Local effects of substance P on respiratory regulation in the rat medulla oblongata

1990 ◽  
Vol 68 (2) ◽  
pp. 693-699 ◽  
Author(s):  
Z. B. Chen ◽  
J. Hedner ◽  
T. Hedner
Keyword(s):  
Substance P ◽  
Medulla Oblongata ◽  
Nucleus Tractus Solitarius ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Ventrolateral Medulla ◽  
Response Patterns ◽  
Respiratory Response ◽  
Inspiratory Time ◽  
Ventral Medullary Surface

The effect of substance P (SP) and the SP antagonist [D-Pro2,D-Trp7,9]-SP on basal ventilation was investigated in halothane-anesthetized rats. Microinjections of SP (0.4-1.5 nmol) into the ventrolateral medulla oblongata (VLM), (nuclei gigantocellularis, facialis, ambiguus, and reticularis lateralis) or into the dorsomedial medulla oblongata (DM, nucleus tractus solitarius) and its ventral surroundings dose dependently increased tidal volume (VT) and/or minute ventilation. In sensitive areas, the ventilatory stimulation was initiated within minutes, peaked around 8-10 min, and slowly returned to normal over 30-45 min after the injection. In the VLM sites, the increase in VT was generally accompanied by a decrease in respiratory frequency (f), whereas in the DM, f increased in parallel with VT. Furthermore, within the VLM, the respiratory response patterns differed with the definite location of the SP injection. A shortening of inspiratory time was observed in the ventromedial part, the ventrolateral portion of the nucleus paragigantocellularis and ventral to the nucleus facialis. In contrast, a lengthening of expiratory time was seen when SP was injected or applied more laterally along the ventral portion of nucleus facialis and near or directly on the ventral medullary surface. Application of [D-Pro2, D-Trp7,9]SP before or after SP completely antagonized the excitatory effects of SP on ventilation. The SP antagonist administered into the VLM decreased the ventilatory response to hypoxic breathing but caused no change during hyperoxic conditions.

Substance P in the ventrolateral medulla oblongata regulates ventilatory responses

1990 ◽  
Vol 68 (6) ◽  
pp. 2631-2639 ◽  
Author(s):  
Z. Chen ◽  
J. Hedner ◽  
T. Hedner
Keyword(s):  
Substance P ◽  
Medulla Oblongata ◽  
Nucleus Tractus Solitarius ◽  
Minute Ventilation ◽  
Ventrolateral Medulla ◽  
Cervical Cord ◽  
Co2 Response ◽  
Caudal Region ◽  
Ventilatory Responses ◽  
Cervical Segment

Local injection of substance P (SP) into the ventral portion of the nucleus gigantocellularis, nucleus reticularis lateralis, and nucleus retrofacialis of the ventrolateral medulla oblongata (VLM) or direct application on the ventral surface of the medulla oblongata caused marked stimulation of tidal volume (VT) and/or minute ventilation (VE). The ventilatory response to hypoxia was significantly blunted after SP in the VLM but not in the dorsal medulla oblongata (DM) (nucleus tractus solitarius). The SP antagonist [D-Pro2,D-Trp7,9]SP almost completely inhibited this response when applied locally to a wide area of the superficial layer of the VLM but not of the DM. Unilateral or bilateral application of 0.3-1.5 nmol of the SP antagonist in the VLM (corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment) markedly attenuated the response to a 5% CO2 inhalation. The inhibition of the CO2 response was seen after [D-Pro2,D-Trp7,9]SP in the rostral areas of the medulla oblongata corresponding to the corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment of the cervical cord. Electric somatosensory-induced ventilatory stimulation could be depressed by approximately 70% by [D-Pro2,D-Trp7,9]SP locally applied on the surface of the VLM. We conclude that SP is involved in the hypoxic, hypercapnic, and somatosensory ventilatory responses in the rat. However, these respiratory reflexes are mediated via different neuronal pools in the medulla oblongata, mainly the VLM.

