Platelet-activating factor (PAF) inhibition in the nucleus tractus solitarius (NTS) attenuates hypoxic ventilatory response in the conscious rat

Recent evidence suggests that PAF is a potent modulator of synaptic transmission, and in particular, of NMDA receptor-mediated neural events. To determine the relative contribution of PAF to the hypoxic ventilatory response in freely-behaving rats, microinjections to the commissural NTS were performed with either DMSO (CO; 1μL) or with 5 μg/1μL of BN52021, a pre-synaptic PAF inhibitor, in 5 chronically-instrumented adult Sprague-Dawley rats. Thirty min after injection, hypoxic ventilatory challenges (10% O₂) were administered, and V̇_E was measured by the barometric technique. Vehicle-treated animals increased V̇_E from 120.4±7.5 mL/min to 204.6±11.4 mL/min (p < 0.0001). In contrast, after BN52021, V̇_E increased from 118.7±6.9 mL/min to 137.3±8.9 mL/min (CO vs. BN52021: p < 0.001). When the microcannula was placed in the cerebellum (n=2), in the spinal cord caudal to the NTS (n=3). or in the cortex (n=2), no differences in V̇_E hypoxic responses occurred between vehicle and PAF antagonist treatments (p - NS). We conclude that PAF plays an important modulatory role in the ventilatory response to hypoxia.