Carotid Chemoreceptor Discharge Research Articles

Effects of potassium and lactic acid on chemoreceptor discharge in anaesthetized cats

Both increasing [K +]a and falling pHa stimulate ventilation through an action on the peripheral chemoreceptors. We have examined the effect on afferent carotid chemoreceptor discharge, of intravenous infusion of lactic acid alone, KCl alone, and both combined at constant PET CO 2 in anaesthetized, artificially ventilated cats. Infusions of lactic acid alone and KCl alone caused similar increases in both the mean and amplitude of oscillation of chemoreceptor discharge. In the case of the lactic acid alone infusion the increase in the amplitude of oscillation could be accounted for by the resultant increase in carbon dioxide production. Simultaneous infusion of KCl and lactic acid caused an increase in the mean and amplitude of the discharge which was greater than either given alone, although the combined effect was less than additive. The alterations in mean and amplitude of oscillation of discharge during infusion of both agents together may be completely accounted for by a combined effect of increased carbon dioxide production and elevated [K +]a.

Carotid chemoreceptor discharge during epinephrine infusion in anesthetized cats.

It is known that during exercise there is an increase in plasma epinephrine. The purpose of the present investigation was to determine whether stimulation of carotid chemoreceptors by epinephrine is a direct effect or secondary to epinephrine-induced increases in arterial plasma [K+] and whole body CO2 production (VCO2). Chemoreceptor discharge was recorded from single fiber preparations of the carotid sinus nerves in anesthetized cats ventilated to a constant arterial PCO2 (PaCO2). Infusion of epinephrine (1 microgram.kg-1 x min-1) caused arterial [K+] to increase from a mean of 2.7 to 3.8 mM. VCO2 increased so that ventilation had to be increased by 60% to maintain PaCO2 constant. Mean chemoreceptor discharge increased by 50%, but this was no greater than would be predicted on the basis of the increases in arterial [K+] and VCO2. In a further group of experiments epinephrine was infused at 0.1 microgram.kg-1 x min-1 and produced no significant increase in chemoreceptor firing. These experiments provide no evidence for epinephrine having a direct effect on the carotid chemoreceptor.

Effect of adenosine on chemosensory activity of the cat aortic body

Adenosine, which is released during hypoxia, increases carotid chemoreceptor discharge. It is not known if adenosine also may stimulate the aortic chemoreceptors. The purpose of this study was to investigate if adenosine also can stimulate aortic chemoreceptors. The effect of adenosine (0.01, 0.1 and 1.0 μmol/kg) on aortic chemoreceptor discharge was studied in seven anesthetized, paralyzed and artificially ventilated adult cats. Intra-aortic injections of adenosine produced an increased in chemoreceptor discharge, which reached its peak between 10 and 20 s. The chemoreceptor augmentation increased with higher doses of adenosine. Adenosine also caused a fall in blood pressure. The increase of chemoreceptor discharge was not related to fall in arterial blood pressure. Since adenosine is released during hypoxia, it is suggested that part of the cardiovascular changes induced by hypoxia is due to stimulation of aortic chemoreceptors by adenosine.

Effect of adenosine on isolated and superfused cat carotid body activity

Adenosine is known to increase carotid chemoreceptor discharge in vivo. Since adenosine has powerful vascular effects it is possible that this chemoexcitation is indirectly caused by changes in carotid body blood flow. To evaluate this possibility the effect of adenosine (0.02-2.0 mumol) was assessed on the chemoreceptor activity of the cat carotid bodies in vitro. All three doses of adenosine produced an increase in chemoreceptor discharge which reached its maximum within 10-20 s and subsequently returned to preinjection controls within 1 min. The chemoreceptor excitation caused by adenosine was dose-dependent. These results suggest that adenosine induces chemoexcitation without changes in blood pressure and blood flow.

