Platelet-activating factor modulates cardiorespiratory responses in the conscious rat

Platelet-activating factor receptor (PAFR) activation is associated with increases in neuronal excitability. We hypothesized that PAF may play a role in cardiorespiratory control. Ventilatory responses to microinjection of a long-acting PAF analog (mc-PAF, 1 μg in 1 μl) within the dorsocaudal brain stem were measured in unrestrained adult rats. mc-PAF elicited significant minute ventilation (V̇E) enhancements that were primarily due to tidal volume increases and were accompanied by respiratory alkalosis, heart rate increase, and reduction of arterial blood pressure. Such cardiovascular and respiratory effects did not occur after administration of either vehicle or the inactive analog lyso-PAF. The effect was blocked when animals were coadministered the presynaptic PAFR antagonist BN-52021 or recombinant PAF acetyl hydrolase. To determine the relative contribution of PAF to hypercapnic and hypoxic ventilation, microinjections were performed in additional animals with either vehicle (CO, 1 μl) or with 5 μg in 1 μl of BN-52021. Hypercapnic challenges with 5% CO₂ were unaffected by BN-52021. In contrast, although 10% O₂ breathing increased V̇E from 120.4 ± 7.5 to 204.6 ± 11.4 ml/min in CO, after BN-52021, V̇E increased only from 118.7 ± 6.9 to 137.3 ± 8.9 ml/min (CO vs. BN-52021, P < 0.001). We conclude that PAFR activation in the dorsocaudal brain stem exerts significant cardioventilatory effects during normoxia and appears to play an important modulatory role in the V̇E response to hypoxia in conscious rats.