Platelet-activating factor modulates cardiorespiratory responses in the conscious rat

respiratory responses in the conscious rat. Am. J. Physiol. 275 (Regulatory Integrative Comp. Physiol. 44): R604-R611, 1998.—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 dorsocau- dal brain stem were measured in unrestrained adult rats. mc-PAF elicited significant minute ventilation (VE) enhance- ments that were primarily due to tidal volume increases and were accompanied by respiratory alkalosis, heart rate in- crease, and reduction of arterial blood pressure. Such cardio- vascular and respiratory effects did not occur after administra- tion 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 VE from 120.4 6 7.5 to 204.6 6 11.4 ml/min in CO, after BN-52021, VE increased only from 118.7 6 6.9 to 137.3 6 8.9 ml/min (CO vs. BN-52021, P , 0.001). We conclude that PAFR activation in the dorsocaudal brain stem exerts significant cardioventila- tory effects during normoxia and appears to play an impor- tant modulatory role in the VE response to hypoxia in conscious rats. respiratory control; brain stem; hypoxia; hypercapnia; blood pressure; heart rate