Ventilatory response to sustained hypoxia: effect of methysergide and verapamil.
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 VI 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 subject was studied once a day for three days. After placebo the mean VI peaked at 12.5 +/- 3.4 L/min (176% of resting room air VI). VI then declined to a mean of 9.8 +/- 2.3 L/min (138% of room air VI) during 25 min of constant hypoxia. VI during hypoxia was always greater than VI during room air breathing (p less than 0.01), and peak VI during hypoxia was greater than final VI during hypoxia (p less than 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.
Long
G R
GR
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Filuk
R
R
Balakumar
M
M
Easton
P A
PA
Anthonisen
N R
NR
D000328:Adult; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008784:Methysergide / Q000494:pharmacology*; D011897:Random Allocation; D012119:Respiration / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D012702:Serotonin Antagonists; D014700:Verapamil; D008784:Methysergide