Response to Acute Hypercapnia in the Parents of Victims of Sudden Infant Death Syndrome

PEDIATRICS ◽  
1984 ◽  
Vol 73 (5) ◽  
pp. 652-655
Author(s):  
Jonathan M. Couriel ◽  
Anthony Olinsky
Keyword(s):  
Tidal Volume ◽  
Sudden Infant Death Syndrome ◽  
Infant Death ◽  
Cycle Time ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Sudden Infant Death ◽  
Respiratory Cycle ◽  
Sudden Infant ◽  
Inspiratory Time

The ventilatory response to acute hypercapnia was studied in 68 parents of victims of sudden infant death syndrome and 56 control subjects. Tidal volume, inspiratory time, and total respiratory cycle time were measured before and immediately after a vital capacity breath of 13% CO2 in oxygen. Instantaneous minute ventilation, mean inspiratory flow (tidal volume/inspiratory time), and respiratory timing (inspiratory time/total respiratory cycle time) were calculated. Both groups of subjects showed a marked increase in tidal volume (48.4% ± 26.5%), instantaneous minute ventilation (56% ± 35%), and tidal volume/inspiratory time (56.8% ± 33.5%) after inhalation of the test gas, with little change in inspiratory time/total respiratory cycle time. There were no significant differences between the two groups for ventilation before or after inhalation of the test gas. The ventilatory response to acute hypercapnia is mediated by the peripheral chemoreceptors. These results suggest that an inherited abnormality of peripheral chemoreceptor function is unlikely to be a factor leading to sudden infant death syndrome.

Enkephalin-induced changes in ventilation and ventilatory pattern in adult dogs

1983 ◽  
Vol 55 (4) ◽  
pp. 1311-1320 ◽  
Author(s):  
G. G. Haddad ◽  
M. R. Gandhi ◽  
G. M. Hochwald ◽  
T. L. Lai
Keyword(s):  
Receptor Agonist ◽  
Breathing Pattern ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Periodic Breathing ◽  
Base Line ◽  
Inspiratory Time ◽  
Ventilatory Pattern ◽  
Induced Changes ◽  
Prior Administration

We studied the changes in ventilation induced by intracisternal administration of enkephalins in four unanesthetized adult dogs. Instantaneous minute ventilation (VT/TT) decreased markedly after D-Ala-Met-enkephalinamide (DAME). Mean VT/TT decreased maximally by 20-50 min after DAME and lasted an additional 15-60 min; by 2 h, VT/TT had returned to base line. Four doses (5, 25, 60, and 125 micrograms/kg) of DAME were used, and the ventilatory response depended on the dose. Mean inspiratory time decreased but mean expiratory time and mean TT showed a marked prolongation. Periodic breathing (2-3 breaths separated by long apneic pauses) occurred in every study and the frequency of sighs increased considerably. All these ventilatory changes were reversed by low doses of naloxone or naltrexone; in addition, VT/TT increased well above base line after the administration of these antagonists. However, naloxone did not increase VT/TT when injected without prior administration of DAME. We conclude that 1) the decrease in VT/TT is due to a decrease in respiratory duty cycle; 2) periodic breathing and increased frequency of sighs constitute part of the changes in the ventilatory pattern induced by DAME; 3) a ventilatory withdrawal reaction may occur after a receptor-agonist interaction of short duration; and 4) although enkephalins can modulate ventilation and the breathing pattern in a major way, these data provide no evidence suggesting that this modulation is tonic.

Maturation of ventilatory response to hypoxia in puppies during sleep

1982 ◽  
Vol 52 (2) ◽  
pp. 309-314 ◽  
Author(s):  
G. G. Haddad ◽  
M. R. Gandhi ◽  
R. B. Mellins
Keyword(s):  
Rem Sleep ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Blood Gases ◽  
Inspiratory Time ◽  
Sleep State ◽  
Quiet Sleep ◽  
Steady Level ◽  
The Mean ◽  
Ventilatory Response To Hypoxia

