Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of a 90-min infusion of somatostatin (1 mg/h) on ventilation and the ventilatory responses to hypoxia and hypercapnia were studied in six normal adult males. Minute ventilation (VE) was measured with inductance plethysmography, arterial 02 saturation (SaO2) was measured with ear oximetry, and arterial PCO2 (Paco2) was estimated with a transcutaneous CO2 electrode. The steady-state ventilatory response to hypoxia (delta VE/delta SaO2) was measured in subjects breathing 10.5% O2 in an open circuit while isocapnia was maintained by the addition of CO2. The hypercapnic response (delta VE/delta PaCO2) was measured in subjects breathing first 5% and then 7.5% CO2 (in 52-55% O2). Somatostatin greatly attenuated the hypoxic response (control mean -790 ml x min-1.%SaO2 -1, somatostatin mean -120 ml x min-1.%SaO2 -1; P less than 0.01), caused a small fall in resting ventilation (mean % fall - 11%), but did not affect the hypercapnic response. In three of the subjects progressive ventilatory responses (using rebreathing techniques, dry gas meter, and end-tidal Pco2 analysis) and overall metabolism were measured. Somatostatin caused similar changes (mean fall in hypoxic response -73%; no change in hypercapnic response) and did not alter overall O2 consumption nor CO2 production. These results show an hitherto-unsuspected inhibitory potential of this neuropeptide on the control of breathing; the sparing of the hypercapnic response is suggestive of an action on the carotid body but does not exclude a central effect.
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PMID:Somatostatin inhibits the ventilatory response to hypoxia in humans. 287 50

In seven normal subjects the ventilatory responses to progressive isocapnic hypoxia and hyperoxic hypercapnia were measured during rebreathing. During an infusion of somatostatin (10 nmol/min) the mean hypoxic response decreased by 66% (control: -1.6 SD 1.2 litres min-1 %-1 SaO2; somatostatin: -0.6 SD 0.7) but the mean hypercapnic response was unchanged (control: 2.0 SD 0.8 litre min-1 mmHg-1; somatostatin: 2.3 SD 1.2). There was no change in resting VO2 or VCO2 during somatostatin infusion. The opiate antagonist, naloxone (0.1 mg/kg, intravenously), caused little change in either response (mean hypoxic response: -1.7 SD 1.0 litre min-1 %-1 SaO2; mean hypercapnic response: 2.4 SD 0.9 litre min-1 mmHg-1). In five of the subjects the dopamine antagonist, prochlorperazine (10 mg, intravenously), increased the mean hypoxic response by 134% (control: -1.9 SD 1.4 litres min-1 %-1 SaO2; after prochlorperazine: -3.8 SD 1.6; P less than 0.05). The mean hypercapnic response after this drug was also increased (control: 2.1 SD 1.0 litre min-1 mmHg-1; after prochlorperazine: 3.1 SD 1.0) but this change did not achieve significance. The selective effect of somatostatin on the hypoxic response, suggestive of an action on the carotid body, was not inhibited by prior injection of either naloxone or prochlorperazine, and its mode of action remains to be found.
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PMID:Effects of somatostatin, naloxone and prochlorperazine on the control of ventilation in man. 287 60

Concentrations of H+ and HCO3- rise in fluid lining hypercapnic airways. Effects of these ions on pulmonary endocrine cells were studied in 119 fetal rat lung organ cultures by semiquantitative staining for calcitonin gene-related peptide (CGRP)-like immunoreactive material. Intracellular CGRP was determined in cultures under "no-release" baseline conditions and after incubation in control or test media. After exposure to HCO3(-)-free medium at pH 7.4 (incubation control), CGRP fell moderately from no-release levels. Bombesin (1 ng/ml) promoted further significant loss of peptide, which was dependent on extracellular Ca2+ and inhibited by somatostatin and [D-Arg(1),D-Pro(2),D-Trp(7,9),Leu(11)]substance P, a bombesin receptor antagonist. CGRP staining of explants incubated with 24 mM HCO3- maintained no-release levels at and above pH 7.1 but decreased significantly at pH 6.8. The drop was blocked by somatostatin or exclusion of HCO3- and was not augmented by bombesin or 48 mM HCO3-. Results suggest that pulmonary endocrine cells may respond to hypercapnia by releasing bioactive peptides like CGRP, thus stimulating afferent nerves and altering patterns of ventilation and perfusion.
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PMID:Effects of hydrogen and bicarbonate ions on endocrine cells in fetal rat lung organ cultures. 912 67

