral chemoreceptor denervation on acclimatization of goats during hypoxia

The purpose of this study was to determine the effect of peripheral chemoreceptor denervation on ventilatory acclimatization of goats during chronic hypoxia. After 1 h of stimulated altitude (PB 450 Torr), arterial O2 tension (PaO2) in seven normal goats averaged 42 Torr, and arterial CO2 tension (PaCO2) was 1.3 Torr below control (P less than 0.001). In these goats nearly 66% of the increase in alveolar ventilation (VA) associated with acclimatization occurred between 1.5 and 4 h of hypoxia. Acclimatization was complete by the 3rd day of hypoxia, and it caused 1) a 23% increase in VA/CO2 output (P less than 0.001); 2) a 5-Torr increase in PaO2 (P less than 0.001); and 3) a 6.5-Torr decrease in PaCO2 (P less than 0.001). Denervation of the carotid chemoreceptors in seven goats caused hypoventilation during eupnea at sea level (PaCO2 change from control +7 Torr, P less than 0.001). Denervation also attenuated but did not eliminate peripheral chemoreceptor responsiveness. No additional changes were observed following attempted denervation of the aortic chemoreceptors. After 1 h of simulated altitude (PB 530 Torr), PaO2 in the denervated goats averaged 46 Torr, and PaCO2 was increased 1.1 Torr above control (P less than 0.001). In these goats VA did not change significantly during the subsequent 3 days of hypoxia. Accordingly, we conclude that the peripheral chemoreceptors are essential for ventilatory acclimatization of goats during chronic hypoxia.

Recovery of peripheral chemoreceptor function after denervation in ponies.

Resting ventilation (PaCO2) and ventilatory responses to acute hypoxia and to intravenous NaCN were assessed over a 4-yr period following cutting of the carotid sinus nerves and stripping the adventitia of the aortic arch. The data indicated essentially complete loss of peripheral chemoreceptor function immediately after surgery and hypoventilation during normoxia (delta PaCO2 = +8.7 Torr). There was a time-dependent, partial recovery of peripheral chemoreceptor function between 2 and 22 mo after surgery. Approximately 10% of the ventilatory response to iv NaCN returned, and 30-40% of the normal response to acute hypoxia was restored. Resting PaCO2 was no longer significantly elevated above normal by 22 mo after surgery. Four years after surgery these animals were unable to sustain normal ventilatory acclimatization to chronic hypoxia just as in an earlier study in the same ponies. Experiments carried out under anesthesia showed that recovered peripheral chemoreceptor sensitivity was not present in the carotid chemoreceptor area. However, sectioning of the aortic nerve caused the animals to again hypoventilate during acute hypoxia, and it nearly eliminated the ventilatory response to NaCN, but normal eucapnic ventilation was retained. We conclude that in the pony aortic chemoreceptors become functional in a time-dependent manner following carotid body denervation.

Relative responses of aortic body and carotid body chemoreceptors to hypotension.

Responses to acute arterial blood pressure changes of a single or a few chemoreceptor afferents from the aortic body and carotid body at constant arterial blood gases and pH were measured in 16 adult cats. During normocapnic normoxia and moderate hypoxia (arterial oxygen tension of 60 Torr) an induced hypotension of 80 Torr increased strikingly the discharge rate of all aortic chemoreceptors but not of most carotid chemoreceptors; hypotension down to the level of 50 Torr stimulated most carotid chemoreceptors only slightly. Hyperoxia eliminated the stimulatory effect of this degree of hypotension on carotid chemoreceptors; it did not affect aortic chemoreceptors to the same extent. Hypoxia augmented the effect on aortic chemoreceptors more than the effect on carotid chemoreceptors. Thus the effect of hypotension was dependent on arterial oxygen tension. The greater effect of hypotension on aortic body chemoreceptor activity indicates a greater normal circulatory constraint for the aortic body. Accordingly, aortic chemoreceptors are more suited to monitor circulatory changes in O2 flow, and carotid chemoreceptors are more suited to monitor arterial gas pressure changes due to respiration.

Relative latency of responses of chemoreceptor afferents from aortic and carotid bodies.

