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PubMed1986

Effects of CO2 and H+ on the ventilatory response to peripheral chemoreceptor stimulation.

To determine whether the stimulatory effect of CO2 on the peripheral chemoreceptors is due to molecular CO2, H+ or both we measured steady-state ventilation (Ve) during normoxia in 9 and during hypoxia in 5 chloralose-urethane anaesthetized cats using the artificial brain stem perfusion technique. This technique allows one to manipulate independently the PaCO2, PaO2 and the pHa of the blood in the systemic circulation (peripheral) and the blood perfusing the brain stem (central). Keeping the central conditions constant the H+ and CO2 concentrations in the systemic circulation were changed by i.v. infusion of 0.3 M HCl or 0.6 M NaHCO3 and by giving the animal different CO2 mixtures to inhale. The peripheral H+ concentration ([H+]p) range covered was from 27 to 103 nmol X 1(-1); the peripheral arterial CO2 tension (PaPCO2) ranged from 2.3 kPa to 8.4 kPa. Fitting the data with the function VE = a[H+]p + bPaPCO2 + c revealed that the coefficient b was not significantly different from zero at the 0.05 level during normoxia and hypoxia. The mean value (+/- SEM) found for the coefficient a was 33.0 +/- 3.6 at normoxia and 36.0 +/- 15.4 ml X min-1 X nM-1 at hypoxia. We conclude that the steady-state ventilatory response due to the stimulation of the peripheral chemoreceptors with CO2 is mediated by H+. The effects of molecular CO2 are negligible.

Acid-Base Equilibrium↗
PubMed1988

Absence of CO2-sensitive venous chemoreceptors in the cat.

We tested for the presence of CO2-sensitive venous chemoreceptors in anesthetized, paralyzed, artificially ventilated cats (N = 8). Systemic venous PCO2 was elevated (venous CO2 loading) by continuously passing blood withdrawn from the femoral artery (20 ml/min) through an extracorporeal gas exchanger, ventilated with 50% CO2 and 50% O2, and returning this hypercapnic blood to the femoral vein. Respiratory output was assessed by means of the amplitude of the integrated phrenic neurogram. Results of venous CO2 loading were compared to those of airway CO2 loading in which inspired CO2 levels were adjusted to give the same arterial PCO2 (PaCO2) as in venous loading. Despite large differences in mixed venous PCO2 (PvCO2) during venous CO2 loading (PvCO2 = 55 Torr, PaCO2 = 37 Torr) compared to airway CO2 loading (PvCO2 = 45 Torr, PaCO2 = 37 Torr), phrenic output was unchanged. However, phrenic output was elevated 33% when PaCO2 was increased 6-7 Torr by raising inspired CO2 and reduced 50% when PaCO2 was lowered 6-7 Torr by lowering inspired CO2, thereby substantiating the responsiveness of the respiratory control system to changes in PaCO2. The respiratory output response to changes in venous CO2 was also tested at a higher PaCO2 (40 Torr, created by adding 1% CO2 to the inspired air) and, as before, no change in phrenic output occurred when PvCO2 was elevated at a constant PaCO2. These experiments provide direct evidence for the absence of chemoreceptors in the central veins, right heart, and pulmonary arterial system of the cat that would respond to changes in PvCO2.

Animals↗
PubMed1988

The relationship between arterial pH and chemoreceptor firing in anaesthetized cats.

The relationship between the respiratory oscillation in arterial pH and resulting respiratory oscillation in afferent chemoreceptor discharge has been investigated in anaesthetized, ventilated cats. The amplitude of the pH oscillations was reduced from a mean of 0.028 pH units to 0.016 by increasing respiratory frequency from 14/min to 20/min. For some chemoreceptors the amplitude of the discharge oscillations was unaffected by this change, whereas for others it was reduced. There was a significant correlation (P less than 0.05) between the reduction in the amplitude of discharge oscillations, caused by increasing respiratory rate, and the delay between the pH oscillation and the corresponding discharge oscillation. The implications of these findings are discussed.

Anesthesia, General↗
PubMed1992

Carotid chemoreceptor response to natural stimuli in the newborn kitten.

