Patients with sleep apnea, a sleep disorder characterized by intermittent episodes of hypoxia (CIH), are at an increased risk for cardiovascular problems. CIH leads to a long lasting augmentation of respiratory and sympathetic motor output after the cessation of CIH, a phenomena termed long-term facilitation (LTF). LTF is a serotonin dependent mechanism. Additionally, serotonergic neurons in the raphe nuclei receive dense projections from orexin (OX) neurons; thus OX may contribute to the development of LTF. Sleep apnea patients also exhibit increased arousals and micro-arousals; OX may play a role in this sleep fragmentation. Determining the mechanisms involved the development of hypertension following sleep apnea will allow for finding
…show more content…
Recent reports show OX knockout mice have a reduced ventilatory and phrenic LTF and repetitive hypoxic stimulation awakens the mice, similar to sleep apnea in humans. Focal administration of an OX1 antagonist in the RTN reduces the ventilatory response to 7% CO2 by ~30% in wakefulness. However, the involvement of OX receptors, specifically OX2, in the RTN on the blood pressure response to CO2 or hypoxia and in the development of sympathetic LTF is unknown. Additionally, there is conflicting evidence on the role of OX and OX receptors in blood pressure (BP) regulation. Reports show that blockade of OX receptor type 2 (OX2) in the rostral ventral lateral medulla (RVLM) reduces BP in spontaneously hypertensive rats (SHR) without affecting resting BP. However, humans with narcolepsy, a condition with reduced OX, have a reduced BP at rest. The sleep pattern of these patients exhibit increased arousals and micro-arousals. However, it is unknown whether increased medullary OX receptors is involved in the development of hypertension after …show more content…
the PVN and RTN. This may be accomplished by modulating Ih via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. While Ih typically generates an excitatory inward current at subthreshold voltages, several studies have reported that HCN channels on distal dendrites shunt synaptic inputs, thus reducing neuronal excitability. For instance, reports show OX inhibition of HCN channels in the prefrontal cortex increases neuronal excitability. OX may modulate Ih within cardiorespiratory or arousal centers in a similar fashion, leading to CIH induced
Recent reports show OX knockout mice have a reduced ventilatory and phrenic LTF and repetitive hypoxic stimulation awakens the mice, similar to sleep apnea in humans. Focal administration of an OX1 antagonist in the RTN reduces the ventilatory response to 7% CO2 by ~30% in wakefulness. However, the involvement of OX receptors, specifically OX2, in the RTN on the blood pressure response to CO2 or hypoxia and in the development of sympathetic LTF is unknown. Additionally, there is conflicting evidence on the role of OX and OX receptors in blood pressure (BP) regulation. Reports show that blockade of OX receptor type 2 (OX2) in the rostral ventral lateral medulla (RVLM) reduces BP in spontaneously hypertensive rats (SHR) without affecting resting BP. However, humans with narcolepsy, a condition with reduced OX, have a reduced BP at rest. The sleep pattern of these patients exhibit increased arousals and micro-arousals. However, it is unknown whether increased medullary OX receptors is involved in the development of hypertension after …show more content…
the PVN and RTN. This may be accomplished by modulating Ih via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. While Ih typically generates an excitatory inward current at subthreshold voltages, several studies have reported that HCN channels on distal dendrites shunt synaptic inputs, thus reducing neuronal excitability. For instance, reports show OX inhibition of HCN channels in the prefrontal cortex increases neuronal excitability. OX may modulate Ih within cardiorespiratory or arousal centers in a similar fashion, leading to CIH induced