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

Am J Physiol. 1999 Sep;277(3):R658-66. doi: 10.1152/ajpregu.1999.277.3.R658.


We hypothesized that the 5-hydroxytryptamine (5-HT) active drugs ketanserin and 5-carboxamidotryptamine (5-CT) would modulate time-dependent hypoxic phrenic and hypoglossal responses, including 1) short-term hypoxic response, 2) posthypoxia frequency decline (PHFD), and 3) long-term facilitation (LTF) of respiratory motor output. Phrenic and hypoglossal nerve activities were recorded in urethan-anesthetized, paralyzed, vagotomized, and artificially ventilated rats pretreated either with ketanserin (5-HT(2A/C) antagonist; 2 mg/kg iv), 5-CT (5-HT(1A/B) agonist; 10 microg/kg iv), or saline (sham). Rats were exposed to three 5-min episodes of hypoxia [fractional inspired O(2) (FI(O2)) = 0.11], separated by 5 min of hyperoxia (FI(O2) = 0.5). During hypoxia, ketanserin augmented phrenic but not hypoglossal burst amplitude; 5-CT had no effect. Both drugs accentuated PHFD. Ketanserin blocked phrenic LTF; hypoglossal LTF was not apparent, even in sham-treated rats. 5-CT reversed LTF, resulting in a long-lasting depression of phrenic burst frequency and amplitude without effect on hypoglossal burst amplitude. The data suggest that 1) 5-HT(2A/C) receptor activation modulates the short-term hypoxic phrenic response and PHFD and is necessary for LTF; and 2) 5-CT may affect time-dependent hypoxic ventilatory responses by reducing serotonin release via 5-HT(1A/B) autoreceptor activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Hypoxia / physiopathology*
  • Ketanserin / pharmacology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / physiology
  • Respiratory Mechanics / drug effects*
  • Respiratory Mechanics / physiology
  • Serotonin / analogs & derivatives*
  • Serotonin / pharmacology
  • Serotonin Receptor Agonists / pharmacology*
  • Time Factors


  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Serotonin
  • 5-carboxamidotryptamine
  • Ketanserin