Effects of serotonin receptor blockade by methysergide on loaded breathing in the rabbit.
Previous works demonstrated that the excitatory role of serotonin (5-hydroxytryptamine, 5-HT) on ventilation is mediated by 5-HT1,2 receptors stimulation. We hypothesized that load-induced hypoventilation could be minimized by a central release of 5-HT. Conversely, blockade of 5-HT receptors should accentuate hypoventilation. We compared the ventilatory effects of methysergide (MS), a 5-HT1,2 receptors antagonist, in 3 groups of anesthetized, spontaneously breathing rabbits: (1) a group of animals breathing for 60 min through a 370 cm H2O.liter-1.s inspiratory resistive load (IRL group), whose paCO2 increased with IRL; (2) a Control group; (3) a Control + CO2 group, made hypercapnic to assess the possible effect of this stimulus on the ventilatory responses to MS. In the 3 groups, i.v. injection of MS induced the same ventilatory changes, characterized by a rapid shallow breathing with a shorter integrated diaphragmatic activity. This confirms the tonic facilitatory effect of 5-HT on ventilation and suggests that IRL would not increase 5-HT release in the sites close to the respiratory nuclei.
Delpierre
S
S
Laboratoire de Physiologie Respiratoire, Faculté de Médecine Timone, Marseille, France.
Duté
N
N
Jammes
Y
Y
D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D008784:Methysergide / Q000494:pharmacology*; D011817:Rabbits; D012125:Respiratory Center / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013990:Tidal Volume / Q000187:drug effects
D012702:Serotonin Antagonists; D008784:Methysergide