Dopaminergic efferent inhibition of carotid body chemoreceptors in chronically hypoxic cats

The observations that the dopamine concentration of the carotid body and efferent inhibition of carotid chemoreceptors are increased during chronic hypoxia led to the hypothesis that the inhibition was due to the effect of an increased dopamine release by the activity of carotid sinus nerve (CSN) efferents. The hypothesis was tested by measuring the effect of dopamine receptor blockade on efferent inhibition of carotid chemosensory responses to graded levels of arterial O2 partial pressure in chronically hypoxic and normoxic cats. Chronically hypoxic cats were prepared by exposing the cats to 10% O2 at sea level for 30–34 days. Carotid chemosensory activity was first measured from a slip of an otherwise intact CSN. The measurements were then repeated after sectioning the remaining nerve trunk. The effect of sectioning the CSN provided the measure of efferent inhibition. In each group of cats the effects of sectioning the CSN with and without dopamine receptor blockade by haloperidol were also studied. CSN section augmented the chemosensory responses in the chronically hypoxic cats. Haloperidol, a dopamine antagonist, augmented the responses further, indicating that a part of the endogenous dopamine effect was independent of the CSN efferents. After haloperidol treatment CSN section did not influence the chemosensory responses. This study confirmed that the efferent inhibition significantly increased in the chronically hypoxic cats and demonstrated that haloperidol blocked the efferent inhibition, suggesting that the mechanism of the augmented inhibition is dopaminergic.

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

The Journal of Physiology ◽

10.1113/jphysiol.1974.sp010484 ◽

1974 ◽

Vol 237 (2) ◽

pp. 315-340 ◽

Cited By ~ 114

Author(s):

J. Ponte ◽

M. J. Purves

Keyword(s):

Blood Vessels ◽

Carotid Body ◽

Carotid Sinus ◽

Cerebral Blood Vessels ◽

Carotid Body Chemoreceptors

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Contribution of the carotid body chemoreceptors to eupneic ventilation in the intact, unanesthetized dog

Journal of Applied Physiology ◽

10.1152/japplphysiol.91590.2008 ◽

2009 ◽

Vol 106 (5) ◽

pp. 1564-1573 ◽

Cited By ~ 48

Author(s):

Grégory M. Blain ◽

Curtis A. Smith ◽

Kathleen S. Henderson ◽

Jerome A. Dempsey

Keyword(s):

Steady State ◽

Carotid Body ◽

Sensory Input ◽

Carotid Sinus ◽

Respiratory Acidosis ◽

Tonic Activity ◽

Inspiratory Flow Rate ◽

Compensatory Response ◽

Per Se ◽

Carotid Body Chemoreceptors

We used extracorporeal perfusion of the reversibly isolated carotid sinus region to determine the effects of specific carotid body (CB) chemoreceptor inhibition on eupneic ventilation (V̇i) in the resting, awake, intact dog. Four female spayed dogs were studied during wakefulness when CB was perfused with 1) normoxic, normocapnic blood; and 2) hyperoxic (>500 mmHg), hypocapnic (∼20 mmHg) blood to maximally inhibit the CB tonic activity. We found that CB perfusion per se (normoxic-normocapnic) had no effect on V̇i. CB inhibition caused marked reductions in V̇i (−60%, range 49–80%) and inspiratory flow rate (−58%, range 44–87%) 24–41 s following the onset of CB perfusion. Thereafter, a partial compensatory response was observed, and a steady state in V̇i was reached after 50–76 s following the onset of CB perfusion. This steady-state tidal volume-mediated hypoventilation (∼31%) coincided with a significant reduction in mean diaphragm electromyogram (−24%) and increase in mean arterial pressure (+12 mmHg), which persisted for 7–25 min until CB perfusion was stopped, despite a substantial increase in CO2 retention (+9 Torr, arterial Pco2) and systemic respiratory acidosis. We interpret these data to mean that CB chemoreceptors contribute more than one-half to the total eupneic drive to breathe in the normoxic, intact, awake animal. We speculate that this CB contribution consists of both the normal tonic sensory input from the CB chemoreceptors to medullary respiratory controllers, as well as a strong modulatory effect on central chemoreceptor responsiveness to CO2.