The activities of carotid chemoreceptors at three levels of inspired PO2 (55, 145 and 690 Torr) and at two levels of inspired PCO2 (35 and 70 Torr in O2) were studied in 28 anesthetized, mechanically ventilated kittens aged 0-17 days. A biphasic response to hypoxia was found in 46% of them: the chemosensory activity increased to a peak within 30 sec after the initial response to hypoxia and thereafter declined slowly to a stable value. The steady-state single-fiber chemosensory activity at an inspired PO2 of 55 Torr was significantly lower in kittens less than 10 days old (mean +/- SE: 5.8 +/- 0.6 impulses.sec-1) than in the older ones (8.8 +/- 1.3 impulses.sec-1, P less than 0.03). The response curves to arterial PO2 were hyperbolic in both groups but the curve for the younger kittens was displaced to the left of the curve for the older ones. The response to hypercapnia was a progressive increase in chemosensory activity with little evidence of rapid or slow adaptation. The response to hypercapnia was significantly stronger in the older kittens than in the young ones. It is concluded that, in the kitten, the carotid chemoreceptor response to hypoxia may be biphasic. The responses to hypoxia and hypercapnia are already developed but are weak at birth and continue to develop further during the first weeks of postnatal life.

Animals↗
PubMed1993

Temperature and central chemoreceptor drive to ventilation in toad (Bufo paracnemis).

The central chemoreceptor drive to ventilation was assessed in unanesthetized toads, Bufo paracnemis, exposed to three different temperatures: 15, 25 and 35 degrees C. The acid-base status of the fourth ventricle was manipulated by mock CSF perfusion. In additional experiments, arterial pH was varied by inspiration of hypercapnic gas mixtures. Ventilation was measured directly by pneumotachography and arterial blood samples were analyzed using electrodes for pH and PO2. Regardless of temperature, the ventilatory control of acid-base status was predominantly central. Moreover, an increase in temperature was accompanied by a proportional increase in the ventilatory response to chemoreceptor stimulation by either lowered mock CSF pH or hypercapnia. The alphastat hypothesis could not adequately account for the temperature effects on the ventilatory responses to hypercapnia or on air convection requirements in the toad.

Animals↗
PubMed1994

Effect of acute and chronic cobalt administration on carotid body chemoreceptors responses.

Chronic cobalt exposure leads to release and production of erythropoietin and consequently to polycythemia. Accordingly, cellular elements sensitive to oxygen in the carotid body, would manifest responses during acute and chronic cobalt administration. The carotid body, detects gas changes (PO2, PCO2/pH) in the arterial blood and regulates ventilation and circulation by the afferent nerve discharge. We hypothesized that cobalt interacts with an oxygen sensitive mechanism in the carotid chemoreception and in erythropoietin producing cells. Twelve cats were anesthetized, paralysed and artificially ventilated; few fiber preparation of carotid sinus nerve were recorded during close intraarterial injection of cobalt. In another protocol, 12 rats received an intraperitoneal dose of CoCl2 (10 mg/kg) daily for 6 weeks. At the end, the carotid body was fixed in situ by superfusion. Ultrastructural and morphometric studies were made. Acute administration (0.08-2.3 mumol) promptly stimulated the chemoreceptor afferents. Type I cells increased significantly along with erythropoiesis in the chronic cobalt treated rats. The stimulatory effects of cobalt on the carotid body chemoreceptor showed that sensitive mechanisms in the kidney and in the carotid body are similar, and cobalt interacts with the physiological responses of oxygen.

Animals↗
PubMed1981

Cardiovascular control by medullary surface chemoreceptors.

The cardiovascular and respiratory effects of superfusion of the ventral surface of the medulla with acid hypercapnic or alkaline hypocapnic solutions have been studied in anaesthetized, paralyzed, artificially ventilated cats. Peripheral chemoreceptor and baroreceptor denervation was achieved by section of carotid sinus, aortic and cervical vagus nerves. Systemic arterial and central venous pressure, hindquarters blood flow, heart rate and phrenic nerve activity were recorded. Acid hypercapnic (pH 6.8, pCO2 85 mm Hg) superfusion caused increases in systemic arterial pressure, phrenic nerve activity and heart rate, and a decrease in hindquarters blood flow. Alkaline hypocapnic (pH u.i, pCO2 less than 10 mmHg) superfusion caused opposite effects. These experiments indicate a significant role of the chemoreceptors of the ventral surface of the medulla in cardiovascular control.

Animals↗
PubMed1981

Renal chemoreceptors.