Discharges from aortic and carotid body chemoreceptor afferents were simultaneously recorded in 18 anesthetized cats to test the hypothesis that aortic chemoreceptors, because of their proximity to the heart, respond to changes in arterial blood gases before carotid chemoreceptors. We found that carotid chemoreceptor responses to the onset of hypoxia and hypercapnia, and to the intravenously administered excitatory drugs (cyanide, nicotine, and doxapram), preceded those of aortic chemoreceptors. Postulating that this unexpected result was due to differences in microcirculation and mass transport, we also investigated their relative speed of responses to changes in arterial blood pressure. The aortic chemoreceptors responded to decreases in arterial blood pressure before the carotid chemoreceptors, supporting the idea that the aortic body has microcirculatory impediments not generally present in the carotid body. These findings strengthened the concept that carotid bodies are more suited for monitoring blood gas changes due to respiration, whereas aortic bodies are for monitoring circulation.

Responses of the heart to stimulation of aortic body chemoreceptors in dogs.

We stimulated the aortic chemoreceptors in dogs that were anesthetized with chloralose and artificially ventilated by perfusing the isolated aortic arch with venous blood. Inotropic responses were determined by measuring the maximum rate of change of left ventricular pressure (dP/dt max) with aortic pressure and heart rate held constant. Stimulation of the aortic chemoreceptors resulted in an average increase in heart rate of 14 +/- 2.0 beats/min (mean +/- SE) from 166 +/- 7.7 beats/min and an increase in dP/dt max of 501 +/- 85 mm Hg/sec from 3508 +/- 154 mm Hg/sec. These changes were statistically significant (P less than 0.001). The afferent pathway of the reflex was shown to be in the vagus nerves and the efferent pathway in the cardiac sympathetic nerves. In some of the dogs, the carotid chemoreceptors were also stimulated. This resulted in decreases in heart rate and dP/dt max of 48 +/- 24 beats/min and 795 +/- 142 mm Hg/sec. Thus we have shown that stimulation of aortic chemoreceptors evokes chronotropic and inotropic responses opposite to those evoked from stimulation of carotid chemoreceptors.

Aortic body chemoreceptor responses to changes in PCO2 and PO2 in the cat.

Responses of aortic chemoreceptor afferents to a range of arterial carbon dioxide tension (Paco2) changes at various levels of arterial oxygen tension (Pao2) were investigated in 18 cats anesthetized with alpha-chloralose and maintained at 38 degrees C. Aortic chemoreceptor activity, end-tidal oxygen pressure, end-tidal carbon dioxide pressure, and arterial blood pressure were continuously monitored. Arterial blood gases were measured in steady states. Single or a few clearly identifiable afferents were studied during changes and steady states of Pao2 and Paco2. All the aortic chemoreceptor afferent discharge rates increased with Paco2 increases from hypercapnia (10-15 Torr) to normocapnia and moderate hypercapnia (30-50 Torr) and with Pao2 decreases from above 400 to 30 Torr. Hypoxia augmented the response to Paco2 most effectively in the range of 10-40 Torr. At any Pao2, the discharge rate reached a plateau with sufficient intensity of hypercapnia. The Paco2 stimulus threshold at a Pao2 of 440 Torr was about 15 Torr, and at a Pao2 of 60 Torr it was 10 Torr. In the transition from hypocapnia to hypercapnia, responses increased gradually, usually without an overshoot. The steady-state responses to Paco2 of the majority of aortic chemoreceptors resembled those of carotid chemoreceptors. The responses of both receptors can be attributed to the same basic type of mechanism.

Reflex stimulation of aortic chemoreceptors and the role of vascular receptors

Impulses were recorded in single afferent fibres of aortic chemoreceptors of cats anaesthetized with chloralose. As expected raising the blood pressure (BP) passively by occluding the abdominal aorta, consistently reduced or abolished the activity of the chemoreceptors. This reduction persisted for as long as the BP remained high. Stimulating the sensory receptors of the small intestines increased the activity of 10 aortic chemoreceptors. The increased activity persisted after bilateral adrenalectomy but it was abolished by blocking the nerves of the mesentery with xylocaine. The increased activity was noteworthy because it occurred in spite of the rise in blood pressure (that always occurred when the intestines were squeezed) which by itself would tend to reduce the activity of the chemoreceptors. It was concluded that stimulating the intestinal receptors produces a reflex increase in the activity of aortic chemoreceptors by causing a reduction of glomeral blood flow through impulses in the sympathetic fibres.

Calcium binding sites in the vesicles of the carotid and aortic body chief cells.

Chief cells of the carotid and aortic body chemoreceptors possess numerous cytoplasmic dense-core vesicles which are known to contain primarily dopamine. Following fixation in solutions containing 50 mM CaCl2, a 20--30 nm electron-dense particle (EDP) is often observed eccentrically located in many of the vesicles. Approximately 44% of the carotid body and 16% of the aortic body vesicles contain an EDP. The EDP probably represents the Ca++ binding site critical to the stimulus-secretion coupling events culminating in exocytosis of these vesicles. The presence of Ca++ in the cytoplasmic vesicles was verified by electron probe X-ray microanalysis.