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Mechanism of efferent inhibition of carotid body chemoreceptors in the cat

Brain Research ◽

10.1016/0006-8993(72)90236-3 ◽

1972 ◽

Vol 45 (1) ◽

pp. 266-270 ◽

Cited By ~ 46

Author(s):

S.R. Sampson

Keyword(s):

Carotid Body ◽

Efferent Inhibition ◽

Carotid Body Chemoreceptors

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Effect of dopamine on hypoxic ventilatory response of sedated piglets with intact and denervated carotid bodies

Journal of Applied Physiology ◽

10.1152/jappl.1994.77.1.285 ◽

1994 ◽

Vol 77 (1) ◽

pp. 285-289 ◽

Cited By ~ 10

Author(s):

C. Suguihara ◽

D. Hehre ◽

E. Bancalari

Keyword(s):

Blood Pressure ◽

Arterial Blood Pressure ◽

Carotid Body ◽

Minute Ventilation ◽

Initial Increase ◽

Dopamine Antagonist ◽

Drug Infusion ◽

Endogenous Dopamine ◽

Arterial Blood ◽

Carotid Bodies

To determine whether the neonatal hypoxic ventilatory depression is in part produced by an increased endogenous dopamine release that can depress the activity of central and peripheral chemoreceptors, 31 sedated and spontaneously breathing newborn piglets [age 5 +/- 1 (SD) days; weight 1.7 +/- 0.4 kg] were randomly assigned to an intact carotid body or a chemodenervated group. Minute ventilation (VE), arterial blood pressure, and cardiac output (CO) were measured in room air before infusion of saline or the dopamine antagonist flupentixol (0.2 mg/kg i.v.) and 15 min after drug infusion and were repeated after 10 min of hypoxia (inspiratory O2 fraction = 0.10). VE increased significantly after 10 min of hypoxia in the piglets that received flupentixol independent of whether the carotid bodies were intact or denervated. However, the increase in VE was largest and sustained throughout the 10 min of hypoxia only in the intact carotid body flupentixol group. As expected, the initial increase in VE with hypoxia was abolished by carotid body denervation. Changes in arterial blood gases, CO, and mean arterial blood pressure with hypoxia were not different among groups. These results demonstrate that flupentixol reverses the late hypoxic decrease in VE, acting through peripheral and central dopamine receptors. This effect is not related to changes in cardiovascular function or acid-base status.

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Analysis of inhibitory effect of dopamine on carotid body chemoreceptors in cats

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1976.230.6.1494 ◽

1976 ◽

Vol 230 (6) ◽

pp. 1494-1498 ◽

Cited By ~ 26

Author(s):

SR Sampson ◽

MJ Aminoff ◽

RA Jaffe ◽

EH Vidruk

Keyword(s):

Blood Flow ◽

Carotid Body ◽

Carotid Sinus ◽

Direct Action ◽

Inhibitory Effect ◽

Gas Mixture ◽

Carotid Sinus Nerve ◽

Perfusion Pump ◽

Flow Through ◽

Carotid Body Chemoreceptors

The inhibitory effect of dopamine on carotid body chemoreceptors was studied in anesthetized cats to determine whether it was dependent on changes in blood flow in the vicinity of the receptors. The blood supply to the carotid body was isolated, and flow was controlled with a perfusion pump. Single- or few-fiber recordings were made from the peripheral end of the cut carotid sinus nerve in seven cats. The rate of discharge of 68 chemoreceptor strands increased when flow through the carotid body was stopped. This response was reduced or abolished by dopamine in animals ventilated with either room air (15 strands) or a gas mixture of 95% O2 and 5% CO2 (53 strands). These results suggest that dopamine exerts its inhibitory effect primarily through a direct action on the chemoreceptors rather than by a vasomotor effect in the carotid body.

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Effect of prolonged dopamine receptor blockade on lactotroph activity in the rat pituitary gland

Acta Endocrinologica ◽

10.1530/acta.0.1100469 ◽

1985 ◽

Vol 110 (4) ◽

pp. 469-474 ◽

Cited By ~ 4

Author(s):

R. A. Prysor-Jones ◽

J.J. Silverlight ◽

J. S. Jenkins

Keyword(s):

Dopamine Receptor ◽

Inhibitory Action ◽

Hormone Secretion ◽

Secretory Activity ◽

Dopamine Antagonist ◽

Dopamine Turnover ◽

Receptor Blockade ◽

Pituitary Tumours ◽

Dopamine Content ◽

Rat Pituitary

Abstract. The dopamine antagonist fluphenazine was administered to young rats in the presence or absence of physiological concentrations of oestradiol for periods of 230 days. An important observation arising from the investigation was that no pituitary tumours were produced by the combination of prolonged dopamine receptor blockade and small amounts of oestradiol. Prolactin (Prl) secretion increased rapidly with fluphenazine but in the absence of oestrogen lactotroph activity subsequently declined after 20 days and this decrease in hormone secretion was accompanied by a greatly increased dopamine turnover in the medio-basal hypothalamus. In contrast, small amounts of oestradiol modified the effect of fluphenazine alone causing a greatly increased secretion of Prl for a much larger period and a reduction in the dopamine content of the hypothalamus. This combination also doubled the synthesis of DNA by the pituitary compared with controls, and electron microscopy revealed evidence of increased secretory activity of the lactotrophs in the presence of both fluphenazine and oestrogen but not in those animals treated with fluphenazine only. Towards the end of the experiment Prl values declined even in the presence of oestrogen and increasing the dose of fluphenazine had no significant effect. It was suggested that eventually there may be a direct inhibitory action of the dopamine antagonist on the lactotrophs.

