SEROTONIN IS NECESSARY FOR SHORT-TERM MODULATION OF THE EXERCISE VENTILATORY RESPONSE

The exercise ventilatory response is augmented during conditions of increased respiratory dead space (DELTAVd), a phenomenon that we refer to as short term modulation (STM). To test the hypothesis that serotonin is necessary in the mechanism underlying STM, experiments were conducted on ten awake goats. Ventilation, CO2 production and Pa(CO2) were measured at rest and during treadmill exercise (4 km/h, 5% grade), with and without DELTAVd (0.25 L), before and after systemic administration of the serotonin receptor antagonist, methysergide maleate (n = 6; 1 mg/kg, i.v.), or the tryptophan hydroxylase inhibitor, p-chlorophenylalanine (PCPA; n = 4; 100 mg/kg, i.v.). Pre-methysergide: (1) Pa(CO2) decreased from rest to exercise to a similar degree with (-1.9 mmHg) and without (-1.8 mmHg) DELTAVd; (2) the exercise ventilatory response increased 59% +/- 13% (P < 0.01) with DELTAVd, accounting for similar exercise Pa(CO2) regulation and demonstrating STM; and (3) effects of DELTAVd on exercise tidal volume and frequency responses were inconsistent. Post-methysergide: (1) there were no significant effects on ventilation or Pa(CO2) at rest or during exercise in control (mask) conditions; (2) the exercise ventilatory response was unaffected by DELTAVd, thereby allowing Pa(CO2) to increase 4.1 +/- 3.0 mmHg from rest to exercise (P < 0.05); and (3) with DELTAVd during exercise, the tidal volume response was increased, but was offset by a decreased frequency response. Following PCPA (16-24 h): (1) hyperventilation was evident at rest and during exercise; (2) the exercise ventilatory response was augmented, indicating STM; and (3) the exercise ventilatory response with DELTAVd was not affected further, allowing Pa(CO2) to increase from rest to exercise and indicating an inability to elicit further STM. These data suggest that serotonin is necessary for short term modulation of the exercise ventilatory response with increased respiratory dead space, although the location of relevant serotonin receptors is not yet clear.