1. Somatostatin depresses the ventilatory response to hypoxia (AHVR). This study sought to determine whether somatostatin also reduced the peripheral chemoreflex sensitivity to hypercapnia, and if so, whether this was related to the reduction in AHVR. 2. Nine subjects completed the study. AHVR and the ventilatory responses to hypercapnia under both hyperoxic and hypoxic conditions were assessed both without and with an infusion of somatostatin (0.5 BsBs5mgBs5 h-1). Peripheral (fast) and central (slow) responses to hypercapnia were distingushed by use of a multi-frequency binary sequence input in end-tidal PCO2 (PET,CO2) that included 13 steps into and out of hypercapnia. 3. The acute ventilatory response to a reduction in end-tidal PO2 (PET,O2) from 100 to 50 Torr (at a PET, CO2 of +1.5-2.0 Torr above normal) was reduced from (mean +/- s.e.m. ) 16.4 +/- 3.3 to 9.5 +/- 3.2 l min-1 (P < 0.005, Student's t test) by somatostatin. The magnitude of the ensuing hypoxic ventilatory decline was unaltered (8.8 +/- 2.7 l min-1 in control vs. 8.0 +/- 2. 9 l min-1 with somatostatin). 4. The peripheral chemoreflex sensitivity to CO2 in hypoxia was reduced from 2.42 +/- 0.36 to 1.18 +/- 0.20 l min-1 Torr-1 (P < 0.005) with somatostatin. The reduction under hyperoxic conditions from 0.75 +/- 0.34 to 0.49 +/- 0.09 l min-1 Torr-1 did not reach significance. Central chemoreflex sensitivity to CO2 was unchanged. Changes in peripheral chemoreflex sensitivity to CO2 in hypoxia correlated with changes in AHVR. 5. We conclude that peripheral chemoreflex sensitivity to CO2 is reduced by somatostatin, probably via the same mechanism as that by which somatostatin exerts its effects on AHVR.
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PMID:Effects of somatostatin on the control of breathing in humans. 1056 52

Peripherally infused somatostatin in humans reduces the acute ventilatory response to hypoxia but it is not known if it reduces basal minute ventilation, and there are conflicting results as to whether or not it reduces the acute hypercapnic ventilatory response. One explanatory mechanism for all these possible effects is that somatostatin reduces metabolic rate. We therefore tested the hypothesis that somatostatin can reduce whole-body metabolic rate (measured by gas exchange at the mouth) in a manner that (a) reduces basal minute ventilation, (b) reduces ventilatory response to acute hypoxia, and (c) reduces ventilatory response to acute hypercapnia. Seven healthy volunteers underwent two protocols, one with saline control and one with somatostatin infusion (0.5mg/h) consisting of a 15-min period of resting breathing (end-tidal [Formula: see text] held at 100Torr with background isocapnia) followed by 5min of isocapnic hypoxia (end-tidal [Formula: see text] 50Torr), and after 1min euoxic recovery, 5min of euoxic hypercapnia (end-tidal [Formula: see text] 45Torr), followed by recovery. Somatostatin modestly but significantly (p<0.05) reduced CO2 output, but not O2 uptake. However, somatostatin did not change basal minute ventilation. Acute hypoxic ventilatory response was greatly reduced by 82% and acute hypercapnic ventilatory response by 26% (p<0.05). We conclude that while somatostatin does influence metabolism, this effect is too subtle to explain the large reduction in chemoreflex activity, which is more likely due to direct effects of the drug on the carotid body.
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PMID:The peripheral actions of the central neuropeptide somatostatin on control of breathing: effect on metabolic rate and chemoreflex responses in humans. 2474 56