The effect of almitrine bismesylate on the steady-state responses of arterial chemoreceptors to CO 2 and O 2 in the cat

The interaction between almitrine bismesylate, a pharmacological stimulant of peripheral chemo-receptors, and varying levels of oxygen (P O 2 50–600 Torr) and carbon dioxide (P CO 2 10–65 Torr)_on steady state carotid chemoreceptor discharge was investigated in pentobarbitone-anaesthetized cats. Almitrine was given as constant intravenous (50 μg/kg per min for 4 min) and intracarotid infusions (4–16 μg/kg per min) at different levels of alveolar P O 2 ad P CO 2 . Almitrine always excited discharge. The intracarotid infusions at the lower infusion rate (4–8 μg/kg per min) and the i.v. infusions increased the slope of the isoxic response to CO 2. This effect could be reversed by raising P O 2 to high levels. Higher infusion rates of almitrine (16 μg/kg per min) displaced the CO 2 response curve upwards but did not increase its slope above that obtained in control conditions at end-tidal P O 2 of 50 Torr. However, as these higher infusion rates caused levels of discharge greater than those achieved during control conditions, their effects on control CO 2 sensitivity could not be ascertained. Our results suggest that almitrine excites carotid body chemoreceptors by a mechanism similar to that of hypoxia and not like that of carbon dioxide.

Response of the goat carotid body to acute and prolonged hypercapnia

The effect of prolonged hypercapnia on carotid chemoreceptor discharge frequency has not been elucidated. In addition, the effect of acute hypercapnia on chemoreceptor discharge has not been determined in the goat, a species commonly used for ventilatory control studies. Therefore, we determined the effects of acute and prolonged normoxic-hypercapnia on single fiber output of the carotid body of chloralose anesthetized goats. The animals were paralyzed and artificially ventilated. The average acute response curve for 12 single fibers was linear over the range of 30–80 Torr Pa CO2 with a mean slope of 0.115±0.057 (SD) imp·sec −1·Torr −1 Pa CO2. Elevated discharge frequency was maintained during prolonged (up to 240 min, n=11) steady-state hypercapnia ( X ̄ Pa Co2 = 85 Torr) . No systematic time-dependent changes in afferent discharge frequency occurred during the period. The findings obtained during sustained hypercapnia are in contrast to the time-dependent increase in carotid body activity seen previously in our laboratory with prolonged normocapnic-hypoxia of up to 240 min duration.

The effect of hypoxia on the response of the carotid body chemoreceptor to potassium in the anaesthetized cat

The effect of hypoxia on the response of the carotid chemoreceptor to potassium has been investigated in anaesthetized cats. After an initial period of ventilation on air, F I O 2 wad reduced to 0.1–0.13 to give a mean Pa O 2 of 44 mm Hg. KCl was infused intravenously to raise arterial K + to approximately 6 mM and hold it at that level. For 8 experiments in 7 cats, mean chemoreceptor discharge increased from 1.9 impulses · sec −1 on air, to 7.3 impulses · sec −1 during hypoxia to a peak of 12.2 impulses · sec −1 after the first 0.25 min of the potassium infusion. The initial speed of response and pattern of adaptation were similar to those seen in normoxic cats, but the combined effects of hypoxia and hyperleukemia on carotid chemoreceptor discharge were greater than the sum of the individual effects.

Carotid chemoreceptor discharge responses to hypoxia and hypercapnia in normotensive and spontaneously hypertensive rats

The carotid chemoreceptor discharge responses to hypoxia and hypercapnia were quantitatively compared between normotensive (NTR) and spontaneously hypertensive rats (SHR). For this purpose we recorded afferent mass discharges from the carotid sinus nerve (CSN) at various levels of end-tidal O 2 and CO 2 concentrations ( F etO 2 , F etCO 2 (%)) in the urethane-anesthetized, vagotomized and artificially ventilated rats. The CSN chemoreceptor discharge was evaluated by subtracting the small activity remaining in acute hyperoxia (chemoreceptor inactivation), which was estimated as baroreceptor in origin, from the large total CSN activity. The CSN chemoreceptor discharges at various levels of F etO 2 or F etCO 2 were expressed as the percent of control activity measured in normoxic and normocapnic conditions ( F etO 2 , 15−16%; F etCO 2 , 4.5−5.1%). There was an exponential increase in the CSN chemoreceptor discharge as F etO 2 was decreased from hyperoxic to various hypoxic levels (maximally 6%) at a maintained F etCO 2 (normocapnia). The relationship between the CSN chemoreceptor discharge and the hypoxic stimulus was quantitatively assessed by the regression analysis using an exponential function. Exponential increases in the CSN chemoreceptor discharge by hypoxia and the parameters in the exponential function reflecting the sensitivity to hypoxia were significantly higher in the SHR than in the NTR, which indicated a high carotid chemoreceptor discharge response to hypoxia in the SHR. The CSN chemoreceptor discharge was increased linearly by increasing the F etCO 2 from the normocapnic level up to about 10% at a maintained F etO 2 (normoxia). Increases in discharge produced by severe hypercapnia were, however, much smaller than that caused by hypoxia. The slope of the CO 2 stimulus-CSN chemoreceptor discharge response line was almost the same in NTR and SHR. The results demonstrated that the responsiveness of rat carotid chemoreceptor to hypoxia is augmented in the SHR. The role of carotid chemoreceptor afferents in ventilatory reflex responses to hypoxia and their alterations in the SHR are discussed.