A study of the renal receptors and types of stimuli which give origin to supraspinal and spinal-mediated autonomic reflexes is presented. Multiunit and single unit recordings from the afferent renal nerves of male Sprague-Dawley rats have revealed two groups of renal chemosensitive receptors (chemoreceptors). These we have called renal R1 and R2 "chemoceptive" receptors. R1 receptors do not have a resting discharge but are activated after 38.7 +/- 3.3 (S.E) sec (n = 40) of complete renal ischemia (occlusion of the renal artery). Other activating stimuli are associated with a marked impairment in renal blood flow (prolonged occlusion of the renal vein and the hypotension of systemic asphyxia or hemorrhage). Their discharge is characterized by trains of impulses which cease abruptly upon re-entry of blood into the kidney. They are not responsive to increases or decreases in renal perfusion pressure or to increases in renal venous or ureteral pressure. In contrast, R2 receptors have a resting discharge and respond vigorously to backflow of normal urine (nondiuretic) into the renal pelvis. The results of the backflow into the pelvis of different test solutions (diuretic and nondiuretic urine, 1 M urea, 1 M mannitol and solutions of NaCl and KCl) indicate that this response is dependent upon the composition of the fluid bathing the renal pelvis rather than the increase in pelvic pressure or pelvic distension. The resting discharge rate is highest in nondiuretic conditions and declines substantially after diuresis is induced by extracellular volume expansion. R2 receptors are also activated by renal ischemia produced by clamping the renal artery. It is concluded that these two groups of afferent sensory units are renal chemosensitive receptors, (chemoreceptors) which respond to the chemical environment of renal interstitium.

Afferent Pathways↗
PubMed1982

Single-unit and multiunit analyses of renorenal reflexes elicited by stimulation of renal chemoreceptors in the rat.

Stimulation of renal chemoreceptors, induced by backflow of concentrated urine into the renal pelvis, elicited a reflex increase in the rate of multiunit efferent renal nerve activity in rats. Ipsilateral stimulation increased the rate by 17.1 +/- 4.5%; contralateral stimulation increased the rate by 20.8 +/- 4.5%. Efferent activity returned toward control levels within the first minute following removal of the stimulus. The reflex responses were quantitatively similar in rats anesthetized with sodium pentobarbital or alpha-chloralose, but increased following complete transection of the spinal cord at C3. Studies of single efferent units indicated that responses to the stimuli were nonuniform. The majority of single units exhibited an increase in firing frequency during the stimulus; other units showed no change or, less frequently, a reduction in activity during the stimulus. Some postganglionic neurons projecting to the kidney were activated by stimuli applied to either kidney. It was concluded that stimulation of intrarenal chemoreceptors provokes bilateral excitatory renorenal reflexes in the rat. The observation of nonuniform responses among single units suggests that renal nerves contain a mixture of efferent fibers which may contact different targets in the kidney.

Adrenergic Fibers↗
PubMed1987

Involvement of gastrointestinal mechano- and intestinal chemoreceptors in vagal reflexes: an electrophysiological study.

The role of gastrointestinal mechanoreceptors and intestinal chemoreceptors in the genesis of vago-vagal reflexes was assessed by recording single vagal efferent fibre discharge in the urethane-anaesthetized ferret during procedures known to activate discrete populations of gastrointestinal afferent fibres. Distension of the stomach, duodenum and jejunum was used to activate mechanoreceptors while perfusion of the intestinal loops with various chemical solutions was used to activate mucosal chemoreceptors. Mechanical stimulation of the stomach and/or intestine was effective in modulating vagal efferent discharge in 90% of units tested. The response (either excitation or inhibition of efferent firing) was characterized by its short-latency (less than 1 s), slow-adaptation, and rapid return on removal of the stimulus. In contrast, chemical stimulation was much less potent evoking clear-cut responses in only 26 of the 109 efferent units. Luminal HCl was the most effective stimulus accounting for 81% of the efferent responses although these were of long-latency (greater than 1 min), gradual in onset and poorly maintained. Other efferent responses to HCl and hypertonic saline were characterized by a long-latency, sudden increase in discharge associated with the prodrome of vomiting. We conclude that while the mechanosensitive afferent input is well represented in terms of the genesis of vagal reflexes, the chemosensitive afferent input may be more important in behavioural aspects of visceral stimuli like vomiting.

Animals↗
PubMed1987

Reflex responses to baroreceptor, chemoreceptor and nociceptor inputs in single renal sympathetic neurones in the rabbit and the effects of anaesthesia on them.

