[Ventilatory mechanical analysis of respiratory depression induced by serotonin].
This study was aimed to prove the pharmacological characteristics of 5-hydroxytryptamine (5-HT)-induced respiratory depression, especially apnea. Effects of 5-HT-receptor agonists and antagonists on respiratory parameters were examined using anesthetized and spontaneously breathing rats. A bolus intravenous administration of 5-HT (3.125-25 micrograms/kg) immediately produced an apnea, the duration of which increased in a dose-related manner. This response was antagonized by a selective 5-HT3-receptor antagonist, GR38032F (10 and 100 micrograms/kg). Ketanserin, a 5-HT2-receptor antagonist, 100 micrograms/kg also inhibited the 5-HT-induced apnea. In addition, the effect of 5-HT-induced apnea mimicked by 2-methyl-5-HT (3.125-50 micrograms/kg), a 5-HT3-receptor agonist, and by alpha-methyl-5-HT (3.125-25 micrograms/kg), a 5-HT2-receptor agonist. On the other hand, 5-HT produced a decrease in lung compliance and an increase in lung resistance in a dose-related manner. The 5-HT-induced changes in lung compliance and lung resistance were antagonized by ketanserin (100 micrograms/kg), but not by GR38032F (100 micrograms/kg). Furthermore, alpha-methyl-5-HT caused bronchoconstriction as did 5-HT, but 2-methyl-5-HT did not. Although bilateral vagotomy at the supra-nodose ganglia completely prevented 5-HT-induced apnea, cervical vagotomy below the superior laryngeal nerve did not prevent this change. On the other hand, cervical vagotomy almost prevented bronchoconstrictive responses, and completely blocked alpha-methyl-5-HT-induced apnea. These results suggest that 5-HT-induced apnea might be mediated through 5-HT3-receptor mechanisms of the vagal afferent system including the nodose ganglia, and that 5-HT2-receptor mechanisms also contribute to the apnea via the afferent cervical vagus nerves. Direct and indirect bronchoconstriction might also be partly involved in 5-HT-induced apnea.
Goda
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Department of Anesthesiology, Hokkaido University School of Medicine, Sapporo, Japan.
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001049:Apnea / Q000139:chemically induced / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007650:Ketanserin / Q000494:pharmacology; D008170:Lung Compliance / Q000187:drug effects*; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D014628:Vagotomy
D011985:Receptors, Serotonin; D012701:Serotonin; D017294:Ondansetron; D007650:Ketanserin