Spinal serotonin receptor activation modulates the exercise ventilatory response with increased dead space in goats

Small increases in respiratory dead space (VD) augment the exercise ventilatory response by a serotonin-dependent mechanism known as short-term modulation (STM). We tested the hypotheses that the relevant serotonin receptors for STM are in the spinal cord, and are of the 5-HT2-receptor subtype. After preparing adult female goats with a mid-thoracic (T6-T8) subarachnoid catheter, ventilation and arterial blood gases were measured at rest and during treadmill exercise (4.8 km/h; 5% grade) with and without an increased VD (0.2-0.3 L). Measurements were made before and after spinal or intravenous administration of a broad-spectrum serotonin receptor antagonist (methysergide, 1-2 mg total) and a selective 5-HT2-receptor antagonist (ketanserin, 5-12 mg total). Although spinal methysergide had no effect on the exercise ventilatory response in control conditions, the augmented response with increased VD was impaired, allowing PaCO2 to increase from rest to exercise. Spinal methysergide diminished both mean inspiratory flow and frequency responses to exercise with increased VD. Spinal ketanserin impaired PaCO2 regulation with increased VD, although its ventilatory effects were less clear. Intrathecal dye injections indicated CSF drug distribution was caudal to the upper cervical spinal cord and intravenous drugs at the same total dose did not affect STM. We conclude that spinal 5-HT2 receptors modulate the exercise ventilatory response with increased VD in goats.