Reflex responses of renal postganglionic neurones to stimulation of arterial baroreceptors, arterial and central chemoreceptors and cutaneous nociceptors, and the rhythmicity of their resting activity were studied in paralyzed, artificially ventilated rabbits, anaesthetized with either alfathesin or chloralose-urethane. A 'vasoconstrictor' response pattern was seen in all units. Perivascular balloon-induced falls in blood pressure increased firing while pressure rises silenced 90% of units and reduced firing in the rest. Resting activity was linked to pressure changes within the cardiac cycle and to the artificial respiratory cycle. The largest excitation occurred during hypoxia and injections of CO2 saturated solutions into the carotid artery while hypercapnia and stimulation of cutaneous nociceptors only slightly increased firing. Parameters characterizing rhythmicities and reflex responses were unimodally distributed with no apparent subgrouping of units on quantitative grounds. Unit response patterns were similar to those recorded in the whole renal nerve. With one exception, no silent units were found which responded to the afferent inputs studied. Nor was there a small-spike fibre group which was excited by angiotensin. However, reflex responses were significantly influenced by the anaesthetic regime selected for use. Under alfathesin, baroreceptor and chemoreceptor reflexes were double those found with chloralose-urethane. Under chloralose-urethane, hypoxia increased both rhythmicities, while under alfathesin, cardiac rhythmicity was decreased and respiratory rhythmicity was variably affected. We concluded that renal sympathetic neurones are a functionally uniform population which behave like vasoconstrictors.

Action Potentials↗
PubMed1989

Ganglioglomerular nerves influence responsiveness of cat carotid body chemoreceptors to almitrine.

A bolus injection of almitrine bismesylate (0.5 mg.kg-1 i.v.) in anaesthetised artificially ventilated cats caused a significantly greater increase in carotid chemosensory discharge in animals with sectioned ipsilateral ganglioglomerular sympathetic nerves in comparison with a group in which these nerves were intact. Plasma levels of almitrine were similar in both groups. Responses to hypoxia and hypercapnia post-almitrine were also bigger if the ganglioglomerular nerves were cut. Domperidone (10-50 micrograms.kg-1 i.a), a dopamine D2 receptor antagonist, greatly increaed the responsiveness of chemoreceptors to almitrine in ganglioglomerular nerve-intact preparations. Almitrine-induced chemosensory activity was unaffected by illuminating the carotid bifurcation with light from a fibre optic lamp, regardless of whether or not the ganglioglomerular nerves were cut. It is concluded that almitrine may directly or indirectly activate an efferent pathway in the ganglioglomerular nerves to cause depression of chemoreceptor activity, possibly by releasing dopamine to act at D2 dopamine receptors in the carotid body.

Action Potentials↗
PubMed1995

Analysis of carotid chemoreceptor responses to substance P analogue in anaesthetized cats.

Analogues of Substance P (SP) have been shown to act as SP receptor antagonists in various physiological systems. We have previously shown that the carotid body sensory response to hypoxia could be attenuated by D-Pro2-D-Trp7,9-SP (DPDT-SP) and suggested that SP may be important for chemoreception. In the absence of detailed characterization of the antagonistic effects of DPDT-SP, the role of SP in carotid body chemoreception remains uncertain. The present study was undertaken to analyze the effects of DPDT-SP on carotid body activity in anaesthetized cats (n = 18). Intra-carotid infusion of DPDT-SP antagonized SP-induced chemoreceptor stimulation. 90% blockade of SP responses was obtained at infusion rates of 15 micrograms/kg per min of DPDT-SP for 15 min. By contrast, infusions of either saline (controls) or at doses below 10 micrograms/kg per min had no effect on SP responses. The doses that effectively antagonized SP excitation (i.e., 15 micrograms/kg per min) also blocked or markedly attenuated the chemoreceptor responses to hypoxia, without affecting the carotid body stimulation caused by nicotine. The effects of DPDT-SP were associated with significant reduction in baseline activity in normoxia. The antagonistic effects were reversible after terminating the infusion of DPDT-SP. Increasing the dose to 25 micrograms/kg per min, however, abolished the carotid body excitation by any of the stimuli tested (i.e., SP, hypoxia and nicotine), indicating that at higher doses DPDT-SP is non-selective. These results demonstrate that DPDT-SP given in adequate doses to block SP response also attenuates or abolishes the carotid body excitation by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1992

Oxygen and acid chemoreception in the carotid body chemoreceptors.

The carotid bodies are arterial chemoreceptors that are sensitive to blood PO2, PCO2 and pH. They are the origin of reflexes that are crucial for maintaining PCO2 and pH in the internal milieu and for adjusting the O2 supply according to the metabolic needs of the organism in situations of increased demand, such as exercise and while breathing at decreased O2 partial pressures during ascent or when living at high altitude. Chemoreceptor cells of the carotid body transduce the blood-borne stimuli into a neurosecretory response that is dependent on external Ca2+. These cells have an O2-sensitive K+ current that is reversibly inhibited by low PO2. It is proposed that the depolarization produced by inhibition of this K+ current activates Ca2+ channels; Ca2+ influx and neurosecretion follow. The cells have also a potent Na(+)-Ca2+ antiporter that could be responsible for the intracellular Ca2+ rise required to trigger the release of neurotransmitters during high PCO2 or low pH stimulation.