Using the barometric method, we studied the maturation of the ventilatory response to steady-level hypoxia (FIO2 = 15%O2) during sleep in 37 beagle puppies. In rapid-eye-movement (REM) sleep, instantaneous minute ventilation (VT/Ttot) and mean inspiratory time (VT/TI) increased, and inspiratory time (TI) and expiratory time (TE) were shortened in response to hypoxia at all the ages studied (14, 19, 24, 29 days). In quiet sleep, however, VT/Ttot decreased, and TE and Ttot were prolonged at 14 days in response to the same hypoxic stimulus. There was no change in VT/Ttot at 19 and 24 days of age, but VI/Ttot and VT/TI increased, and TI and TE were shortened at 29 days of age in response to hypoxia in the same sleep state. The mean arterial O2 tension (PaO2) dropped during hypoxia to about 45 Torr, and the mean arterial CO2 tension (PaCO2) decreased, and the mean pH increased at all ages in both REM and quiet sleep. We conclude that in beagles puppies 1) the ventilatory response to hypoxia matures at a slower rate in quiet than in REM sleep and depends primarily on timing rather than volume mechanisms: and 2) in response to hypoxia, the regulation of blood gases in REM sleep may be achieved differently from that in quiet sleep in early life.

Postnatal maturation of the respiratory response to O2 in awake newborn lambs

1982 ◽  
Vol 52 (2) ◽  
pp. 428-433 ◽  
Author(s):  
M. A. Bureau ◽  
R. Begin
Keyword(s):  
Tidal Volume ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
The Other ◽  
Respiratory Response ◽  
Occlusion Pressure ◽  
Peripheral Chemoreceptors ◽  
Postnatal Maturation ◽  
Early Change ◽  
Lower Response

The present study was designed to analyze maturation of the respiratory response to hypoxia and hyperoxia in 41 newborn lambs aged 2–90 days. The O2 respiratory response was tested by progressive isocarbic hypoxia while minute ventilation (VE), tidal volume (VT), respiratory frequency (f), mean inspiratory flow (VT/TI), were measured. The occlusion pressure (P0.1) was also determined as an index of the neuromuscular output of the drive to breathe. The strength of the peripheral chemoreceptors was evaluated by the transient O2 100% inhalation test and by the early change in VE (delta VE) to cyanide (KCN) infusion. In all of the 2-, 10-, 30-, and 90-day groups of lambs, hypoxia induced a significant increase in P0.1 and in delta VE, delta VT, f, and VT/TI. The 2-day-old lambs showed a significantly lower response to hypoxia than did the older groups. Similarly, during the hyperoxia test and KCN infusion. Delta VE was smaller in the 2-day lambs than in the other lambs. We conclude that the postnatal maturation of the ventilatory response to O2 occurs in the first 10 days of life in newborn lambs and it is largely due to an increase in sensitivity of the O2 chemoreceptors.

Involvement of ventral medullary surface in respiratory responses induced by 2,4-dinitrophenol

1989 ◽  
Vol 66 (2) ◽  
pp. 598-605 ◽  
Author(s):  
N. R. Prabhakar ◽  
J. Mitra ◽  
E. M. Adams ◽  
N. S. Cherniack
Keyword(s):  
Respiratory Activity ◽  
Minute Ventilation ◽  
Systemic Administration ◽  
Respiratory Response ◽  
Ventral Medullary Surface ◽  
Series Of Experiments ◽  
Focal Cooling ◽  
Spontaneously Breathing ◽  
The Brain ◽  
Respiratory Responses

