Serotonin is necessary for short-term modulation of the exercise ventilatory response

Abstract

The exercise ventilatory response is augmented during conditios of increased respiratory dead space (ΔVd), a phenomenon that we refer to as short term modulation (STM). To test the hypothesis that serotonin is necessary in the mechanims underlying STM, experiments were conducted on ten awake goats. Ventilation, CO 2 production and Pa CO 2 were measured at rest and during treadmill exercise (4 km/h, 5% grade), with and without ΔVd (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 CO 2 decreased from rest to exercise to similar degree with (−1.9mmHg) and without (−1.8mmHg) ΔVd; (2) the exercise ventilatory response increased 59%±13% ( p<0.01) with ΔVd, accounting for similar exercise Pa CO 2 regulation and demonstrating STM; and (3) effects of ΔVd on exercise tidal volume and frequency responses were inconsistent. Post-methysergide: (1) there were no significant effects on ventilation or Pa CO 2 at rest or during exercise in control (mask) conditions; (2) the exercise ventilatory response was unaffected by ΔVd, thereby allowing Pa CO 2 to increase 4.1±3.0 mmHg from the rest to exercise ( P<0.05); and (3) with ΔVd 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 ΔVd was not affected further, allowing Pa CO 2 to increase form 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.