title: The peripheral actions of the central neuropeptide somatostatin on control of breathing: effect on metabolic rate and chemoreflex responses in humans.
abstract: 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.
authors.affiliation: Nuffield Department of Anaesthetics, Oxford University Hospitals, Oxford, UK. Electronic address: jaideep.pandit@dpag.ox.ac.uk.
authors.forename: Jaideep J
authors.initials: JJ
authors.lastname: Pandit
authors.affiliation: Nuffield Department of Anaesthetics, Oxford University Hospitals, Oxford, UK.
authors.forename: Harriet
authors.initials: H
authors.lastname: Wordsworth
authors.affiliation: Department of Physiology, Anatomy and Genetics, Oxford, UK.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Little
authors.affiliation: Department of Physiology, Anatomy and Genetics, Oxford, UK.
authors.forename: Federico
authors.initials: F
authors.lastname: Formenti
authors.affiliation: Department of Physiology, Anatomy and Genetics, Oxford, UK.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Robbins
mesh_terms: D000328:Adult; D001481:Basal Metabolism / Q000502:physiology*; D005260:Female; D006728:Hormones / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D006728:Hormones; D013004:Somatostatin
keywords: chemoreflexes; gas exchange; hypercapnia; hypoxia; metabolism; neuropeptides; somatostatin; ventilation; ventilatory control