Carbon dioxide sensitivity of aortic chemoreceptors in the cat

Steady state CO 2 sensitiviy in the aortic chemoreceptors was variable. For 70.3% of the steady state response lines to increasing CO 2 the slope was not significantly different from zero. For 24.3% it was significantly positive and for 5.4% significantly negative. In contrast, in 86.7% of cases the oscillating response to alternate breaths of high and low CO 2 suggested a transient response line which was significantly steeper than the steady state line. Removing CO 2 from a high CO 2 content inspirate for one breath caused a distinct drop in discharge on 83.3% of occasions. The significance of such transient CO 2 sensitivity in the absence of clear steady state sensitivity is discussed.

Anemia as a stimulus to aortic and carotid chemoreceptors in the cat.

In cats anesthetized with alpha-chloralose, the activities of aortic and carotid chemoreceptor nerves were measured during a control period and during anemia where the hematocrit was lowered in steps by dextran-for-blood exchange. With anemia there was a sustained nonlinear increase in firing of aortic chemoreceptors. There was a greater firing of aortic chemoreceptors for a given lowering of hematocrit from an initial low blood hematocrit than for a similar decrease in hematocrit from an initial high blood hematocrit. Tonic carotid chemoreceptor firing was independent of blood hematocrit and was only transiently increased at the time of dextran-for-blood exchange. The lack of effect of anemia on carotid chemoreceptor activity appeared to be due to sympathetic nerve activity. Section of the sympathetic nerves to the carotid chemoreceptors resulted in an increase in carotid chemoreceptor afferent activity during anemia in a manner similar to the increase in aortic chemoreceptor activity.

Carotid and aortic chemoreceptor function in the rat

Carotid and aortic chemoreceptor function was studied in normal Wistar rats. Sodium cyanide, lobeline HCl, and doxapram HCl in the doses of 2-400 mug/kg injected into the external carotid artery stimulated respiration significantly. Injections of the drugs into the ascending aorta produced less effects which were abolished after section of the carotid sinus nerves. The drugs produced a significant increase in the carotid sinus nerve activity but failed to do so in the aortic depressor or recurrent laryngeal nerves. These results indicate that the carotid chemoreceptor function in Wistar rats in normal while functional aortic chemoreceptors are absent in them.

Ventilatory control in peripheral chemoreceptor-denervated ponies during chronic hypoxemia

The present study was designed to provide further insight into the role of the carotid and aortic chemoreceptors in ventilatory (VE) acclimatization during sojourn at altitude. Measurements were made: 1) on 10 ponies near sea level (SL, 740 Torr) under normal conditions, 2) on 6 of these at SL following chemoreceptor denervation (CD), and 3) subsequently on all 10 during 4 days of hypobaric hypoxia (PaO2 = 40-47 Torr). CD resulteo in hypoventilation at SL (deltaPaCO2 = d8 Torr, P less than 0.05), and it prevented hyperventilation normally observed with injection of NaCN and acute exposure to hypoxia (less than 1 h). In contrast, hyperventilation was evident in normal ponies during acute hypoxia (deltaPaCO2 = -6.7 Torr). Ventilation increased in both groups between the 2nd and 8th h of hypoxia (deltaPaCO2 from 1 h = -4 Torr, P less than 0.05). This change, a common characteristic of acclimatization, persisted throughout 4 days of hypoxia in the normal ponies. However, in the CD ponies this change was evident consistently only through the 12th h and after the 44 h hyperventilation was no longer evident. We conclude that the peripheral chemoreceptors are essential in ponies for normal VE acclimatization to this degree of hypoxemia. Two additional findings in CD ponies suggest the presence of a CNS inhibitory influence on the VE control center during chronic hypoxemia. First, acute hyperoxygenation on the 4th day of hypoxemia induced hyperventilation (deltaPaCO2 = -5 Torr, P less than 0.05). Second, again on the 4th day and during hyperoxygenation, VE responsiveness to CO2 and doxapram HCl was greater than at sea level.

Stimulation of the aortic and carotid chemoreceptor drive by low doses of chlorpromazine.