Acids↗
PubMed1980

Substance P as a baro- and chemoreceptor afferent neurotransmitter: immunocytochemical and neurochemical evidence in the rat.

The possibility that substances P (SP) is a neurotransmitter of baro- and chemoreceptor afferents in the rat was investigated. SP-like immunoreactivity (SP-I) was analyzed quantitatively by radioimmunoassay in various levels of the nucleus tractus solitarius (NTS), the site of termination of these afferents while SP-containing afferent neurons were studied in various portions of the peripheral pathways by immunocytochemistry. It was found that the NTS contained significant amounts of SP-I and that unilateral removal of the nodose ganglia reduces the SP-I content of those portions of the NTS known to receive vagal afferents. In addition, SP-I was visualized in discrete fibers in the tunica adventitia of the aortic arch and carotid sinus regions, the vagus nerve and nodose ganglia. These results in the rat are consistent with our previous studies in the cat and provide further evidence that SP is contained within baro- and chemoreceptor afferent nerves.

Afferent Pathways↗
PubMedDate not supplied

Physiological chemoreceptor stimulation decreases enkephalin and substance P in the carotid body.

Neuroactive peptides, including the enkephalins (Met- and Leu-enkephalin; ME, LE) and substance P (SP) are known to be present in the mammalian carotid body, an arterial chemoreceptor organ sensitive to the O2, CO2 and pH levels in blood. The principal parenchymal (type I) cells of the organ, which receive sensory innervation from the carotid sinus nerve (CSN), have been shown to contain both ME and SP; SP is also present in CSN afferent fibers. In the present study, rabbits were exposed in a chamber to a physiological chemoreceptor stimulus (5% O2 in N2) for one hour, then anesthetized during surgical removal of both carotid bodies for later RIA measurement of ME and SP levels in the tissue; control animals were exposed to air in the chamber, but otherwise treated as the hypoxic animals. Both ME and SP levels were significantly reduced (approximately 40%) in the carotid bodies from hypoxic rabbits, compared to their normoxic controls. The results suggest that these neuroactive peptides are released from carotid body elements during physiological stimulation, and consequently may play a role in the transduction of chemosensory information between the type I cells and their apposed afferent terminals.

Anaerobiosis↗
PubMedDate not supplied

Influence of substance P on carotid sinus nerve baro- and chemoreceptor activity in rabbits.

Substance P (SP) is abundant in the carotid sinus nerve (CSN) and has been implicated in baro- and chemoreceptor reflexes. We examined the effect of SP on blood pressure, heart rate, phrenic nerve activity, hindlimb perfusion pressure, and cardiac contractile strength in urethane-anesthetized rabbits with bilaterally cut cervical sympathetic, vagus, and aortic depressor nerves. Retrograde simultaneous injection of SP (0.5-2.7 micrograms/kg in 0.2-0.3 ml saline) into both carotid sinus areas via the internal carotid arteries decreased blood pressure (by 56%), heart rate (by 13%), cardiac contractility (by 25%) and phrenic nerve activity (by 77%). The effect on hindlimb perfusion pressure was variable. There was both a reflex effect and direct hindlimb vasodilation. In another group of rabbits, the carotid sinus areas were vascularly isolated and perfused with SP (0.19 micrograms/min dissolved in Locke's solution) or Locke's solution alone for 5 min. While carotid sinus perfusion pressure was maintained in the range of 80-120 mmHg, mean arterial blood pressure, heart rate, and unit activity from the CSN were recorded. SP increased the activity of 11 of 18 baroreceptor fibers and inhibited all of 20 chemoreceptor fibers. SP decreased mean arterial blood pressure and heart rate, but the changes were less than those obtained with injection of SP into nonisolated carotid sinus arteries because systemic effects of SP, which in some cases counteracted the reflex effects, were eliminated.

Animals↗
PubMed1982

Peripheral synapses in Limulus chemoreceptors.

1. Contact chemoreceptors on spines of Limulus prosomal appendages responded to stimulation by amino acid solutions with slowly adapting activity. 2. Mixtures of amino acids elicited stronger responses than equal concentrations of single amino acids. 3. Single unit responses consisted of irregularly timed, intermittent, bursts of action potentials recorded from the axons of the primary chemoreceptor neurons. 4. These axons send collateral branches to neural plexuses located at points peripheral to the recording sites. 5. Putative chemical synapses among the collaterals are seen and suggested as the site for implementing the second order nature of the responses.

Action Potentials↗