Acute intermittent hypoxia increases both phrenic and sympathetic nerve activities in the rat

Abstract

The respiratory system expresses multiple forms of plasticity, defined as alterations in the breathing pattern that persist or develop after a stimulus. Stimulation of breathing with intermittent hypoxia (IH) elicits long-term facilitation (LTF), a type of plasticity in which respiratory motor activity progressively increases in anaesthetized animals, even after the stimuli have ceased and blood gases have normalized. It is unknown whether the sympathetic nervous system similarly expresses IH-induced plasticity, but we predicted that IH would evoke LTF in sympathetic nerve activity (SNA) because respiratory and sympathetic control systems are coupled. To test this idea, we recorded splanchnic (sSNA) and phrenic nerve activities (PNA) in equithesin-anaesthetized rats. Animals were exposed to 10 45 s episodes of 8% O 2 -92% N 2 , separated by 5 min intervals of 100% O 2 , and recordings were continued for 60 min following the last hypoxic exposure. Cycle-triggered averages of integrated PNA and sSNA from periods preceding, and 5 and 60 min following the hypoxic stimuli were compared. Intermittent hypoxia significantly increased both sSNA and PNA. Treatment with methysergide (3 mg kg −1 , I.V.) 20 min before the intermittent hypoxic exposures prevented the increases in integrated PNA and sSNA 60 min after IH, indicating a role of serotonergic pathways in this form of plasticity. No increases in PNA and sSNA occurred at comparable times (60 and 120 min) in rats not exposed to hypoxia. The increased sSNA was not simply tonic, but was correlated with respiratory bursts, and occurred predominantly during the first half of expiration. These findings support the hypothesis that sympathorespiratory coupling may underlie the sustained increase in SNA associated with the IH that occurs during sleep apnoea.

Carotid sinus nerve stimulation, but not intermittent hypoxia, induces respiratory LTF in adult rats exposed to neonatal intermittent hypoxia

“…LONG-TERM EFFECTS OF N-IH ON RESPIRATORY LTF phrenic nerve activity under hypercapnia (17), acute hypoxia (8), or following induction of phrenic LTF by IH (9). Accordingly, in control rats, phrenic LTF was accompanied by an enhanced sympathetic activity during expiration.…”

“…To take into account the entrainment of splanchnic nerve activity by the respiratory network (17,19,42,43), we also analyzed cycle-triggered histograms by dividing splanchnic activity according to the phase of the respiratory cycle into first and second halves of inspiration and first and second halves of expiration (8), such as previously used to demonstrate a coupling of splanchnic activity to phrenic LTF (9).…”

Contribution of Autonomic Nervous System to the Hypertension Induced by Obstructive Sleep Apnea

“…The autonomic alteration is characterized by an enhanced sympathetic outflow, reduction of the efficiency of the baroreflexes sensitivity and alterations of heart rate variability. Indeed, non-invasive spectral analysis of heart rate variability suggested a preponderance of the sympathetic drive in animals exposed to chronic intermittent hypoxia [15,20,57,86,88,92], similarly to what was observed patients with OSA [68,72,97,99]. Thus, it is likely that the enhanced sympathetic activity along with the reduction of the baroreflex sensitivity could impair heart rate variability and the regulation of vasomotor tone of blood vessels contributing to the hypertension.…”

“…Similarly, animals exposed to chronic intermittent hypoxia present enhanced sympathetic discharges and respiratory responses to acute hypoxia, and develop systemic hypertension [15,20,25,26,34,37,48,59,86,87,92,115]. The autonomic alteration is characterized by an enhanced sympathetic outflow, reduction of the efficiency of the baroreflexes sensitivity and alterations of heart rate variability.…”

Hypersensitivity of lung vagal C fibers induced by acute intermittent hypoxia in rats: role of reactive oxygen species and TRPA1

“…Thus, sensitization of LVCFs by inflammatory mediators may play an important role in the pathogenesis of airway hypersensitivity (31). Indeed, exposure to intermittent hypoxia increases breathing (16,27). However, exposure to intermittent hypoxia can also induce pathophysiological consequences, such as increased generation of reactive oxygen species (ROS) in airways by repeated hypoxia-reoxygenation cycles (8, 44) and several forms of neuroplasticity (35,41).…”