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 response, a response known as short-term modulation (STM). We hypothesized that STM results from a spinal, serotonin (5-HT)-dependent mechanism. Because 5-HT(1A) autoreceptors on caudal brain stem raphe neurons inhibit 5-HT release, we hypothesized that 5-HT(1A)-receptor agonists would inhibit, whereas 5-HT(1A)-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-HT(1A)-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 mg/kg) or the antagonist 4-iodo-N-(2-[4-(methoxyphenyl)-1-piperazinyl]ethyl)-N-2-pyridinylbenz amide (MPPI; 0.08 mg/kg). 8-OH-DPAT increased the slope of the arterial PCO(2) vs. metabolic CO(2) production relationship and decreased the ventilation vs. metabolic CO(2) production relationship during exercise with increased dead space (not with the mask alone), indicating an impairment 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 serotonergic neurons and 5-HT release.
Henderson
D R
DR
Department of Comparative Biosciences, Division of Science and Math, University of Wisconsin, Madison, Wisconsin 53706, USA. hendersn@centre.edu
Mitchell
G S
GS
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D005260:Female; D006041:Goats / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology*; D012123:Pulmonary Ventilation / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
C416045:4-iodo-N-(2-(4-(methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinylbenzamide; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D002245:Carbon Dioxide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin