Time-dependent hypoxic ventilatory responses in rats: effects of ketanserin and 5-carboxamidotryptamine

We hypothesized that the 5-hydroxytryptamine (5-HT) active drugs ketanserin and 5-carboxamidotryptamine (5-CT) would modulate time-dependent hypoxic p hrenic and hypoglossal responses, including 1) short-term hypoxic response, 2) posthypoxia frequency decline (PHFD), and 3) long-term facilitation (LT F) of respiratory motor output. Phrenic and hypoglossal nerve activities we re recorded in urethan-anesthetized, paralyzed, vagotomized, and artificial ly ventilated rats pretreated either with ketanserin (5-HT2A/C antagonist; 2 mg/kg iv), 5-CT (5-HT1A/B agonist; 10 mu g/kg iv), or saline (sham). Rats were exposed to three 5-min episodes of hypoxia [fractional inspired O-2 ( FIO2) = 0.11], separated by 5 min of hyperoxia (FIO2 = 0.5). During hypoxia , ketanserin augmented phrenic but not hypoglossal burst amplitude; 5-CT ha d no effect. Both drugs accentuated PHFD. Ketanserin blocked phrenic LTF; h ypoglossal LTF was not apparent, even in sham-treated rats. 5-CT reversed L TF, resulting in a long-lasting depression of phrenic burst frequency and a mplitude without effect on hypoglossal burst amplitude. The data suggest th at 1) 5-HT2A/C receptor activation modulates the short-term hypoxic phrenic response and PHFD and is necessary for LTF; and 2) 5-CT may affect time-de pendent hypoxic ventilatory responses by reducing serotonin release via 5-H T1A/B autoreceptor activation.