Chlorpromazine (75 mg daily) or placebo was administered, during a week, to 10 healthy students, 23–27 years old, on a double-blind cross-over basis. Minute ventilation and alveolar ventilation increased significantly under Chlorpromazine (p p>0, 05) and increased the arterial PO2 (p<0, 0025), without any change of P-50. We conclude that low oral doses of chlorpromazine had no influence on the alveolar-capillary O2-carriage. The drug taken in the chosen dosis, however, seems to stimulate the aortic and carotid chemoreceptor activity, possibly by a local blockade of the cytochrome P-450.

Effect of stimulation of carotid chemoreceptors on total and regional cerebral blood flow.

This study was performed to determine whether stimulation of the carotid chemoreceptors increases total or regional cerebral blood flow and whether activation of arterial chemoreceptors contributes to cerebral vasodilation during systemic hypoxemia. In anesthetized and ventilated dogs, carotid chemoreceptors were stimulated with nicotine or hypoxic and hypercapnic blood. To measure total and regional cerebral blood flow, we used labeled 15-mu microspheres. Stimulation of chemoreceptors did not increase cerebral blood flow or produce significant redistribution of cerebral blood flow, even though the chemoreflex was intact in these animals (as manifested by vasoconstriction in muscle, kidney, and small bowel) and the cerebral vessels dilated in response to systemic hypercapnia. In other studies in anesthetized, ventilated dogs and rhesus monkeys, cerebral vasodilator responses to systemic hypoxemia were observed before and after denervation of carotid and aortic chemoreceptors. Systemic hypoxemia produced large and equivalent increases in cerebral blood flow before and after chemodenervation. We conclude that stimulation of carotid chemoreceptors does not produce cerebral vasodilation and that chemoreceptors do not contribute significantly to cerebral vasodilation during systemic hypoxemia.

Nonperipheral chemoreceptor stimulation of ventilation by cyanide

To assess the ventilatory responses elicited by changes of tissue hypoxia, sodium cyanide (0.12 mg/kg-min for 10 min) was infused into the upper abdominal aorta of anesthetized dogs. These infusions produced decreases in oxygen consumption, increases in arterial lactate concentration, and increases in arterial lactate/pyruvate ratio. Coincident with these metabolic changes of hypoxia, minute ventilation (VE) increased 228 +/- SE 36% and arterial PCO2 decreased 21 +/- SE 2 mmHg; therefore, pH increased both in arterial blood in and cisternal cerebrospinal fluid. Following infusion of cyanide into the abdominal aorta, small quantities of cyanide (48 +/- SE 14 mumol/liter) appeared in carotid arterial blood. To evaluate the possibility that the observed increases in VE were due to stimulation of peripheral arterial chemoreceptors by the recirculating cyanide, the carotid and aortic chemoreceptors were denervated in four dogs. Nonetheless, after intra-aortic infusion of sodium cyanide (1.2 mg/kg), ventilation in these chemodenervated animals again increased considerably (154 +/- SE 36%). In order to explore the possibility that cyanide infusion can stimulate ventilation by an extracranial mechanism, heads of vagotomized dogs (including the carotid bodies) were perfused entirely by donor dogs. The intra-aortic infusion of sodium cyanide (0.9 mg/kg) into these head-perfused animals still caused large increases in VE (163 +/- SE 19%). It is concluded that intra-aortic cyanide infusions stimulate VE by an extracranial mechanism other than the carotid and aortic chemoreceptors.

The effect of aortic chemoreceptor stimulation on cardiac output and umbilical blood flow in the fetal lamb

Right and left ventricular outputs and umbilical blood flow were studied before and during aortic chemoreceptor stimulation in mature fetal lambs under light chloralose anesthesia. Cardiac outputs were measured by indocyanine green dilution; umbilical blood flow was measured directly with a cannulating electromagnetic flowmeter in the abdominal portion of the umbilical vein. The aortic chemoreceptors were stimulated by minimal doses of sodium cyanide injected into the aortic arch just distal to the coronary ostia. Within 15 to 20 seconds of cyanide injection, left ventricular output rose and right ventricular output fell simultaneously, producing a significant difference between them. Accordingly, the total cardiac (combined ventricular) output was not significantly altered. Within 4 minutes, both left and right ventricular outputs had resumed their resting (preinjection) levels. Aortic chemoreceptor stimulation also produced a significant rise in umbilical blood flow over the same time period. Section of the vagus nerves in the neck abolished all these effects. It is concluded that aortic chemoreceptor stimulation can increase umbilical blood flow in the fetal lamb near term but the effect is chiefly the result of redistribution of an unchanging cardiac output.

