Role of Purinergic and Nicotinic Receptors in the Hypoxia/Hypercapnia Evoked Excitation of Parasympathetic Cardiac Vagal Neurons in the Brainstem

AbstractHypoxia and hypercapnia are among the strongest challenges to the cardiorespiratory system, and these responses are altered by prenatal nicotine exposure. However the mechanism(s) responsible for these cardiorespiratory responses, and their alteration by prenatal nicotine exposure are unknown. We used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and synaptic neurotransmission to cardiac vagal neurons (CVNs) that control heart rate. Respiratory-related increases in excitatory neurotransmission only occurred upon recovery from hypoxia/hypercapnia in unexposed animals. These responses were mediated in part by purinergic receptors. Prenatal nicotine exposure transformed central cardiorespiratory responses; CVNs received a respiratory-related neurotransmission not during recovery but during hypoxia/hypercapnia which was wholly dependent upon nicotinic receptor activation. In the presence of nicotinic antagonists, the responses in prenatal nicotine animals reverted to the pattern of responses in unexposed animals. These data identify a new functional role for purinergic receptors in the cardiorespiratory responses to hypoxia/hypercapnia and their role in occluding nicotinic receptor activation with prenatal nicotine exposure. [Tzu Chi Med J 2008;20(1):1–10