We examined the contribution of the neural elements near the ventral medullary surface (VMS) to the respiratory response caused by 2,4-dinitrophenol (DNP). Two series of experiments were performed on 12 vagotomized and sinoaortic denervated cats. The first series examined the effect of focal cooling of the VMS on the respiratory response to DNP in four spontaneously breathing, anesthetized cats. When the VMS temperature was 37 degrees C, systemic administration of DNP increased minute ventilation under nearly isocapnic conditions, and focal cooling of the intermediate area of VMS to 20 degrees C attenuated the ventilatory augmentation caused by DNP. To eliminate the influence of anesthetics, a second group of experiments was performed on eight decerebrate, artificially ventilated cats while phrenic nerve activity was monitored as an index of respiration. AgNO3 (10%) was topically applied to the VMS until the respiratory response to inhaled CO2 was abolished. Apnea occurred in seven of eight cats after AgNO3, whereas in the remaining one animal, tidal phrenic activity decreased substantially. Systemic administration of DNP produced no respiratory excitation in any of the animals. On the other hand, rhythmic respiratory activity could be provoked by electrical stimulation of the mesencephalic locomotor area and carotid sinus nerve and by excitation of somatic afferents. Histological examination of the brain stem showed that the AgNO3 had penetrated no more than 350 microns from the ventral medullary surface. These results indicate superficial structures of the VMS are of potential importance in mediating the respiratory responses to hypermetabolism.

Cisternal Na+ transport inhibition and the ventilatory response to CO2

1994 ◽  
Vol 77 (6) ◽  
pp. 2572-2577 ◽  
Author(s):  
M. P. Sullivan ◽  
J. M. Adams
Keyword(s):  
Ion Transport ◽  
Tidal Volume ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Extracellular Fluid ◽  
Ventrolateral Medulla ◽  
Ph Homeostasis ◽  
Transport Inhibition ◽  
Ionic Changes ◽  
End Tidal

When PCO2 rises transiently, glia or neurons may move ions across their cell membranes to restore intracellular pH, in the process changing extracellular pH. Inhibiting ion transport would result in a different extracellular fluid pH (a putative stimulus for the medullary chemoreceptors) and, therefore, in an altered ventilation in response to PCO2. We infused two ion transport inhibitors, amiloride and bumetanide, into the cisterna magna of anesthetized rabbits and compared their ventilatory response to a rebreathing maneuver with sham rabbits receiving no inhibitor. Amiloride (10(-5)-10(-3) M) had no effect; 3 h of 10(-2) M amiloride increased the frequency of breathing and decreased tidal volume but had no net effect on minute ventilation. Bumetanide (10(-3) M) had no effect after 1 h of infusion, but by 3 h it had decreased tidal volume and minute ventilation at 6 and 7% end-tidal CO2 fraction, respectively, during the rebreathe. Three hours of infusion of amiloride and bumetanide did not affect ventilation in a manner consistent with our predictions from previous studies of ionic changes in cerebrospinal fluid. During the 1st h, when neuronal and glial ion transport in the ventrolateral medulla should be inhibited, we found no effect of ion transport inhibition. We conclude that, during the transient hypercapnia of a rebreathing maneuver, Na+/H+ exchange and Na(+)-K(+)-2Cl- cotransport do not play a significant role in immediate rapid pH homeostasis by cellular ion transport in the microenvironment of the medullary chemoreceptors.

Intracisternal DIDS enhances ventilatory response to rebreathing CO2 in rats

1988 ◽  
Vol 65 (4) ◽  
pp. 1611-1616 ◽  
Author(s):  
J. M. Adams ◽  
N. L. Johnson
Keyword(s):  
Heart Rate ◽  
Cerebrospinal Fluid ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Ventral Surface ◽  
Anion Transport ◽  
Disulfonic Acid ◽  
Respiratory Response ◽  
Transport Inhibitor ◽  
Ventilation Response

In 11 anesthetized rats, we tested the hypothesis that carrier-mediated anion transport in part determines the medullary chemoreceptor response to acute hypercapnia by infusing the transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in mock cerebrospinal fluid (CSF) into the cisterna magna. In five additional rats with sham CSF infusion, we found no effect of mock CSF on the response to rebreathing CO2. Dye infused into the cistern stained the putative chemoreceptor areas on the ventral surface of the medulla. DIDS, at 10 to 1,000 nM, increased the respiratory response to CO2 in a dose-related manner but had no effect on arterial pressure or heart rate. At 1,000 nM, the hypercapnic minute ventilation response was almost doubled because of both volume and rate of breathing. We conclude that the net effect of anion transport is to mitigate the stimulus to the medullary chemoreceptors during acute hypercapnia.

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