Serotonin blockade augments the hypoxic ventilatory response in awake goats

Ventilatory acclimatization to hypoxia (VAH) is a time-dependent increase in ventilation during prolonged hypoxic exposure. In goats, VAH occurs within 4 h and is primarily mediated by an increasing sensitivity and output of the carotid body. Recent studies have indicated that serotonin (5-HT) is an important modulator of respiratory responses within the CNS. As 5-HT is also found within the carotid body, we hypothesized that 5-HT may be involved in the modulation of carotid body sensitivity during hypoxia and may therefore modulate VAH. To test this hypothesis, awake goats were given either methysergide (1 mg/kg iv) or saline (approx. 12-14 ml iv) 30 min prior to being exposed to 4 h of isocapnic hypoxia (PaO₂ = 40 torr). The goats were then allowed a minimum of 2 weeks before being tested again with the opposite injection (methysergide or saline). Goats given methysergide had a non-significant increase in mean PaCO₂ of 2 torr during normoxia but did not differ in their normoxic respiratory pattern from the controls. The acute hypoxic ventilatory response was significantly potentiated in the methysergide treated goats. Minute ventilation (V_E) was significantly elevated over the control response after 30 min and 60 min of hypoxic exposure. Although methysergide increased the acute hypoxic V_E response it did not alter the time dependent increase in V_E with prolonged hypoxic exposure. We conclude that 5-HT modulates the acute hypoxic ventilatory response in goats, but does not appear to be involved in VAH.