The effect of small changes in arterial carbon dioxide tension on carotid chemoreceptor activity in the cat.

The hypothesis that the fluctuations in carotid chemoreceptor discharge represent more than a simple proportional response to respiratory oscillations of Pa, CO2 has been examined. Simultaneous recordings of the activity in few- or multi-fibre chemoreceptor preparations of the cut carotid sinus nerve and oscillations of carotid arterial pH have been made in four anaesthetized cats which were paralysed and artificially ventilated at constant frequency. Chemoreceptor activity was averaged over a minimum of twenty consecutive pH cycles and the amplitude of the fluctuations in discharge frequency determined. Using the mean Pa, CO2 obtained from blood-gas analysis and the slope of the relationship between log Pa, CO2 and pH obtained in each cat, the amplitude of the pH oscillations was converted to Pa, CO2 amplitude. This amplitude relative to the mean Pa, CO2 has been compared with the amplitude of the corresponding fluctuation in the chemoreceptor discharge frequency recorded from the carotid sinus nerve (e.s.n.d. amplitude) relative to its mean level. Whereas the Pa, CO2 amplitude was always less than 8% of the mean Pa, CO2, the c.s.n.d. amplitude ranged from 40 to 186% of the mean discharge frequency. C.s.n.d. amplitude was divided by the corresponding Pa, CO2 amplitude to give an index of the sensitivity of the chemoreceptors to Pa, CO2. This sensitivity has been compared with that determined from the mean discharge frequency produced in response to changes in mean Pa, CO2 comparable in magnitude to the Pa, CO2 amplitude. The former sensitivity was usually at least 3 times greater than the latter. Examination of the fluctuations in chemoreceptor discharge frequency in relation to the corresponding pH oscillations revealed that whereas the minimum discharge frequency coincided with the alkaline peak of the pH oscillation (trough of the Pa, CO2 oscillation), the maximum discharge frequency did not invariably coincide with the acid trough of the pH oscillation (peak of the Pa, CO2 oscillation). On 30% of occasions, the maximum discharge frequency was associated with the region of maximum rate of fall of pH (maximum rate of rise of Pa, CO2). It was concluded that fluctuations in the discharge of carotid chemoreceptors cannot be accounted for on the basis of a simple proportional relationship to Pa, CO2. They contain a large rate of change component.

A high carotid chemoreceptor discharge response to hypoxia in spontaneously hypertensive rat

A high carotid chemoreceptor discharge response to hypoxia in spontaneously hypertensive rat

Breathing pattern of kittens during hypoxia.

In 19 pentobarbital sodium-anesthetized kittens aged 5-34 days, inspired O2 was reduced from 21 to 6-12%. Respiratory frequency (f) and tidal volume (VT) increased within 30 s. Over 5 min f fell to about 60% below control; VT usually fell but remained above control. Arterial pressure fell in 80% of trials, sometimes before f fell. Arterial CO2 was below control, but raising inspired CO2 to keep expired CO2 at control did not prevent the fall in f and VT. The relation between VT and esophageal pressure or diaphragm electromyogram (EMG) did not change consistently, nor was the ratio of high to low frequencies in the diaphragm EMG altered. Carotid chemoreceptor discharge increased within 15 s, and at 5 min it was much above control. We conclude that the change in the breathing pattern in hypoxia is probably due to the activation of a central mechanism.

