Ventilatory response to sustained hypoxia: effect of methysergide and verapamil

• Published in: Respiration physiology Vol. 75; no. 2; pp. 173 - 182
• Main Authors: Long, G.R., Filuk, R., Balakumar, M., Easton, P.A., Anthonisen, N.R.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.02.1989; Amsterdam Elsevier
• Subjects: Adult; Air breathing; Biological and medical sciences; Calcium Channel Blockers - pharmacology; Clinical Trials as Topic; Double-Blind Method; Female; Fundamental and applied biological sciences. Psychology; Human; Humans; Hypoxia - physiopathology; Hypoxic response; Male; Methysergide; Methysergide - pharmacology; Random Allocation; Respiration - drug effects; Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics; Serotonin; Serotonin Antagonists - pharmacology; Time Factors; Verapamil; Verapamil - pharmacology; Vertebrates: respiratory system; Human; Verapamil; Serotonin; Hypoxic response; Methysergide; Oxygen; Calcium; Neurotransmitter; Hypoxia; Inhibition; Pulmonary ventilation; Respiration; Respiratory system; Inorganic element; Chemoreceptor
• ISSN: 0034-5687
• DOI: 10.1016/0034-5687(89)90061-3

The biphasic nature of the ventilatory response to sustained (30 min) hypoxia may be explained by the central accumulation of a neurochemical with net inhibitory effect or, alternatively, peripheral chemoreceptor adaptation. To determine the role of serotonin (a putative central neuroinhibitor) and calcium ions (a putative peripheral neurotransmitter) in this response we measured V i and breathing pattern during 30 min of sustained isocapnic hypoxia in 11 normal adults 1 h after the double blind administration of either 2 mg methysergide (serotonin antagonist), 80 mg verapamil (calcium channel blocker), or placebo. Each subect was studied once a day for three days. After placebo the mean V i peaked at 12.5 ± 3.4 L/min (176% of resting room air V i). V i then declined to a mean of 9.8± 2.3 L/min (138% of room air V i) during 25 min of constant hypoxia. V i during hypoxia was always greater than V i during room air breathing ( p<0.01), and peak V i during hypoxia was greater than final V i during hypoxia ( p<0.05). The hypoxic response was not significantly affected by either pharmaceutical. At their maximal safe dosage in humans, methysergide and verapamil suggest no role for serotonin and calcium ions. Not excluded is the possibility that drug levels were inadequate to effect meaningful blockade.