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Arterial chemoreceptor input to nucleus tractus solitarius

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.263.2.r368 ◽

1992 ◽

Vol 263 (2) ◽

pp. R368-R375 ◽

Cited By ~ 46

Author(s):

S. W. Mifflin

Keyword(s):

Carotid Body ◽

Carotid Sinus ◽

Nucleus Tractus Solitarius ◽

Excitatory Input ◽

Inhibitory Input ◽

Mechanically Ventilated ◽

The Central Nervous System ◽

Carotid Body Chemoreceptors ◽

Two Peaks ◽

Arterial Chemoreceptor

The arterial chemoreceptors play an important role in the reflex regulation of blood pressure and respiration. To investigate the initial integration of chemoreceptor inputs within the central nervous system, intracellular recordings were obtained in pentobarbital-anesthetized, paralyzed, and mechanically ventilated cats, from 58 cells within the nucleus of the tractus solitarius (NTS) that were depolarized by activation of the ipsilateral carotid body chemoreceptors. Close arterial injection of less than 100 microliters CO2-saturated bicarbonate evoked depolarizations of membrane potential with amplitudes of 2.2-4.6 mV and durations of 1.8-6.7 s in 46 cells. In 12 cells, activation of the carotid body chemoreceptors evoked a depolarization-hyperpolarization sequence. Electrical stimulation of the carotid sinus nerve (500 microA, 0.2 ms) evoked EPSPs [mean latency 6.4 +/- 0.5 (SE) ms; range 2.1-18.4 ms] in 46 cells and EPSP-IPSPs (7.3 +/- 0.8 ms; range 4.2-12.4 ms) in 12 cells. The distribution of EPSP latencies exhibited two peaks, one in the 2- to 4-ms range and another in the 7- to 8-ms range. Twenty-nine chemoreceptive cells were tested for the presence of convergent inputs from the ipsilateral carotid sinus baroreceptors. No evidence was found of a convergent postsynaptic inhibitory input from the baroreceptors within the NTS; however, seven cells were found that received an excitatory input from the baroreceptors. The observation that NTS neurons do not integrate chemoreceptor afferent inputs in a homogeneous manner suggests that the multiplicity of NTS unit responses might be related to the specific reflex function of an individual cell (e.g., vagal or sympathetic outflow, respiration).(ABSTRACT TRUNCATED AT 250 WORDS)

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Separation of carotid body chemoreceptor responses to O2 and CO2 by oligomycin and by antimycin A

AJP Cell Physiology ◽

10.1152/ajpcell.1982.242.3.c200 ◽

1982 ◽

Vol 242 (3) ◽

pp. C200-C206 ◽

Cited By ~ 61

Author(s):

E. Mulligan ◽

S. Lahiri

Keyword(s):

Steady State ◽

Carbonic Anhydrase ◽

Partial Pressure ◽

Carotid Body ◽

Body Tissue ◽

Antimycin A ◽

Tissue Ph ◽

Co2 Partial Pressure ◽

O2 Partial Pressure ◽

Metabolic Hypothesis

The cat carotid chemoreceptor O2 and CO2 responses can be separated by oligomycin and by antimycin A. Both of these agents greatly diminish or abolish the chemoreceptor O2 response but not the nicotine or CO2 responses. After either oligomycin or antimycin, the responses to increases and decreases in arterial CO2 partial pressure (PaCO2) consisted of increases and decreases in activity characterized respectively by exaggerated overshoots and undershoots. These were eliminated by the carbonic anhydrase inhibitor, acetazolamide, suggesting that they resulted from changes in carotid body tissue pH. The steady-state PaCO2 response remaining after oligomycin was no longer dependent on arterial O2 partial pressure (PaO2). All effects of antimycin were readily reversible in about 20 min. The separation of the responses to O2 and CO2 indicates that there may be at least partially separate pathways of chemoreception for these two stimuli. The similarity of the oligomycin and antimycin results supports the metabolic hypothesis of chemoreception.

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