The role of the aortic body chemoreceptors in the cardiac and respiratory responses to acute hypoxia in the anesthetized dog.

The participation of the aortic chemoreceptors in the reflex cardiac responses to acute hypoxia is suggested only by the indirect evidence of pharmacological stimulation of these receptors. In order to assess their role more directly, the response to a 15 min period of hypoxia was determined after surgical denervation of the aortic chemoreceptors (A.D.), and compared with the response of sham-operated (S.O.) dogs, anesthetized with morphine–pentobarbital. In the control period, while breathing room air, the cardiovascular and respiratory parameters measured in the A.D. animals were not different from those of the S.O. dogs. Hypoxia (partial pressure of oxygen approximately 30 mm Hg) in the S.O. dogs was associated with a statistically significant rise in the heart rate (+71 ± 7 min−1, mean ± S.E.M.) and of the cardiac output (+25 ± 10 ml kg−1 min−1). In the A.D. animals, the significantly smaller increment in heart rate (+29 ± 6 min−1) was associated with a fall of the cardiac output (−16 ± 12 ml kg−1 min−1). The hypoxia-induced changes in heart rate and cardiac output in the S.O. animals were different (p &lt; 0.05) from those in the A.D. group. The minute volume of ventilation was significantly augmented in both groups, and to a comparable extent. These findings indicate that the aortic chemoreceptors play a significant role in the cardiac response to hypoxia, but they do not affect, to a significant extent, the respiratory response.

Types of afferent nervous activity which may be measured in the vagus nerve of the sheep foetus

1. Afferent activity was measured in the vagus nerves in sixteen foetuses within 2-3 days of natural term and in two foetuses 130 and 135 days gestational age, exteriorized by hysterotomy from seventeen ewes given either a spinal anaesthetic (ten) or pentobarbitone sodium (seven).2. Activity from aortic chemoreceptors was observed which increased in rate with foetal hypoxia, NaCN or nicotine and temporary occlusion of the umbilical cord or veins. Activity was abolished or reduced with saline equilibrated with air.3. Activity from baroreceptors was observed which was synchronous with the arterial pulse and which followed changes in arterial pressure.4. Activity designated as arising from stretch receptors in the lungs or lower airways was observed which consisted of a regular discharge at 15-45 impulses sec(-1), which varied with intra-tracheal pressure, which increased with negative intrathoracic pressure generated by spontaneous respiratory movements, which, when the umbilical cord was occluded, at first increased in rate and then fell to zero at or about the occasion of the first breath. After breathing had been established, activity assumed the rhythmical pattern and showed evidence of slow adaptation of receptors seen in the adult. This activity was frequently modulated by the heart beat and after breathing had started it was reduced when carbon dioxide was raised.5. Respiratory movements with a frequency of 10-20/min occurred spontaneously in foetuses from ewes given a spinal anaesthetic and were associated with a modulation of the stretch receptor discharge. They could be induced by withdrawing fluid from the trachea and so lowering both intra-tracheal pressure and receptor discharge and were abolished by raising intra-tracheal pressure. These changes were abolished by sectioning the vagi just caudal to the nodose ganglion.6. These results indicate that there are excitatory and inhibitory pathways in the vagus nerves which are active in the foetus and which may well be concerned with the limitation of respiratory movements of the foetus and the onset of maintained respiration at birth.

Ventricular responses to hypoxemia following chemoreceptor denervation and adrenalectomy

The sensory system responsible for increased ventricular contractility (VC) during hypoxemia is not fully established. Previous studies have demonstrated that isolated carotid body hypoxia is not associated with an increase of VC. 8 However, reflexly increased VC may result from pharmacologic stimulation of the aortic chemoreceptors. 9 In order to evaluate their contribution during hypoxia, VC was studied in atropinized cats before and following denervation by bilateral vagotomy. VC was measured under conditions of constant aortic pressure, cardiac output, and heart rate. Arterial blood gases and pH were continuously monitored. With hypoxemia (P o 2 27 to 46 mm. Hg), all cats showed an increase of VC, manifested by an increase of dP dt for a given end-diastolic pressure. The responses were unaltered by bilateral vagotomy. Similar findings were obtained in animals with bilateral carotid body denervation. The increase of VC during hypoxia was not significantly less following adrenalectomy. Beta-adrenergic blockade completely abolished these responses. It is concluded that the increase in VC associated with systemic hypoxia cannot be entirely attributed to aortic or carotid chemoreceptor reflex activity. The influence of stimulation of structures within the central nervous system must also be considered.