Short-term modulation of the exercise ventilatory response in goats: effects of 8-OH-DPAT and MPPI

Increased respiratory dead space increases the exercise ventilatory respons e, a response known as short-term modulation (STM). We hypothesized that ST M results from a spinal, serotonin (5-HT)-dependent mechanism. Because 5-HT 1A autoreceptors on caudal brain stem raphe neurons inhibit 5-HT release, w e hypothesized that 5-HT1A-receptor agonists would inhibit, whereas 5-HT1A- receptor antagonists would enhance, STM. Ventilatory and arterial blood-gas measurements were made at rest and during exercise (4.0-4.5 km/h, 5% grade ) in goats with the respiratory mask alone or with increased dead space (0. 20-0.25 liter), before and after intravenous administration of the 5-HT1A-r eceptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 mg/k g) or the antagonist 4-iodo-N-{2-[4-(methoxyphenyl)-1-piperazinyl] ethyl}-N -2-pyridinylbenzamide (MPPI; 0.08 mg/kg). 8-OH-DPAT increased the slope of the arterial Pco(2) vs. metabolic CO2 production relationship and decreased the ventilation vs. metabolic CO2 production relationship during exercise with increased dead space (not with the mask alone), indicating an impairme nt of STM. In contrast, MPPI had minimal effects on any measured variable. Although nonspecific effects of 8-OH-DPAT cannot be ruled out, impaired STM is consistent with the hypothesis that STM requires active raphe serotoner gic neurons and 5-HT release.