Ventilation and carotid chemoreceptor discharge during venous CO 2 loading via the gut

A simple method of loading CO 2 into the venous blood of anaesthetized or decerebrate cats is described. Heated humidified gas of high CO 2 content is passed retrogradely through the gut. This increases CO 2 elimination from the lungs by 1.8 to 3.6 fold, minute ventilation by 1.5 to 2.7 fold and cardiac output by 1.1 to 1.6 fold. This method of venous CO 2 loading allows the recording of afferent nerve impulses. We show that it has little effect on the mean discharge frequency of carotid body chemoreceptors when end-tidal gases are held constant, but that it enhances greatly the amplitude of the respiratory oscillation of their discharge.

1253A THE PATTERN OF BREATHING OF KITTENS DURING HYPOXIA

The reduction in (F,I,O2) in preterm infants and in anaesthetized kittens less than 35 days of age produces an increase in ventilation which is not sustained. This has been widely interpreted as respiratory failure. We studied the pattern of breathing during hypoxia in 16, pentobarbitone anaesthetized kittens 5-30 days of age, and have related it to oesophageal pressure, diaphragm (Dia) e.m.g., phrenic activity (PA) carotid chemoreceptor discharge, arterial pressure, expired FCO2 and FO2 PaCO2, PaO2, PHa and rectal temp. F1O2 was reduced from 0.21 to 0.06- 0.12, sometimes adding CO2. Respiratory frequency (f) and tidal volume (VT) was increased within 30 sec. Over 5 min f fell to up to 60% below control and arterial pressure fell in 22 of 43 trials in 9 kittens , sometimes preceding the fall in f. Even when f and VT fell CO2 was always below control. Adding CO2 did not prevent this fall. Hypoxia did not change the relationship between VT and oesophageal pressure or Dia. The ratio of high to low frequencies in the Dia. did not change. PA did not always correlate well with DIA,but this was not altered by hypoxia. Carotid chemoreceptor discharge increased within 15 sec of lowering FI,O2 and at 5 min. it was still much above control. Since the decrease in ventilation was not accompanied by hypercapnia nor muscle fatigue it is not respiratory ‘failure’. A specific central effect modulating breathing pattern must be considered. The Wellcome Trust (Grant 9594/1.5).

Mechanisms of autonomic control of carotid chemoreceptor activity

Single chemoreceptor fibres dissected from the cut carotid sinus nerves of cats were studied when carotid body blood flow was normal, and when it had been abruptly halted by reducing the local perfusion pressure to zero. Ten chemoreceptor fibres which, when normally supplied with blood, increased their discharge by at least 25% in response to sympathetic stimulation, and 7 fibres which, when normally supplied with blood, decreased their discharge by at least 10% in response to carotid sinus nerve stimulation, were chosen for study. The development of discharge during the period of stagnant asphyxia following stoppage of flow was reproducible in repeated control trials for each fibre investigated. Neither sympathetic nor carotid sinus nerve stimulation, commencing at the stoppage of flow and continued throughout the period of asphyxia, produced any significant alteration from the control pattern of developing chemoreceptor discharge. These experiments provide evidence that the effects of sympathetic and carotid sinus nerve stimulation on carotid chemoreceptor discharge are mediated through alterations in carotid body blood flow. When there is no flow there are no effects on discharge.

Evidence for Adrenergic Transmission of the Carotid Chemoreceptor Impulses in the Toad

RECENTLY when recording afferent impulse activity in the nerve supplying the carotid labyrinth in the toad, we have found chemoreceptor fibres which show increased discharge in response to hypoxia just as do those of the mammalian carotid body1. Although acetylcholine has been proposed as the normal chemical transmitter of the mammalian glomus nerve-endings2–8 the evidence is not as yet wholly conclusive. Indeed, electron microscopy has revealed that the mammalian glomus epithelioid cells show numerous catecholamine-containing granules and the opinion has been advanced that the catecholamine may be the transmitter substance3. There is little physiological evidence for this, however, and even noradrenaline itself does not stimulate chemoreceptor discharge6. Based on the standpoint that the adrenaline-like substance produced in the body is not necessarily solely identifiable with noradrenaline, we have tried to stimulate carotid chemoreceptor discharge by electrical excitation of the cardiac sympathetic fibres. Our results indicate that an adrenergic mechanism is responsible for chemosensory transmission.